Exploiting Wavelength Orthogonality for Successive Photoinduced

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Letter Cite This: ACS Macro Lett. 2018, 7, 1376−1382

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Exploiting Wavelength Orthogonality for Successive Photoinduced Polymerization-Induced Self-Assembly and Photo-Crosslinking Sihao Xu,† Jonathan Yeow,*,† and Cyrille Boyer*,† †

Centre for Advanced Macromolecular Design and Australian Centre for NanoMedicine, School of Chemical Engineering, The University of New South Wales, Sydney, NSW 2052, Australia

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S Supporting Information *

ABSTRACT: We report a facile benchtop process for the synthesis of cross-linked polymeric nanoparticles by exploiting wavelength-selective photochemistry to perform orthogonal photoinduced polymerization-induced self-assembly (Photo-PISA) and photo-crosslinking processes. We first established that the water-soluble photocatalyst, zinc meso-tetra(N-methyl-4-pyridyl) porphine tetrachloride (ZnTMPyP) could activate the aqueous PET-RAFT dispersion polymerization of hydroxypropyl methacrylate (HPMA). This photo-PISA process could be conducted under low energy red light (λmax = 595 nm, 10.2 mW/ cm2) and without deoxygenation due to the action of the singlet oxygen quencher, biotin (vitamin B7), which allowed for the synthesis of a range of nanoparticle morphologies (spheres, worms, and vesicles) directly in 96-well plates. To perform wavelength selective nanoparticle cross-linking, we added the photoresponsive monomer, 7-[4-(trifluoromethyl)coumarin] methacrylamide (TCMAm) as a comonomer without inhibiting the evolution of the nanoparticle morphology. Importantly, under red light, exclusive activation of the photo-PISA process occurs, with no evidence of TCMAm dimerization under these conditions. Subsequent switching to a UV source (λmax = 365 nm, 10.2 mW/cm2) resulted in rapid cross-linking of the polymer chains, allowing for retention of the nanoparticle morphology in organic solvents. This facile synthesis of cross-linked spheres, worms, and vesicles demonstrates the utility of orthogonal light-mediated chemistry for performing decoupled wavelength selective chemical processes.

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hinder morphological transitions and reduce colloidal stability.21 To address this issue, cross-linking can be decoupled from the polymerization process by employing postpolymerization cross-linking either by the addition of a monomeric cross-linker at the end of the PISA synthesis22,23 or by the incorporation of reactive monomers, followed by the postpolymerization addition of appropriate exogenous coupling reagents such as diamines.24−26 Alternatively, An’s group recently demonstrated that in situ cross-linking during PISA could be conducted in the presence of asymmetric cross-linkers without loss of morphological control, although the degree of cross-linking was limited to 90%) and relatively narrow molecular weight distributions (Đ < 1.3) were obtained (Figures 2A, SI and S3). Furthermore, 1378

DOI: 10.1021/acsmacrolett.8b00741 ACS Macro Lett. 2018, 7, 1376−1382

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ACS Macro Letters

Figure 3. (A) Experimental and characterization data for the PET-RAFT dispersion copolymerization of HPMA and TCMAm (20 mol %) with varying target DPs. Polymerizations were conducted in the presence of biotin in 96-well plates under red light irradiation (λmax = 595 nm, 10.2 mW/cm2) using a total solids content of 20 wt %. Corresponding TEM images of self-assembled polymeric nanoparticles acquired (B) in water and (C) after 3 h of UV irradiation (10.2 mW/cm2) and subsequent dilution with MeOH. Additional TEMs for PISA-11 and PISA-13 are provided in SI, Figure S17.

1.4; SI, Figure S7). This result demonstrates the selective activation of ZnTMPyP mediated PET-RAFT polymerization under red light since dimerization of the TCMAm side chains would be expected to cause significant branching, and hence, broadened molecular weight distributions. TEM imaging confirmed that as the DP of the hydrophobic block (PHPMA-co-PTCMAm) was increased, the nanoparticle morphology evolved from spheres (DP200, PISA-10) to worms (DP300, PISA-12) and finally vesicles (DP400, PISA14), in agreement with our previous results (Figure 3B). Notably, the addition of TCMAm at 20 mol% did not hinder the morphological evolution to higher order nanostructures which is in contrast to typical PISA behavior when a traditional cross-linking monomer such as ethylene glycol dimethacrylate is employed.21 Interestingly, the required DP of PHPMA-coPTCMAm to trigger morphological evolution was different to that obtained for the pure PHPMA block (Figure 2A,B), which was attributed to the effect of the hydrophobic TCMAm monomer on the packing parameter. According to NMR, the polymerization of TCMAm was relatively slow compared to HPMA, suggesting the formation of a gradient PHPMA-gradPTCMAm block due to the difference in reactivity ratios (SI, Figure S8A).60−62 Despite this effect, it is evident that the incorporation of TCMAm (in contrast with conventional cross-linkers) did not affect the level of polymerization control (SI, Figure S8B) or inhibit the evolution of the nanoparticle morphology from spheres to worms and vesicles. Importantly, in contrast with the in situ cross-linking approach developed by

