PET-RAFT Polymerization：Catalyst and Its Application in Biomedicine and Advanced Manufacturing

Yuxiang Zhang; Weijie Zhang; Lei Liu; Yirui Huang; Hui Wang; Anchao Feng

doi:10.7536/PC241013

Progress in Chemistry ›› 2025, Vol. 37 ›› Issue (8) : 1105-1116 DOI: 10.7536/PC241013

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PET-RAFT Polymerization：Catalyst and Its Application in Biomedicine and Advanced Manufacturing

Yuxiang Zhang ¹^,²
, Weijie Zhang ¹^,²
, Lei Liu ¹^,²
, Yirui Huang ³
, Hui Wang ³^,^*
, Anchao Feng ¹^,²^,^*

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Abstract

PET-RAFT polymerization （Photoinduced Electron Transfer-Reversible Addition-Fragmentation Chain Transfer Polymerization） has been widely concerned and applied in the field of polymerization due to its characteristics such as low energy consumption，mild reaction conditions，time-space control，reaction orthogonality and oxygen resistance. In terms of surface modification，PET-RAFT polymerization is used to improve the surface characteristics of materials，such as biocompatibility and anti-adhesion. In the biomedical field，PET-RAFT polymerization technology is used to prepare drug delivery systems such as spherical micelles and vesicles. In addition，the application of PET-RAFT polymerization in 3D printing and laser writing demonstrates its great potential for precise control of material structure and functionalization. The key to PET-RAFT polymerization is to find suitable photocatalysts. Currently，the types of catalysts include homogeneous catalyst systems，such as transition metal complexes，porphyrin and phthalocyanine catalysts，organic dyes，and semiconductor materials，as well as heterogeneous catalyst systems，such as macro material supported，nano material supported，metal organic framework，covalent organic framework，conjugated microporous polymers，etc. Among them，heterogeneous catalysts can be effectively recovered and utilized by centrifugation and filtration separation of photocatalysts. The heterogeneous catalyst can be effectively recycled by centrifugation and filtration separation. In the future，researchers will develop new low cost，high efficiency，easy recovery，non-toxic photocatalysts to improve the use of low energy photons and improve the compatibility of photopolymerization with the environment.

Contents

1 Introduction

2 Polymerization properties of PET-RAFT

3 Homogenous photocatalysts for PET-RAFT

3.1 Transition metal complexs

3.2 Porphyrin and Phthalocyanine catalysts

3.3 Organic dyes

3.4 Semiconductor materials

4 Heterogeneous photocatalysts for PET-RAFT

5 Application of PET-RAFT polymerization

5.1 Surface modification

5.2 Biomedical application

5.3 3D printing and laser writing

6 Conclusion and outlook

Graphical abstract

Keywords

PET-RAFT polymerization / photocatalytic system / surface modification / biomedicine / 3D printing

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Yuxiang Zhang, Weijie Zhang, Lei Liu, Yirui Huang, Hui Wang, Anchao Feng. PET-RAFT Polymerization：Catalyst and Its Application in Biomedicine and Advanced Manufacturing. Progress in Chemistry, 2025, 37(8): 1105-1116 DOI:10.7536/PC241013

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1 Introduction

Free radical polymerization proceeds rapidly, but it is prone to bimolecular termination within the polymerization system, making it difficult to control the molecular weight and molecular weight distribution of the resulting polymers. Therefore, scientists have proposed the concept of Reversible-Deactivation Radical Polymerization (RDRP) to precisely control polymer synthesis. Currently, the most extensively studied RDRP methods include Nitroxide-Mediated Living Free-Radical Polymerization (NMP), Atomic Transfer Radical Polymerization (ATRP), and Reversible Addition-Fragmentation Chain Transfer Polymerization (RAFT). The key to these methods lies in reducing the concentration of free radicals in the polymerization system, thereby suppressing side reactions such as bimolecular termination. Among them, RAFT polymerization has gained wider application due to its high efficiency and versatility. Compared with traditional thermal-initiated RAFT polymerization, light-mediated RAFT polymerization offers advantages such as abundant, readily available, and highly sustainable light sources. According to the polymerization mechanism, light-mediated RAFT polymerization can be classified into: (1) photolysis-based RAFT polymerization; (2) RAFT polymerization initiated by externally added photoinitiators; and (3) PET-RAFT polymerization. PET-RAFT stands out for its low energy consumption, simple reaction setup, and fewer side reactions, making it a viable alternative to conventional initiation methods^[1-2]. In 2014, Boyer's research group^[3]first introduced the concept of PET-RAFT polymerization, using Ir(ppy)₃as a photocatalyst to catalyze the polymerization of various vinyl monomers, yielding homopolymers with relatively narrow molecular weight distributions (M _w/M _n<1.3). The introduction of PET-RAFT polymerization has significantly advanced the development of RDRP. The current explanation of the PET-RAFT polymerization mechanism is illustrated in Figure 1: an external light source irradiates the photocatalyst, causing it to transition from the ground state to the excited state. The excited-state photocatalyst then undergoes electron or energy transfer with the RAFT chain transfer agent, ultimately generating free radicals that initiate polymerization in the system. A distinctive feature of PET-RAFT polymerization is that the RAFT reagent serves simultaneously as both a photoinitiator and a chain transfer agent during the reaction. Current research on PET-RAFT polymerization primarily focuses on two aspects: the photocatalysts used in the polymerization process and their application areas.

