Polymer-based phototherapeutic nanoagents provide an effective route to integrate fluorescence (FL) and photoacoustic (PA) imaging with photothermal therapy (PTT) and photodynamic therapy (PDT). This review highlights covalently engineered polymer-chromophore systems, in which photothermal agents or photosensitizers are incorporated into polymer backbones via robust linkages (e.g., amide/ester and related bonds) or through polymerizable chromophore monomers. Tumor microenvironment-responsive motifs (e.g., disulfide and thioketal units) further enable activatable behavior and improved selectivity. Importantly, amphiphilic conjugates self-assemble into nanodots, polymersomes, and nanofibers, and assembly morphology and chromophore packing can reprogram excited-state pathways, thereby tuning FL/PA outputs, photothermal conversion, and Type I/II ROS generation. We discuss representative porphyrin/phthalocyanine, heptamethine cyanine, Changsha Red (xanthene-derived), and Nile Blue platforms for multimodal image-guided cancer phototherapy, including mechanism-integrated strategies, such as microenvironment activation, organelle targeting, and immunomodulation. Finally, we outline key challenges and opportunities for translation, including quantitative structure-property correlations, scalable morphology control, standardized photophysical reporting, and biosafety evaluation.
| [1] |
Bray F, Laversanne M, Sung H, Ferlay J, Siegel R L, Soerjomataram I, Jemal A. CA: Cancer J. Clin.. 2024, 74229
|
| [2] |
Li M, Xiong J, Zhang Y, Yu L, Yue L, Yoon C, Kim Y, Zhou Y, Chen X, Xu Y, Peng X, Kim J S. Chem. Soc. Rev.. 2025, 547025.
|
| [3] |
Zhou X-Q, Wang P, Ramu V, Zhang L, Jiang S, Li X, Abyar S, Papadopoulou P, Shao Y, Bretin L, Siegler MA, Buda F, Kros A, Fan J, Peng X, Sun W, Bonnet S. Nat. Chem.. 2023, 15980.
|
| [4] |
Idris N M, Gnanasammandhan M K, Zhang J, Ho P C, Mahendran R, Zhang Y. Nat. Med.. 2012, 181580.
|
| [5] |
Wang Z, Zhan M, Hu X. Chem. Eur. J.. 2022, 28e202200042.
|
| [6] |
Niu L-Y, Chen Y-Z, Zheng H-R, Wu L-Z, Tung C-H, Yang Q-Z. Chem. Soc. Rev.. 2015, 446143.
|
| [7] |
Lin Y, Niu L-Y, Teng K-X, Yang Q-Z. J. Am. Chem. Soc.. 2025, 14735172.
|
| [8] |
Park J, Choi S, Knieling F, Clingman B, Bohndiek S, Wang L V, Kim C. Nat. Rev. Bioeng.. 2025, 3193.
|
| [9] |
Liu J, Cheng P, Xu C, Pu K. Nat. Biomed. Eng.. 2025, 9618.
|
| [10] |
Wang Z, Zhan M, Li W, Chu C, Xing D, Lu S, Hu X. Angew. Chem. Int. Ed.. 2021, 604720.
|
| [11] |
Han H, Ma X, Deng W, Zhang J, Tang S, Pak O S, Zhu L, Criado-Hidalgo E, Gong C, Karshalev E, Yoo J, You M, Liu A, Wang C, Shen H K, Patel P N, Hays C L, Gunnarson P J, Li L, Zhang Y, Dabiri J O, Wang L V, Shapiro M G, Wu D, Zhou Q, Greer J R, Gao W. Sci. Robot.. 2024, 9eadp3593.
|
| [12] |
Yang K, Zhao S, Li B, Wang B, Lan M, Song X. Coord. Chem. Rev.. 2022, 454214330.
|
| [13] |
Jung H S, Verwilst P, Sharma A, Shin J, Sessler J L, Kim J S. Chem. Soc. Rev.. 2018, 472280.
|
| [14] |
Overchuk M, Weersink R A, Wilson B C, Zheng G. ACS Nano. 2023, 177979.
|
| [15] |
Zheng B-D, He Q-X, Li X, Yoon J, Huang J-D. Coord. Chem. Rev.. 2021, 426213548.
|
| [16] |
Sharma A, Verwilst P, Li M, Ma D, Singh N, Yoo J, Kim Y, Yang Y, Zhu J-H, Huang H, Hu X-L, He X-P, Zeng L, James T D, Peng X, Sessler J L, Kim J S. Chem. Rev.. 2024, 1242699.
|
| [17] |
Alander J T, Kaartinen I, Laakso A, Pätilä T, Spillmann T, Tuchin V V, Venermo M, Välisuo P. Int. J. Biomed. Imaging. 2012, 2012940585.
