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].

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.

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.

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.

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.

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.

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.