Compared with other active radical polymerizations, PET-RAFT polymerization not only features low energy consumption, mild reaction conditions, controllable time and space, and adjustable polymerization rates, but also attracts attention due to its unique high oxygen tolerance and catalyst diversity. In recent years, as more and more photocatalysts have been discovered, the application scope of PET-RAFT polymerization technology has continued to expand. This review will primarily focus on three aspects: the polymerization characteristics of PET-RAFT, types of photocatalysts, and polymerization applications.

2 Polymerization characteristics of PET-RAFT

PET-RAFT polymerization has a wide range of applications due to its excellent polymerization characteristics, including oxygen tolerance, good spatiotemporal control, reaction orthogonality, and a broad wavelength range.

The oxygen tolerance of PET-RAFT polymerization is closely related not only to the catalyst but also to the co-catalyst and solvent. In PET-RAFT polymerization, the choice of catalyst significantly influences the oxygen tolerance of the polymerization system. The Boyer group^[3]used Ir(ppy)₃as a photocatalyst to investigate the PET-RAFT polymerization of acrylate and acrylamide monomers without prior deoxygenation. The results showed that Ir(ppy)₃acts as both a photocatalyst to mediate polymerization and a reducer of oxygen in the system. Even under aerobic conditions, the polymer molecular weight distribution Đcould be maintained below 1.3, demonstrating that this RAFT polymerization exhibits a certain degree of oxygen tolerance. Furthermore, the Boyer group^[4]found in subsequent studies that replacing Ir(ppy)₃with the water-soluble photocatalyst Ru(bpy)₃Cl₂allowed Ru(bpy)₃Cl₂-mediated PET-RAFT polymerization to synthesize higher-order multiblock copolymers without the need for deoxygenation. In 2015, the Boyer group^[5]also revealed that zinc tetraphenylporphyrin ZnTPP, in addition to its photocatalytic properties, can reduce triplet oxygen³O from the environment into singlet oxygen¹O, which can be removed by the solvent DMSO. The oxygen tolerance of the reaction depends on the quantum yield of the photocatalyst in reducing triplet oxygen³O to singlet oxygen¹O. Besides the hydrophobic photocatalyst zinc tetraphenylporphyrin ZnTPP, other porphyrins have also been shown to exhibit high oxygen tolerance under aqueous conditions. For example, the Boyer group^[6]demonstrated that the tetrasulfonate derivative of ZnTPP (ZnTPPS^4-) can achieve oxygen-tolerant PET-RAFT polymerization in water. Additionally, metal-free catalysts such as Eosin Y (EY), when combined with tertiary amine reducing agents, also exhibit oxygen tolerance in PET-RAFT polymerization^{[7- 8]}. The role of co-catalysts in enhancing the oxygen tolerance of PET-RAFT polymerization is primarily achieved by capturing oxygen or neutralizing reactive oxygen species. For instance, triethylamine can rapidly react with oxygen to form imine or hydroxylamine intermediates, effectively reducing the quenching effect of oxygen and improving polymerization efficiency. The choice of solvent is crucial for the oxygen tolerance of PET-RAFT polymerization, with solvent polarity, oxygen solubility, and their synergistic effects with the reaction system being key factors. Polar solvents such as DMSO can react with singlet oxygen to form sulfoxides, thereby effectively removing oxygen; while water, as a solvent, further reduces the inhibitory effect of oxygen on polymerization due to its lower oxygen solubility. Nonpolar solvents like toluene have higher oxygen solubility, but with the synergistic action of efficient catalysts and co-catalysts, a certain degree of oxygen tolerance can still be achieved. The oxygen tolerance of PET-RAFT polymerization is determined by the synergistic effects of multiple factors, including photocatalysts, co-catalysts, and solvents. By selecting efficient photocatalysts, appropriately using co-catalysts, and optimizing the solvent system, the oxygen tolerance of the polymerization system can be significantly improved, providing strong support for the application of PET-RAFT polymerization technology in complex environments.