cross-linking reactions (SI, Figure S4). To achieve this, we exploit the well-known [2 + 2] cycloaddition reaction of coumarin derivatives under UV light to cause cross-linking of the self-assembled polymer chains.59 We hypothesized that the coumarin based monomer, 7-[4-(trifluoromethyl)coumarin] methacrylamide (TCMAm) when added as a comonomer would exclusively undergo radical polymerization under low energy red light after which UV light could be used to induce dimerization due to its strong absorption peak centered at ∼340 nm (SI, Figure S4 and Scheme S1). The dimerization reaction was first studied by irradiation of a methanolic solution of TCMAm with UV light (λmax = 365 nm, 10.2 mW/ cm2; SI, Figure S5). NMR analysis revealed that after 5 h of UV irradiation, approximately 73% of the monomer had dimerized as indicated by the shift of the C-3 methine proton from 6.9 to 4.6 ppm. In contrast, irradiation of TCMAm with red light (λmax = 595 nm, 10.2 mW/cm2) for 17 h resulted in no dimerization, suggesting that cross-linking will not occur under the PET-RAFT dispersion polymerization conditions employed in this study (SI, Figure S6). We therefore attempted to copolymerize TCMAm (20 mol %) with HPMA in order to generate coumarin functional nanoparticles. To aid in solubilization of TCMAm under aqueous conditions, a small amount of DMF (5 v/v%) was added as a cosolvent. Under these conditions, high monomer conversions (α > 94%) were still achievable within 4 h of red light irradiation (λmax = 595 nm, 10.2 mW/cm2; Figure 3A) with good control over the molecular weight distribution (Đ < 1379

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ACS Macro Letters An and co-workers,28 this decoupled approach proceeds irrespective of the relative reactivities of each monomer and can tolerate higher incorporation of functional monomers (20 mol % vs 6 mol %). To test the ability of the coumarin moieties to cross-link the PEG113-b-(PHPMA-grad-PTCMAm) nanoparticles, we first diluted the dispersions to a concentration of ∼50 mg/mL to improve the penetration of UV light through the cloudy dispersion and minimize the occurrence of interparticle crosslinking. Since these polymerizations were conducted to near quantitative monomer conversion (>95%), no purification was applied. In a 96-well plate, the coumarin functional sphere, worm and vesicle nanoparticle dispersions (PISA-10, PISA-12, and PISA-14, respectively) were subjected to UV irradiation (λmax = 365 nm, 10.2 mW/cm2) for 3 h to trigger the [2 + 2] cycloaddition of the TCMAm side chains. Under these conditions, UV−vis spectroscopy revealed a decrease in the absorption of the TCMAm residues at ∼345 nm when aliquots of the dispersion were diluted in methanol (MeOH), indicating dimerization of the coumarin residues (see SI, for further discussion on the effects of UV light on the crosslinking, Figures S9 and S10). Importantly, under UV irradiation no macroscopic precipitation or gelation was observed. In contrast, at a total solids content of 20 wt %, gelation due to interparticle cross-linking occurred when the dispersion was exposed to extended periods of UV light irradiation which was attributed to the high density of coumarin moieties (Figure S11, left). To test the stability of these nanoparticles to organic solvents, we diluted our nanoparticles with MeOH, a good solvent for both hydrophilic and hydrophobic blocks, to a concentration of 0.1 mg/mL. DLS analysis of the non-UV irradiated nanoparticles acquired after dilution in MeOH revealed the degradation of the nanoparticle morphology to form unimeric polymers (or micelle-like aggregates) in the size range of ∼10 nm due to the solubilization of the polymer chains (SI, Figure S12). In comparison, the UV-irradiated PEG113-b-(PHPMA-grad-PTCMAm) nanoparticles were much more stable in MeOH, indicating successful cross-linking of the polymer chains. For all three cross-linked morphologies, DLS analysis indicated that the intensity average diameter was significantly larger in MeOH compared to water, which was attributed to the swelling of the cross-linked PEG113-b(PHPMA-grad-PTCMAm) chains in MeOH. To demonstrate the importance of TCMAm to the cross-linking process, we also subjected noncoumarin functionalized nanoparticles (PEG113-b-PHPMA) to the same UV irradiation conditions and observed little change in the molecular weight distribution indicating a lack of cross-linking in the absence of TCMAm (SI, Figure S13). TEM imaging of methanolic solutions of the UV irradiated PEG113-b-(PHPMA-grad-PTCMAm) nanoparticles was performed and, in each case, similar morphologies were observed before and after cross-linking (Figures 3C and S14). Finally, having demonstrated that photo-cross-linking can be performed under dilute conditions (∼50 mg/mL), we attempted to generate cross-linked PEG113-b-(PHPMA-gradPTCMAm) nanoparticles without the need for dilution of the crude polymerization mixture. To minimize the occurrence of interparticle cross-linking and macroscopic gelation, we synthesized a range of nanoparticle morphologies with lower incorporation of the TCMAm monomer (5 and 10 mol % relative to HPMA) while maintaining a total solids content of