|
| [18] |
Wu F, Zheng B, Qiu X, Hu T, Yang Y, Yang K, Zhou B, Ma Q, Pang D-W, Xiong H. Angew. Chem. Int. Ed.. 2025, 64e202423059.
|
| [19] |
Li D-H, Gamage R S, Oliver A G, Patel N L, Muhammad Usama S, Kalen J D, Schnermann M J, Smith B D. Angew. Chem. Int. Ed.. 2023, 62e202305062.
|
| [20] |
Sun W, Guo S, Hu C, Fan J, Peng X. Chem. Rev.. 2016, 1167768.
|
| [21] |
Jiang G, Liu H, Liu H, Ke G, Ren T-B, Xiong B, Zhang X-B, Yuan L. Angew. Chem. Int. Ed.. 2024, 63e202315217.
|
| [22] |
Kingsbury C J, Senge M O. Coord. Chem. Rev.. 2021, 431213760.
|
| [23] |
Auwärter W, Écija D, Klappenberger F, Barth J V. Nat. Chem.. 2015, 7105.
|
| [24] |
Yuan L, Lin W, Yang Y, Chen H. J. Am. Chem. Soc.. 2012, 1341200.
|
| [25] |
Yuan L, Lin W, Zheng K, He L, Huang W. Chem. Soc. Rev.. 2013, 42622.
|
| [26] |
Wang C, Zhao W, Cao B, Wang Z, Zhou Q, Lu S, Lu L, Zhan M, Hu X. Chem. Mater.. 2020, 327725.
|
| [27] |
Zhao J, Ren L-Q, Lan D, Zhan B, Zhang J, Mu J, He C. Nat. Commun.. 2025, 169719.
|
| [28] |
Loudet A, Burgess K. Chem. Rev.. 2007, 1074891.
|
| [29] |
Yao C, Chen Y, Zhao M, Wang S, Wu B, Yang Y, Yin D, Yu P, Zhang H, Zhang F. Angew. Chem. Int. Ed.. 2022, 61e202114273.
|
| [30] |
Li M, Xia J, Tian R, Wang J, Fan J, Du J, Long S, Song X, Foley J W, Peng X. J. Am. Chem. Soc.. 2018, 14014851.
|
| [31] |
Li M, Shao Y, Kim J H, Pu Z, Zhao X, Huang H, Xiong T, Kang Y, Li G, Shao K, Fan J, Foley J W, Kim J S, Peng X. J. Am. Chem. Soc.. 2020, 1425380.
|
| [32] |
Li M, Xiong T, Du J, Tian R, Xiao M, Guo L, Long S, Fan J, Sun W, Shao K, Song X, Foley J W, Peng X. J. Am. Chem. Soc.. 2019, 1412695.
|
| [33] |
Shen Z, Zheng S, Fang Y, Zhang G, Zhu C, Liu S, Hu J. Angew. Chem. Int. Ed.. 2023, 62e202219153.
|
| [34] |
Yuan L, Lin W, Zhao S, Gao W, Chen B, He L, Zhu S. J. Am. Chem. Soc.. 2012, 13413510.
|
| [35] |
Yin J, Huang L, Wu L, Li J, James T D, Lin W. Chem. Soc. Rev.. 2021, 5012098.
|
| [36] |
Hao Q, Wang Z, Zhao W, Wen L, Wang W, Lu S, Xing D, Zhan M, Hu X. ACS Appl. Mater. Interfaces. 2020, 1249489.
|
| [37] |
Li X, Lovell JF, Yoon J, Chen X. Nat. Rev. Clin. Oncol.. 2020, 17657.
|
| [38] |
Zhou Z, Song J, Nie L, Chen X. Chem. Soc. Rev.. 2016, 456597.
|
| [39] |
Wang Z, Jin A, Yang Z, Huang W. ACS Nano. 2023, 178935.
|
| [40] |
Hong G, Antaris A L, Dai H. Nat. Biomed. Eng.. 2017, 10010.
|
| [41] |
Du F, Chen R, Feng E, Dai H, Yu F. Coord. Chem. Rev.. 2026, 551217460.
|
| [42] |
Yuan W Z, Lu P, Chen S, Lam J W Y, Wang Z, Liu Y, Kwok HS, Ma Y, Tang B Z. Adv. Mater.. 2010, 222159.
|
| [43] |
Wang C, Zhang T, Lin W. Chem. Rev.. 2012, 1121084.
|
| [44] |
Ge Z, Liu S. Chem. Soc. Rev.. 2013, 427289.
|
| [45] |
Hu J, Zhang G, Liu S. Chem. Soc. Rev.. 2012, 415933.
|
| [46] |
Song R, Tan J, Cen J, Li Z, Zhang Y, Hou M, Li R, Tang L, Hu J, Liu S. J. Am. Chem. Soc.. 2025, 1472889.
|
| [47] |
Li K, Liu B. Chem. Soc. Rev.. 2014, 436570.