PET-RAFT polymerization's high oxygen tolerance allows the polymerization system to operate without deoxygenation, making it suitable for applications such as flow reactors, high-throughput synthesis, and self-healing materials. Boyer's research group^[9]installed cotton threads loaded with photocatalysts inside a spiral tubular reactor, successfully achieving PET-RAFT polymerization in a flowing process. This innovative setup significantly enhanced the polymerization rate. The combination of a flow reactor with photocatalysis ensured more uniform illumination throughout the reactor, reducing side reactions and facilitating the synthesis of compounds with precise structures. The oxygen tolerance of PET-RAFT polymerization can be utilized in high-throughput methods to synthesize various small-volume polymers, further aiding in elucidating the relationship between polymer structure and properties. In 2019, Boyer's research group^[10]applied PET-RAFT polymerization to high-throughput synthesis, preparing an antibacterial polymer library containing 120 different polymers in a 96-well microtiter plate, and screened out truly useful antibacterial compounds from it, as shown in Figure 2. The oxygen tolerance of PET-RAFT polymerization gives it an advantage in the preparation of self-healing materials.

PET-RAFT polymerization exhibits excellent spatiotemporal control, allowing the polymerization reaction to be initiated or terminated by simply turning the light source on or off. Compared to thermal polymerization, which can only regulate the polymerization rate through temperature, photopolymerization offers a broader range of control methods, enabling rate modulation via temperature, dosage of photoinitiators or photocatalysts, and adjustment of light intensity and wavelength, thus further expanding its temporal and spatial applications. When a chemical reaction can proceed independently without affecting other reactions within the same reaction system, it is referred to as orthogonal to another reaction^[12]. Given that different structured photocatalysts absorb light over varying wavelength ranges, PET-RAFT polymerization possesses unique orthogonality, enabling multiple non-interfering chemical reactions to occur simultaneously within the same reaction system^[13-18]. The Boyer group^[19]prepared polymers with specific structures by switching between red and green light. First, under red light irradiation, pheoA selectively activated the dithiobenzoate RAFT agent, synthesizing a linear copolymer bearing trithiocarbonate side groups. Subsequently, under green light irradiation, the ZnTPP photocatalyst activated the trithiocarbonate side groups, and by controlling the duration of illumination at different wavelengths, graft copolymers with tailored molecular weights and side-chain lengths were synthesized. Furthermore, the orthogonality of this chemical reaction allows light irradiation to be combined with various external stimuli, including heat^[20], pH changes^[21], and electrochemistry^[22], enabling multi-switch control mechanisms and demonstrating great potential in various emerging fields.

Another significant advantage of PET-RAFT polymerization lies in its broad applicability across different wavelength ranges, enabling active polymerization controlled by visible and infrared light of various bands. The superior tissue penetration capability of near-infrared (NIR) light has been well established, and using NIR light to initiate polymerization can extend the application scope of PET-RAFT into the biomedical field. In 2019, Boyer and his research team^[23]conducted innovative research, employing aluminum phthalocyanine and aluminum naphthalocyanine as photocatalysts (PC) to achieve PET-RAFT polymerization mediated by far-red light (l=680 nm) and near-infrared light (l=780 nm and 850 nm), demonstrating that the reaction could achieve high conversion rates even when conducted through barriers such as paper, chicken skin, and pig skin, as shown in Figure 3. In 2020, Qiao and his colleagues^[24]reported a new research finding, using a metal-free self-assembled carboxylated porphyrin photocatalyst (SA-TCPP) as the photocatalyst to successfully achieve PET-RAFT polymerization in cell culture media under near-infrared light. PEGMA monomers were successfully polymerized at the microscale level within intact cell culture media, coexisting with mammalian cells. In 2023, Cheng et al.^[25]designed and synthesized a series of β-tetrasubstituted water-soluble zinc phthalocyanines (β-TS-Zns) as photocatalysts, performing PET-RAFT polymerization in aqueous systems at room temperature under near-infrared light irradiation (λ_max=730 nm). These preliminary results suggest that the biocompatible NIR-mediated PET-RAFT polymerization technology holds great promise for widespread applications in the biomedical field.

3 Homogeneous photocatalyst for PET-RAFT

3.1 Transition Metal Complexes

In 2014, Boyer's research group^[3]first proposed the concept of PET-RAFT. They used Ir(ppy)₃as a photocatalyst to initiate the polymerization of vinyl monomers under 450 nm blue light irradiation. Subsequently, they further demonstrated that the ruthenium compound Ru(bpy)₃Cl₂exhibits catalytic properties similar to those of iridium compounds^[4]. Since then, iridium and ruthenium polypyridine complexes, such as Ir(ppy)₃and Ru(bpy)₃Cl₂, have become the most commonly used rare transition metal complex catalysts in visible-light-mediated polymerization. A significant advantage of these rare transition metal complex catalysts is their exceptionally high catalytic activity, requiring only trace amounts (in the ppm range) to achieve excellent catalytic performance.

In summary, existing scoring systems have limited predictive capabilities for bleeding events, and their results are inconsistent^[25,30,33].