20 wt % (SI, Figure S15). After polymerization under red light (λmax = 595 nm, 10.2 mW/cm2) for 4 h, the crude polymerization mixtures for PISA-17 and PISA-20 were immediately irradiated with UV light (λmax = 365 nm, 10.2 mW/cm2) for 3 h to induce cross-linking. Due to the reduced concentration of TCMAm residues, no macroscopic gelation was observed according to visual examination (SI, Figure S11, right) and DLS analysis (SI, Figure S16). Furthermore, TEM of the nanoparticles obtained in water and MeOH confirmed retention of the nanoparticle morphology (primarily vesicles) during the cross-linking process, demonstrating that orthogonal photo-cross-linking can be conducted in a one-pot approach (SI, Figure S16). Together, these data demonstrate that we can exploit the red light absorption of ZnTMPyP to first perform PET-RAFT dispersion polymerization of HPMA and TCMAm (without unwanted dimerization), followed by exposure to UV light to trigger cross-linking and stabilization of the nanoparticle morphology. In conclusion, we have demonstrated a mild and robust platform exploiting PET-RAFT polymerization to synthesize polymeric nanoparticles of different morphologies. This process can be performed under low energy red light and has excellent tolerance to oxygen, allowing for nanoparticle synthesis to be conducted on a benchtop and in 96-well plates without deoxygenation. We have exploited the wavelength orthogonality of the [2 + 2] coumarin cycloaddition reaction and ZnTMPyP mediated PET-RAFT process to incorporate coumarin moieties during the red light mediated photo-PISA process without unwanted dimerization occurring. Subsequent activation of the coumarin dimerization reaction under high energy UV light enables cross-linking of the polymeric chains and stabilization of the nanoparticle morphology. To the best of our knowledge, this is the first time that orthogonal lightmediated chemistry has been applied to the PISA process opening up new avenues of research for exploiting wavelength selective chemical reactions in polymer self-assembly.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsmacrolett.8b00741. Additional experimental and characterization data (Figures S1−S17 and Scheme S1; PDF).

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Cyrille Boyer: 0000-0002-4564-4702 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS C.B. acknowledges the Australian Research Council (ARC) for his Future Fellowship (FT120100096). REFERENCES

(1) Chen, M.; Zhong, M.; Johnson, J. A. Light-Controlled Radical Polymerization: Mechanisms, Methods, and Applications. Chem. Rev. 2016, 116 (17), 10167−10211.

1380

DOI: 10.1021/acsmacrolett.8b00741 ACS Macro Lett. 2018, 7, 1376−1382

Letter

ACS Macro Letters (2) Corrigan, N.; Yeow, J.; Judzewitsch, P.; Xu, J.; Boyer, C. Seeing the Light: Advancing Materials Chemistry through Photopolymerization. Angew. Chem., Int. Ed. 2018, DOI: 10.1002/anie.201805473. (3) Theriot, J. C.; McCarthy, B. G.; Lim, C.-H.; Miyake, G. M. Organocatalyzed Atom Transfer Radical Polymerization: Perspectives on Catalyst Design and Performance. Macromol. Rapid Commun. 2017, 38 (13), 1700040. (4) Leibfarth, F. A.; Mattson, K. M.; Fors, B. P.; Collins, H. A.; Hawker, C. J. External Regulation of Controlled Polymerizations. Angew. Chem., Int. Ed. 2013, 52 (1), 199−210. (5) Goldmann, A. S.; Glassner, M.; Inglis, A. J.; Barner-Kowollik, C. Post-Functionalization of Polymers via Orthogonal Ligation Chemistry. Macromol. Rapid Commun. 2013, 34 (10), 810−849. (6) Canning, S. L.; Smith, G. N.; Armes, S. P. A Critical Appraisal of RAFT-Mediated Polymerization-Induced Self-Assembly. Macromolecules 2016, 49 (6), 1985−2001. (7) Wang, X.; An, Z. New Insights into RAFT Dispersion Polymerization-Induced Self-Assembly: From Monomer Library, Morphological Control, and Stability to Driving Forces. Macromol. Rapid Commun. 2018, 1800325. (8) Blanazs, A.; Armes, S. P.; Ryan, A. J. Self-Assembled Block Copolymer Aggregates: From Micelles to Vesicles and their Biological Applications. Macromol. Rapid Commun. 2009, 30 (4−5), 267−77. (9) Warren, N. J.; Armes, S. P. Polymerization-Induced SelfAssembly of Block Copolymer Nano-objects via RAFT Aqueous Dispersion Polymerization. J. Am. Chem. Soc. 2014, 136 (29), 10174− 10185. (10) Yeow, J.; Boyer, C. Photoinitiated Polymerization-Induced SelfAssembly (Photo-PISA): New Insights and Opportunities. Adv. Sci. 2017, 4 (7), 1700137. (11) Zhang, W.-J.; Hong, C.-Y.; Pan, C.-Y. Polymerization-Induced Self-Assembly of Functionalized Block Copolymer Nanoparticles and Their Application in Drug Delivery. Macromol. Rapid Commun. 2018, 1800279. (12) Cheng, G.; Pérez-Mercader, J. Polymerization-Induced SelfAssembly for Artificial Biology: Opportunities and Challenges. Macromol. Rapid Commun. 2018, 1800513. (13) Tan, J.; Liu, D.; Bai, Y.; Huang, C.; Li, X.; He, J.; Xu, Q.; Zhang, L. Enzyme-Assisted Photoinitiated Polymerization-Induced Self-Assembly: An Oxygen-Tolerant Method for Preparing Block Copolymer Nano-Objects in Open Vessels and Multiwell Plates. Macromolecules 2017, 50 (15), 5798−5806. (14) Yeow, J.; Shanmugam, S.; Corrigan, N.; Kuchel, R. P.; Xu, J.; Boyer, C. A Polymerization-Induced Self-Assembly Approach to Nanoparticles Loaded with Singlet Oxygen Generators. Macromolecules 2016, 49 (19), 7277−7285. (15) Tan, J.; Li, X.; Zeng, R.; Liu, D.; Xu, Q.; He, J.; Zhang, Y.; Dai, X.; Yu, L.; Zeng, Z.; Zhang, L. Expanding the Scope of Polymerization-Induced Self-Assembly: Z-RAFT-Mediated Photoinitiated Dispersion Polymerization. ACS Macro Lett. 2018, 7 (2), 255−262. (16) Ma, C.; Liu, X.; Wu, G.; Zhou, P.; Zhou, Y.; Wang, L.; Huang, X. Efficient Way to Generate Protein-Based Nanoparticles by in-Situ Photoinitiated Polymerization-Induced Self-Assembly. ACS Macro Lett. 2017, 6 (7), 689−694. (17) Blackman, L. D.; Varlas, S.; Arno, M. C.; Fayter, A.; Gibson, M. I.; O’Reilly, R. K. Permeable Protein-Loaded Polymersome Cascade Nanoreactors by Polymerization-Induced Self-Assembly. ACS Macro Lett. 2017, 6 (11), 1263−1267. (18) Blackman, L. D.; Varlas, S.; Arno, M. C.; Houston, Z. H.; Fletcher, N. L.; Thurecht, K. J.; Hasan, M.; Gibson, M. I.; O’Reilly, R. K. Confinement of Therapeutic Enzymes in Selectively Permeable Polymer Vesicles by Polymerization-Induced Self-Assembly (PISA) Reduces Antibody Binding and Proteolytic Susceptibility. ACS Cent. Sci. 2018, 4 (6), 718−723. (19) Tan, J.; Huang, C.; Liu, D.; Zhang, X.; Bai, Y.; Zhang, L. Alcoholic Photoinitiated Polymerization-Induced Self-Assembly (Photo-PISA): A Fast Route toward Poly(isobornyl acrylate)-Based Diblock Copolymer Nano-Objects. ACS Macro Lett. 2016, 5 (8), 894−899.