3.2 Porphyrin and Phthalocyanine Catalysts

Compared with transition metal catalysts, porphyrin-based catalysts are not only cheaper but also have a broader absorption wavelength range. Chlorophyll is the most abundant natural porphyrin catalyst found in nature. In 2014, Boyer's research group^[28]first utilized chlorophyll a (Chl a) extracted from spinach to catalyze PET-RAFT polymerization of acrylic and acrylamide monomers under low-energy infrared light, effectively avoiding side reactions caused by high-energy blue and ultraviolet light irradiation (Figure 4a). The success of this experiment also marked chlorophyll a (Chl a) as the first non-transition-metal-based photocatalyst. In 2015, Boyer's team^[5]used zinc tetraphenylporphyrin ZnTPP as a photocatalyst, with DMSO as the solvent, to investigate PET-RAFT polymerization of acrylic and acrylamide monomers under non-deoxygenated conditions. In addition to its photocatalytic properties, ZnTPP can also reduce triplet oxygen³O in the environment to singlet oxygen¹O, which can be removed by the solvent DMSO, making the reaction resistant to oxygen. To better adapt to biological conditions for RAFT photopolymerization, in 2016, Boyer's research group^[6]developed a water-soluble zinc porphyrin photocatalyst (ZnTPPS^4-), enabling rapid polymerization in non-deoxygenated aqueous systems. In the same year, Boyer's research group^[29]also used another biological photocatalyst, bacterial chlorophyll a (Bachl a), to catalyze polymerization, extending the PET-RAFT photopolymerization light range to 780~850 nm (Figure 4b). In 2021, Boyer's research group^[30]found that tetraphenylporphyrin (TPP), a metal-free compound similar in structure to zinc tetraphenylporphyrin ZnTPP, also possesses the ability to catalyze PET-RAFT polymerization, but requires the addition of a tertiary amine as a co-catalyst. These pioneering works have drawn increasing attention to porphyrin-based catalysts. Kowollik et al.^[31]used ZnTPP as a photocatalyst and designed orthogonal light sources with two different wavelengths to obtain block polymers with distinct structures. Chapman's research group^[32]prepared various star-shaped polymers via PET-RAFT polymerization mediated by ZnTPP as a photocatalyst and conventional thermal polymerization initiated by AIBN, comparing the mechanisms of traditional thermal-mediated and novel photo-mediated polymerizations. They found that the molecular weight distribution of polymers obtained through photo-mediated polymerization was significantly narrower (Figure 4c). Additionally, pheophorbide a (PheoA), an organic porphyrin derived from chlorophyll degradation and devoid of any metal center, has also been used in PET-RAFT polymerization studies, exhibiting high catalytic efficiency when combined with dithiobenzoate 4-cyanopentanedithioate (CPADB) in the system.

Metal phthalocyanines are artificially synthesized compounds with conjugated cyclic structures comparable in size to metal porphyrins. However, due to their inferior catalytic ability for PET-RAFT polymerization compared to metal porphyrins, their applications in the field of photocatalysis remain limited^[30].In 2021, Boyer and his colleagues^[30]employed NIR-mediated porphyrins and phthalocyanines as photocatalysts, supplemented by triethylamine (TEA) as a co-catalyst to facilitate thermodynamically favorable electron transfer. This strategy enabled the polymerization reaction to proceed smoothly in non-deoxygenated systems. Although porphyrin and phthalocyanine catalysts hold great potential in PET-RAFT polymerization, further optimization is still needed in terms of stability, catalytic efficiency, and environmental friendliness. Future research should focus on developing low-cost, highly efficient, and recyclable catalysts, expanding the spectral range into the near-infrared region, and exploring green synthesis methods and heterogeneous catalytic applications for these catalysts. Such improvements will further promote the widespread application of porphyrin and phthalocyanine catalysts in biomedicine, surface modification, and advanced manufacturing. For instance, Zhang et al.^[33]designed and synthesized a bimetallic porphyrin-based metal-organic framework (Bi-P(Co)MOF), successfully developing a red-light-responsive photocatalyst. This catalyst demonstrated excellent catalytic performance in the heterogeneous reduction of nitro compounds, combining high efficiency with environmental friendliness. This green photocatalyst showcases significant potential in both academic research and industrial applications.

3.3 Organic dyes

To make the reaction greener and more environmentally friendly, some metal-free organic photocatalysts have begun to be used in PET-RAFT polymerization. In 2017, Johnson's team^[34]reported a PET-RAFT reaction using the phenothiazine derivative 10-PTH (10-phenothiazine derivative) as a photocatalyst to insert N-isopropyl acrylamide into a parent polymer network containing trithiocarbonate. Since then, a series of phenothiazine-based photocatalysts have been successively developed^[35]. Liu et al.^[36]further innovated by combining a phenothiazine luminescent group with a phenyl acetyl salt to create a new polymer (P-PTh), which was found to initiate both radical and cationic photopolymerization across the entire wavelength range. The use of metal-free organic photocatalysts effectively avoids the issue of metal residues associated with traditional metal catalysts, creating favorable conditions for the application of the resulting products in electronics, biology, and medicine.