(20) Varlas, S.; Blackman, L. D.; Findlay, H. E.; Reading, E.; Booth, P. J.; Gibson, M. I.; O’Reilly, R. K. Photoinitiated PolymerizationInduced Self-Assembly in the Presence of Surfactants Enables Membrane Protein Incorporation into Vesicles. Macromolecules 2018, 51 (16), 6190−6201. (21) Sugihara, S.; Armes, S. P.; Blanazs, A.; Lewis, A. L. NonSpherical Morphologies from Cross-Linked Biomimetic Diblock Copolymers using RAFT Aqueous Dispersion Polymerization. Soft Matter 2011, 7 (22), 10787−10793. (22) Chambon, P.; Blanazs, A.; Battaglia, G.; Armes, S. P. Facile Synthesis of Methacrylic ABC Triblock Copolymer Vesicles by RAFT Aqueous Dispersion Polymerization. Macromolecules 2012, 45 (12), 5081−5090. (23) Figg, C. A.; Simula, A.; Gebre, K. A.; Tucker, B. S.; Haddleton, D. M.; Sumerlin, B. S. Polymerization-Induced Thermal SelfAssembly (PITSA). Chem. Sci. 2015, 6 (2), 1230−1236. (24) Chambon, P.; Blanazs, A.; Battaglia, G.; Armes, S. P. How Does Cross-Linking Affect the Stability of Block Copolymer Vesicles in the Presence of Surfactant? Langmuir 2012, 28 (2), 1196−1205. (25) Zhou, W.; Qu, Q.; Yu, W.; An, Z. Single Monomer for Multiple Tasks: Polymerization Induced Self-Assembly, Functionalization and Cross-Linking, and Nanoparticle Loading. ACS Macro Lett. 2014, 3 (12), 1220−1224. (26) Li, X.; Tan, J.; Xu, Q.; He, J.; Zhang, L. Photoinitiated Seeded RAFT Dispersion Polymerization: A Facile Method for the Preparation of Epoxy-Functionalized Triblock Copolymer NanoObjects. Macromol. Rapid Commun. 2018, 1800473. (27) Qu, Q.; Liu, G.; Lv, X.; Zhang, B.; An, Z. In Situ Cross-Linking of Vesicles in Polymerization-Induced Self-Assembly. ACS Macro Lett. 2016, 5 (3), 316−320. (28) Zhang, B.; Lv, X.; Zhu, A.; Zheng, J.; Yang, Y.; An, Z. Morphological Stabilization of Block Copolymer Worms Using Asymmetric Cross-Linkers during Polymerization-Induced SelfAssembly. Macromolecules 2018, 51 (8), 2776−2784. (29) Kottisch, V.; Michaudel, Q.; Fors, B. P. Photocontrolled Interconversion of Cationic and Radical Polymerizations. J. Am. Chem. Soc. 2017, 139 (31), 10665−10668. (30) Ohtsuki, A.; Lei, L.; Tanishima, M.; Goto, A.; Kaji, H. Photocontrolled Organocatalyzed Living Radical Polymerization Feasible over a Wide Range of Wavelengths. J. Am. Chem. Soc. 2015, 137 (16), 5610−5617. (31) Xu, J.; Shanmugam, S.; Fu, C.; Aguey-Zinsou, K.-F.; Boyer, C. Selective Photoactivation: From a Single Unit Monomer Insertion Reaction to Controlled Polymer Architectures. J. Am. Chem. Soc. 2016, 138 (9), 3094−3106. (32) Fu, C.; Xu, J.; Boyer, C. Photoacid-Mediated Ring Opening Polymerization Driven by Visible Light. Chem. Commun. 2016, 52 (44), 7126−7129. (33) Zhang, X.; Xi, W.; Huang, S.; Long, K.; Bowman, C. N. Wavelength-Selective Sequential Polymer Network Formation Controlled with a Two-Color Responsive Initiation System. Macromolecules 2017, 50 (15), 5652−5660. (34) Shah, P. K.; Stansbury, J. W.; Bowman, C. N. Application of an Addition−Fragmentation-Chain Transfer Monomer in Di(meth)acrylate Network Formation to reduce Polymerization Shrinkage Stress. Polym. Chem. 2017, 8 (30), 4339−4351. (35) Xi, W.; Peng, H.; Aguirre-Soto, A.; Kloxin, C. J.; Stansbury, J. W.; Bowman, C. N. Spatial and Temporal Control of Thiol-Michael Addition via Photocaged Superbase in Photopatterning and TwoStage Polymer Networks Formation. Macromolecules 2014, 47 (18), 6159−6165. (36) Xiong, X.; Xue, L.; Cui, J. Phototriggered Growth and Detachment of Polymer Brushes with Wavelength Selectivity. ACS Macro Lett. 2018, 7 (2), 239−243. (37) Gumbley, P.; Koylu, D.; Pawle, R. H.; Umezuruike, B.; Spedden, E.; Staii, C.; Thomas, S. W. Wavelength-Selective Disruption and Triggered Release with Photolabile Polyelectrolyte Multilayers. Chem. Mater. 2014, 26 (3), 1450−1456. 1381