Rose Bengal Y, a common organic dye free from metal contamination, is typically used in the field of fluorescence research^[37]. In 2015, Boyer's research group^[7]conducted a series of PET-RAFT polymerization experiments using organic dyes such as methylene blue, fluorescein, rhodamine, and Rose Bengal Y as photocatalysts, investigating the polymerization of monomers including glycidyl methacrylate (GMA), HEMA, OEGMA, MAA, and HPMA. The experimental results indicated that Rose Bengal Y and fluorescein are effective catalysts for PET-RAFT polymerization. In both organic and aqueous environments, Rose Bengal Y can catalyze the PET-RAFT polymerization of various monomers with an extremely low catalyst loading (10 ppm)^[38]. Additionally, Rose Bengal Y exhibits good biocompatibility^[39], which has facilitated its widespread application in biomedical fields based on PET-RAFT polymerization mediated by Rose Bengal Y as a photocatalyst. In 2023, Arno et al.^[11]successfully prepared cell scaffolds with high biocompatibility and self-healing properties under visible light (450 nm) using Rose Bengal Y, a photocatalyst with excellent cell compatibility. However, organic dye catalysts are prone to photobleaching under prolonged illumination, leading to reduced catalytic activity and consequently affecting polymerization efficiency and catalytic cycling performance. This drawback not only lowers synthesis efficiency but also poses challenges for the secondary utilization of the catalyst. To address this issue, researchers have proposed various improvement strategies to enhance the stability of organic dye catalysts. First, immobilizing organic dyes onto solid supports (such as silica or polymer scaffolds) is an effective approach to reduce photobleaching. This immobilization method restricts dye molecular motion through physical or chemical interactions, thereby decreasing the likelihood of photobleaching. Second, introducing antioxidant groups (such as phenolic compounds) into the dye molecular structure or designing large conjugated systems can significantly enhance dye stability. Furthermore, optimizing the solvent environment can also minimize photobleaching, particularly by avoiding highly polar solvents that may accelerate the photobleaching process.

3.4 Semiconductor materials

With the continuous evolution and development of the photocatalysis field, semiconductor materials such as perovskite nanocrystals^[40]and graphitic carbon nitride^[41]have gradually come into people's view. Early studies have shown that certain metal oxide nanoparticles, such as TiO₂^[42]and ZnO^[43], can serve as photocatalysts for RAFT polymerization. However, these catalysts require high-energy ultraviolet light for initiation, which limits their widespread application. In 2017, Wang et al.^[44]reported an oxygen-tolerant and recyclable graphitic carbon nitride photocatalyst for PET-RAFT polymerization. This catalyst successfully catalyzed the polymerization of methyl methacrylate monomers under blue-light LED irradiation and could be reused at least seven times after recovery.

In recent years, with the deepening research on perovskites in the field of photocatalysis, attempts have been made to apply them to photocatalytic polymerization reactions, and preliminary successes have already been achieved. In 2022, the Egap team^[40]first introduced the use of all-inorganic lead halide perovskite CsPbBr₃nanocrystals as photocatalysts for PET-RAFT polymerization. The polymerization mechanism is illustrated in Figure 5a. They successfully polymerized acrylate monomers using excitation sources of different wavelengths (460~635 nm), and the study demonstrated that this polymerization exhibited "active and controlled" characteristics, with the resulting polymers showing a narrow molecular weight distribution maintained around 1.10. Titanium dioxide, a semiconductor metal oxide, is widely used in photovoltaic cells, organic synthesis, and other fields due to its excellent photoelectric conversion performance, and it can be easily recovered simply by filtration. In 2023, Bellotti et al.^[45]reported research results on N-doped TiO₂as a catalyst, achieving PET-RAFT polymerization under low-energy blue light conditions (Figure 5b). D-A conjugated organic polymers (COPs) are a new class of organic semiconductor photocatalytic materials, formed by alternating condensation of electron donor and acceptor units. In 2023, Hou et al.^[46]introduced CN absorption groups onto benzene rings, constructing a series of D-A conjugated organic polymers (COPs), which successfully catalyzed methyl methacrylate polymerization via PET-RAFT under white light irradiation (Figure 5c). The study confirmed that D-A conjugated organic polymers composed of relatively weak donor units and strong acceptor units are more conducive to photogenerated charge transfer, thereby exhibiting superior photocatalytic activity. Semiconductor photocatalysts, owing to their broad spectral response range and excellent catalytic performance, hold significant research value in the field of photocatalysis. However, their practical applications are often limited by stability issues. The main stability challenges include: (1) photocorrosion, where semiconductor materials are prone to photoinduced degradation during photocatalytic reactions, leading to a significant reduction in activity; (2) environmental sensitivity, as certain semiconductors (such as sulfides and halides) are highly sensitive to humidity and oxygen, easily undergoing oxidation or hydrolysis in air; (3) interfacial failure, where defects may form at the interface between the photocatalyst and the reaction medium, or the interface may become covered by byproducts, significantly affecting catalytic efficiency. To address these issues, researchers have proposed various optimization strategies to enhance the stability and performance of semiconductor photocatalysts: (1) surface modification and coating—applying protective layers (such as silica, titanium dioxide, polymers, or small organic molecules) onto the semiconductor surface can effectively isolate environmental factors, reduce photocorrosion, and optimize interfacial electron transfer efficiency, thereby improving photocatalytic performance; (2) development of wide-bandgap materials—selecting wide-bandgap semiconductors (such as TiO₂ and ZnO) or adjusting the bandgap structure through ion doping can effectively enhance material stability and extend its spectral response range into the visible or even near-infrared region; (3) nanostructure optimization—designing nanostructures with high specific surface areas and excellent light-harvesting capabilities (such as porous materials or heterojunctions) can significantly enhance the separation efficiency of photogenerated charges and improve catalytic performance; (4) composite material construction—combining with highly stable materials (such as noble metal nanoparticles or graphene) to create synergistic heterostructures not only improves material stability but also enhances resistance to photocorrosion and catalytic performance.

4 Heterogeneous photocatalyst for PET-RAFT

Photocatalysts can be attached to solid supports through physical adsorption, covalent bonding, reversible hydrogen bonding, and other methods, forming heterogeneous catalytic systems. Compared to homogeneous catalytic systems, heterogeneous catalysts allow for effective recovery of photocatalysts via centrifugation and filtration, enabling their recycling. Common support types include macro-material-supported, nano-material-supported, metal-organic framework-supported, covalent organic framework-supported, and conjugated microporous polymer-supported systems. (1) Macro-material-supported type. In 2018, Boyer's group loaded the catalyst zinc tetraphenylporphyrin ZnTPP onto cotton threads^[9]or cellulose^[47]for PET-RAFT reactions, allowing the catalyst to be easily recovered by simple washing. (2) Nano-material-supported type. In the same year, Boyer's group^[48]combined EY with silica nanoparticles (EY-SNP) as a photocatalyst, effectively enhancing the photodegradation stability of EY, as shown in Figure 6. In 2022, Pester et al.^[49]loaded fluorescein photocatalyst onto the surface of polymer-brush-functionalized micron-sized glass beads to form a multiphase photocatalyst PC@SiO₂. The transparent SiO₂ carrier at the micrometer scale ensures light penetration throughout the reaction mixture, allowing multiple polymerization cycles under mild reaction conditions, while the catalyst can be completely recovered simply by filtration. Moreover, this multiphase catalyst retains high catalytic efficiency even after several months of storage. (3) Covalent organic framework-supported type. In 2022, Xiao et al.^[46]loaded the photocatalyst zinc tetraphenylporphyrin ZnTPP into covalent organic frameworks (COFs) as a multiphase catalyst for PET-RAFT polymerization. Results showed that the polymerization reaction exhibited excellent controllability in the presence of oxygen and triethylamine (TEA), yielding polymers with narrow molecular weight distributions. (4) Metal-organic framework-supported type. In 2022, Lu's group^[50]encapsulated CsPbI₃nanocrystals within porphyrin Zr-MOF to obtain CsPbI₃@PCN-222, which was used as a photocatalyst to achieve PET-RAFT polymerization in various solvents, demonstrating high efficiency and good characteristics of narrow polymer molecular weight distribution. (5) Conjugated microporous polymer type. In 2023, Li et al.^[51]prepared silica nanorods via Sonogashira-Hagihara cross-coupling polymerization, followed by etching of their inner cores to obtain conjugated microporous polymer nanotubes CMPs with hollow nanostructures and highly porous architectures. The heterogeneous catalyst formed by loading Pd(PPh₃)₄ and CuI onto these conjugated microporous polymer CMPs features a large surface area, numerous active sites, high catalytic efficiency, and ease of separation, thus enabling the catalyst to be recycled repeatedly.