DOI: 10.1021/acsmacrolett.8b00741 ACS Macro Lett. 2018, 7, 1376−1382

Letter

ACS Macro Letters (38) Hu, X.; Qureishi, Z.; Thomas, S. W. Light-Controlled Selective Disruption, Multilevel Patterning, and Sequential Release with Polyelectrolyte Multilayer Films Incorporating Four Photocleavable Chromophores. Chem. Mater. 2017, 29 (7), 2951−2960. (39) Ye, Q.; Huo, M.; Zeng, M.; Liu, L.; Peng, L.; Wang, X.; Yuan, J. Photoinduced Reversible Worm-to-Vesicle Transformation of AzoContaining Block Copolymer Assemblies Prepared by Polymerization-Induced Self-Assembly. Macromolecules 2018, 51 (9), 3308− 3314. (40) García-Fernández, L.; Herbivo, C.; Arranz, V. S. M.; Warther, D.; Donato, L.; Specht, A.; del Campo, A. Dual Photosensitive Polymers with Wavelength-Selective Photoresponse. Adv. Mater. 2014, 26 (29), 5012−5017. (41) Schenzel, A. M.; Moszner, N.; Barner-Kowollik, C. Disulfone Cross-Linkers for λ-Orthogonal Photoinduced Curing and Degradation of Polymeric Networks. ACS Macro Lett. 2017, 6 (1), 16−20. (42) Zhu, K.; Liu, G.; Zhang, G.; Hu, J.; Liu, S. Engineering CrossLinkable Plasmonic Vesicles for Synergistic Chemo-Photothermal Therapy Using Orthogonal Light Irradiation. Macromolecules 2018, DOI: 10.1021/acs.macromol.8b01653. (43) Zhang, W.-J.; Hong, C.-Y.; Pan, C.-Y. Efficient Fabrication of Photosensitive Polymeric Nano-objects via an Ingenious Formulation of RAFT Dispersion Polymerization and Their Application for Drug Delivery. Biomacromolecules 2017, 18 (4), 1210−1217. (44) Xu, J.; Jung, K.; Atme, A.; Shanmugam, S.; Boyer, C. A Robust and Versatile Photoinduced Living Polymerization of Conjugated and Unconjugated Monomers and Its Oxygen Tolerance. J. Am. Chem. Soc. 2014, 136 (14), 5508−5519. (45) Corrigan, N.; Rosli, D.; Jones, J. W. J.; Xu, J.; Boyer, C. Oxygen Tolerance in Living Radical Polymerization: Investigation of Mechanism and Implementation in Continuous Flow Polymerization. Macromolecules 2016, 49 (18), 6779−6789. (46) Ng, G.; Yeow, J.; Xu, J.; Boyer, C. Application of Oxygen Tolerant PET-RAFT to Polymerization-Induced Self-Assembly. Polym. Chem. 2017, 8, 2841−2851. (47) Yeow, J.; Chapman, R.; Xu, J.; Boyer, C. Oxygen Tolerant Photopolymerization for Ultralow Volumes. Polym. Chem. 2017, 8, 5012−5022. (48) Gormley, A. J.; Yeow, J.; Ng, G.; Conway, Ó .; Boyer, C.; Chapman, R. An Oxygen-Tolerant PET-RAFT Polymerization for Screening Structure−Activity Relationships. Angew. Chem., Int. Ed. 2018, 57 (6), 1557−1562. (49) Yeow, J.; Joshi, S.; Chapman, R.; Boyer, C. A Self-Reporting Photocatalyst for Online Fluorescence Monitoring of High Throughput RAFT Polymerization. Angew. Chem., Int. Ed. 2018, 57 (32), 10102−10106. (50) Ng, G.; Yeow, J.; Chapman, R.; Isahak, N.; Wolvetang, E.; Cooper-White, J. J.; Boyer, C. Pushing the Limits of High Throughput PET-RAFT Polymerization. Macromolecules 2018, 51 (19), 7600−7607. (51) Yeow, J.; Chapman, R.; Gormley, A. J.; Boyer, C. Up in the Air: Oxygen Tolerance in Controlled/Living Radical Polymerisation. Chem. Soc. Rev. 2018, 47 (12), 4357−4387. (52) Haack, R. A.; Swift, K. M.; Ruan, Q.; Himmelsbach, R. J.; Tetin, S. Y. The Photostability of the Commonly used Biotin-4-fluorescein Probe. Anal. Biochem. 2017, 531, 78−82. (53) Peddinti, B. S. T.; Scholle, F.; Ghiladi, R. A.; Spontak, R. J. Photodynamic Polymers as Comprehensive Anti-Infective Materials: Staying Ahead of a Growing Global Threat. ACS Appl. Mater. Interfaces 2018, 10 (31), 25955−25959. (54) Blanazs, A.; Madsen, J.; Battaglia, G.; Ryan, A. J.; Armes, S. P. Mechanistic Insights for Block Copolymer Morphologies: How Do Worms Form Vesicles? J. Am. Chem. Soc. 2011, 133 (41), 16581− 16587. (55) Destarac, M. On the Critical Role of RAFT Agent Design in Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization. Polym. Rev. 2011, 51 (2), 163−187. (56) Yeow, J.; Xu, J.; Boyer, C. Polymerization-Induced SelfAssembly Using Visible Light Mediated Photoinduced Electron