5 Applications of PET-RAFT Polymerization

5.1 Surface modification

Surface modification is a method for preparing novel materials with enhanced performance^[52-54]. By performing photopolymerization on the material surface, properties such as adhesion, wettability, and biocompatibility can be effectively improved^[55]. Due to its excellent polymerization characteristics, including oxygen tolerance, orthogonality, and mild reaction conditions, PET-RAFT has been widely applied in surface modification technologies, expanding its applications in fields such as bio-microarrays and microelectronics. In 2018, Zhou et al.^[56]used PET-RAFT polymerization to graft brush-like copolymer carboxybetaine methacrylate CBMA onto the surface of polyvinyl alcohol PVA hydrogel membranes, effectively enhancing the surface's biocompatibility and anti-adhesive properties. In 2019, Boyer's research group^[57]exploited the oxygen tolerance of PET-RAFT polymerization, using ZnTPP as a photocatalyst to graft binary polymer brushes onto silica surfaces, where specific areas of the surface could be polymer-functionalized by exposure to light, as shown in Figure 7a. By projecting optical images onto the functionalized substrate, optical microscopy images reproducing the polymer brushes were obtained, as shown in Figure 7b. In 2021, Hu et al.^[58]prepared drug-loaded hydrogels suitable for drug release by grafting N-isopropylacrylamide NIPAAm onto polyvinyl alcohol PVA hydrogels via organic dye-catalyzed PET-RAFT polymerization (as shown in Figure 7c). In 2022, Cao's research group^[59]carried out surface-initiated PET-RAFT polymerization (SI-PET-RAFT), separately polymerizing three fluorinated monomers—trifluoromethyl methacrylate TFEMA, hexafluorobutyl acrylate HFBMA, and dodecafluoroheptyl methacrylate DDFHMA—onto silicon wafers containing RAFT reagents to modify the surface with hydrophobic properties, investigating the relationship between surface contact angles and the type of fluorinated monomer, as shown in Figure 7d. In 2023, Potoski et al.^[60]successfully grafted monomers such as acrylic acid, methacrylic acid, and dimethylacrylamide onto the surface of poly-ε-caprolactone (PCL) nanofibers using PET-RAFT polymerization, preparing functional fiber mats with nanoscale dimensions and further advancing the development of nanofiber modification chemistry.

5.2 Biomedical Applications

PET-RAFT polymerization, with its flexibility and versatility, can be combined with various technologies. PISA, as an emerging technique for preparing drug delivery carriers, has extensive applications in the biomedical field. Currently, RAFT-controlled PISA (polymerization-induced self-assembly) technology has successfully produced block copolymer nanoparticles with diverse morphologies (spherical, worm-like, rod-shaped, vesicular, etc.), sizes (nano- and submicron-scale), and functional loadings. PISA refers to the process where the length of the hydrophobic segment of amphiphilic block copolymers continuously increases during polymerization, gradually reducing the solubility of the copolymer. When the hydrophobic segment reaches a certain length, the block copolymer undergoes self-assembly to form aggregates, and the morphology of these aggregates changes with variations in the ratio of hydrophilic to hydrophobic segments. By combining PET-RAFT technology with PISA self-assembly, assemblies with different morphologies, such as capsules, can be obtained, and these products hold potential application value in the field of controlled drug release. In 2015, Boyer's research group^[61]first applied PET-RAFT polymerization to PISA-induced self-assembly, successfully preparing spherical micelles, worm-like micelles, and vesicle-shaped aggregates. In the same year, Boyer's research group^[62]used PET-RAFT-PISA technology, employing o-nitrobenzyl methacrylate (NBMA) as the reactive monomer and zinc tetraphenylporphyrin (ZnTPP) and pheophorbide A (PheoA) as photocatalysts, to obtain spherical micellar nanoparticles that can be cleaved under UV light at room temperature and visible light (λ=560~655 nm). These products show promise for remote-controlled drug release. Since then, numerous reports on PET-RAFT technology and PISA have emerged. In 2022, Cao's research group^[59]conducted PET-RAFT-PISA using the macromolecular RAFT agent POEGMA-CDTPA and a series of fluorinated monomers under near-infrared light (740 nm), yielding uniformly sized nanoparticle assemblies that remain stable in various solvents, including DMSO, DMF, and dichloromethane. Also in the same year, Boyer's research group^[63]used tetrasulfonated zinc phthalocyanine (ZnPcS₄) as a photocatalyst to synthesize polymer nanoparticles with consistent morphology for the first time via thick-barrier synthesis under near-infrared (NIR) light and aqueous polymerization conditions. These products are expected to bring new opportunities for development in the biomedical field.

According to reports, when synthesizing three-dimensional polymer networks via PET-RAFT polymerization, its unique reaction mechanism allows for better control over polymer growth and backbone structure, resulting in more uniform polymer networks^[64]. Among 3D cross-linked materials, hydrogels are widely used in the biomedical field due to their high water content, cell compatibility, and tunable mechanical properties. In 2022, Yu et al.^[65] developed a multifunctional bilayer hydrogel for wound healing. Thanks to the oxygen tolerance and biocompatibility of PET-RAFT polymerization, the two hydrogel layers were covalently connected through PET-RAFT polymerization, as shown in Figure 8. In 2023, Arno et al.^[11] utilized the cell-compatible photocatalyst EY under visible light (450nm) to prepare highly cell-compatible and self-healing cell scaffolds via PET-RAFT polymerization in phosphate-buffered saline (PBS) and cell culture medium. Cells encapsulated within these scaffolds could survive for an extended period (7 days), as illustrated in Figure 9.