Transfer−Reversible Addition−Fragmentation Chain Transfer Polymerization. ACS Macro Lett. 2015, 4 (9), 984−990. (57) Tan, J.; Sun, H.; Yu, M.; Sumerlin, B. S.; Zhang, L. Photo-PISA: Shedding Light on Polymerization-Induced Self-Assembly. ACS Macro Lett. 2015, 4 (11), 1249−1253. (58) Blackman, L. D.; Doncom, K. E. B.; Gibson, M. I.; O’Reilly, R. K. Comparison of Photo- and Thermally Initiated PolymerizationInduced Self-Assembly: A Lack of End Group Fidelity Drives the Formation of Higher Order Morphologies. Polym. Chem. 2017, 8 (18), 2860−2871. (59) Kabb, C. P.; O’Bryan, C. S.; Deng, C. C.; Angelini, T. E.; Sumerlin, B. S. Photoreversible Covalent Hydrogels for Soft-Matter Additive Manufacturing. ACS Appl. Mater. Interfaces 2018, 10 (19), 16793−16801. (60) Kucharski, M.; Lubczak, R. Copolymerization of Hydroxyalkyl Methacrylates with Acrylamide and Methacrylamide I. Determination of Reactivity Ratios. J. Appl. Polym. Sci. 1997, 64 (7), 1259−1265. (61) Jayasimha Reddy, G.; Venkata Naidu, S.; Rami Reddy, A. V. Synthesis and Characterization of Poly(N-phenyl ethacrylamide-comethyl methacrylate) and Reactivity Ratios Determination. J. Appl. Polym. Sci. 2003, 90 (8), 2179−2186. (62) Soykan, C.; Delibas, A.; Coskun, R. Copolymers of N-(4bromophenyl)-2-methacrylamide with 2-Hydroxyethyl Methacrylate. eXPRESS Polym. Lett. 2007, 1, 594−603.

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