5.3 3D printing, laser writing

Applying PET-RAFT polymerization to 3D printing not only achieves spatiotemporal control over the 3D printing process but also enables further functionalization of the printed materials^[66-67]. In 2019, Boyer's research group^[68]applied PET-RAFT technology to the 3D printing process, using two photocatalysts—organic dyes Eosin Y (EY) and Erythrosine B (EB)—and tertiary amine as a co-catalyst, to obtain a non-toxic, metal-free, and environmentally friendly hydrogel material. By varying the photopolymerization time for each layer of the hydrogel, it was observed that after dehydration and subsequent re-swelling, the hydrogel material gradually deformed, as shown in Figure 10a.Additionally, dormant RAFT-terminated polymer chains could be re-initiated under green light irradiation in the presence of EB, and during the secondary photopolymerization of the 3D-printed material, strong fluorescence was only observed in the "UNSW" area exposed to light, as illustrated in Figure 10b.In 2022, Zhuang Luoxin et al. from Zhengzhou University^[69]employed PET-RAFT polymerization for the preparation of PDMS gels, resulting in PDMS gels containing thiocarbonyl compounds with a more uniform gel network. Even under aerobic conditions, these gels exhibited a rapid curing rate upon exposure to light, allowing for the simple and quick printing of high-precision PDMS lettering gels on a DLP 3D printer.

In addition, the mild reaction conditions and extremely short reaction time of PET-RAFT polymerization also create favorable conditions for laser writing. By utilizing direct laser writing (DLW) technology, precise micrometer-scale 3D structures can be generated on surfaces through digital control of the laser beam and multiphoton absorption processes, enabling high-precision surface functionalization. In 2021, Wu et al.^[70]first applied light-mediated RAFT polymerization to 3D laser writing, obtaining microstructures with feature sizes of approximately 500 nm. In 2023, Förster et al.^[71]used ZnTPP as a photocatalyst under 405 nm laser irradiation to directly initiate PET-RAFT polymerization within the nanoscale pores of mesoporous silica films, achieving millimeter-scale block copolymer patterns. The polymer molecular weight within the mesoporous membrane was regulated by adjusting laser power, irradiation time, and the addition of free RAFT reagents.

6 Conclusion and Outlook

PET-RAFT polymerization technology has achieved significant progress in the field of polymer synthesis due to its characteristics such as low energy consumption, mild reaction conditions, strong spatiotemporal controllability, and excellent oxygen resistance. However, as an emerging technology, PET-RAFT polymerization has also revealed certain shortcomings during its development, which urgently require further optimization and improvement. First, the photoinitiators widely used in PET-RAFT polymerization are predominantly metal-based catalysts (such as Ir and Ru complexes) or metal salt-containing catalysts. Although these catalysts exhibit extremely high catalytic efficiency, their residues may negatively impact polymer performance, for example by inducing material degradation, discoloration, or reduced mechanical properties. Moreover, metal residues are particularly detrimental in applications with stringent safety requirements, such as biomedical products and food packaging, and are inconsistent with the sustainable development goals of green chemistry. At the same time, the high cost of metal catalysts and their complex recycling processes also limit their potential for industrial-scale production. In contrast, certain metal-free organic photoinitiators (such as Rose Bengal Y) can avoid metal contamination; however, they are prone to photobleaching under prolonged light exposure, resulting in a significant decline in catalytic efficiency and affecting catalyst reusability and economic viability. Second, in terms of solvent selection, the applicability of PET-RAFT polymerization is relatively narrow. Particularly in aqueous systems, some catalysts may have their reaction performance limited due to solubility and stability issues. Therefore, it is crucial to develop catalysts that can adapt to various solvent environments and possess high stability. Despite these limitations, PET-RAFT polymerization still demonstrates broad application prospects. With continuous advancements in catalyst design and process optimization, novel photoinitiators have become capable of precisely controlling stereochimistry while regulating polymerization reactions. On one hand, the unique advantages of PET-RAFT polymerization in processing accuracy, on-demand manufacturing, and biocompatibility have driven its application in the large-scale fabrication of micron- and nanoscale three-dimensional structures, greatly promoting the industrial development of living radical polymerization. On the other hand, catalysts capable of absorbing long-wavelength visible light have significantly improved the environmental compatibility of PET-RAFT polymerization, opening up new avenues for the green synthesis of polymeric materials.

In the future, research on PET-RAFT polymerization technology will focus on developing highly efficient catalysts capable of absorbing visible and infrared light, thereby reducing side reactions and lowering economic costs. Meanwhile, the inherent safety of long-wavelength light sources opens up more possibilities for its application in the biomedical field. However, currently, the variety of available catalysts remains limited, with high prices and complex purification processes. Therefore, there is an urgent need to further develop low-cost, high-efficiency, non-toxic or low-toxicity catalysts, and to design catalytic systems with long-wavelength absorption characteristics, enhancing the utilization efficiency of low-energy photons, optimizing the compatibility between photopolymerization and the environment, and achieving truly green synthesis. Through these improvements, PET-RAFT polymerization technology is expected to make greater contributions to the functionalization, greening, and industrialization of polymeric materials.

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