|
| [48] |
Chu B, Liu B. Natl. Sci. Rev.. 2025, 121.
|
| [49] |
Kim J, Lee Y, Kim Y, Rha H, Kim D, Debnath S, Pu K, Kang H, Kim J S. Chem. Rev.. 2025, 1259012.
|
| [50] |
Xu C, Zhang Y, Liang G, Pu K. Nat. Mater.. 2025, 241694.
|
| [51] |
Shi Y, Yu Q, Tan L, Wang Q, Zhu W-H. Angew. Chem. Int. Ed.. 2025, 64e202503776.
|
| [52] |
Li H, Huang M, Wei Z, He J, Ma Y, Lu C, Jin A, Wang Z, Wen L. Front. Bioeng. Biotechnol.. 2022, 101032571.
|
| [53] |
Burda C, Chen X, Narayanan R, El-Sayed M A. Chem. Rev.. 2005, 1051025.
|
| [54] |
Fu H-B, Yao J-N. J. Am. Chem. Soc.. 2001, 1231434.
|
| [55] |
Ng K K, Zheng G. Chem. Rev.. 2015, 11511012.
|
| [56] |
Petkau K, Kaeser A, Fischer I, Brunsveld L, Schenning A P H J. J. Am. Chem. Soc.. 2011, 13317063.
|
| [57] |
O’Connor A E, Gallagher W M, Byrne A T. Photochem. Photobiol.. 2009, 851053.
|
| [58] |
Tanaka T, Osuka A. Chem. Soc. Rev.. 2015, 44943.
|
| [59] |
Lin Z, Zhang Z-M, Chen Y-S, Lin W. Angew. Chem. Int. Ed.. 2016, 5513739.
|
| [60] |
Song W, Kuang J, Li C-X, Zhang M, Zheng D, Zeng X, Liu C, Zhang X-Z. ACS Nano. 2018, 121978.
|
| [61] |
Han K, Lei Q, Wang S-B, Hu J-J, Qiu W-X, Zhu J-Y, Yin W-N, Luo X, Zhang X-Z. Adv. Funct. Mater.. 2015, 252961.
|
| [62] |
Zhang S, Yang N, Sun S, Zhao H, Wang W, Nie J, Pei Z, He W, Zhang L, Cheng L, Cheng Z. Acta Biomater.. 2025, 193406.
|
| [63] |
Liu Y, Wang H, Li S, Chen C, Xu L, Huang P, Liu F, Su Y, Qi M, Yu C, Zhou Y. Nat. Commun.. 2020, 111724.
|
| [64] |
Li W, Zheng C, Pan Z, Chen C, Hu D, Gao G, Kang S, Cui H, Gong P, Cai L. Biomaterials. 2016, 10110.
|
| [65] |
Park K, Ahn J W, Kim J H, Kim J W. Int. J. Biol. Macromol.. 2022, 218384.
|
| [66] |
Kim J, Park W, Kim D, Lee E S, Lee D H, Jeong S, Park J M, Na K. Adv. Funct. Mater.. 2019, 291900084.
|
| [67] |
Liu X, Zhan W, Gao G, Jiang Q, Zhang X, Zhang H, Sun X, Han W, Wu F-G, Liang G. J. Am. Chem. Soc.. 2023, 1457918.
|
| [68] |
Zou Q, Abbas M, Zhao L, Li S, Shen G, Yan X. J. Am. Chem. Soc.. 2017, 1391921.
|
| [69] |
Sun B, Chang R, Cao S, Yuan C, Zhao L, Yang H, Li J, Yan X, van Hest J C M. Angew. Chem. Int. Ed.. 2020, 5920582.
|
| [70] |
Lovell J F, Jin C S, Huynh E, Jin H, Kim C, Rubinstein J L, Chan W C W, Cao W, Wang L V, Zheng G. Nat. Mater.. 2011, 10324.
|
| [71] |
Boni L, David G, Mangano A, Dionigi G, Rausei S, Spampatti S, Cassinotti E, Fingerhut A. Surg. Endosc.. 2015, 292046.
|
| [72] |
Cassinotti E, Al-Taher M, Antoniou S A, Arezzo A, Baldari L, Boni L, Bonino M A, Bouvy N D, Brodie R, Carus T, Chand M, Diana M, Eussen M M M, Francis N, Guida A, Gontero P, Haney C M, Jansen M, Mintz Y, Morales-Conde S, Muller-Stich B P, Nakajima K, Nickel F, Oderda M, Parise P, Rosati R, Schijven M P, Silecchia G, Soares A S, Urakawa S, Vettoretto N. Surg. Endosc.. 2023, 371629.
|
| [73] |
Chen Q-Y, Zhong Q, Liu Z-Y, Li P, Lin G-T, Zheng Q-L, Wang J-B, Lin J-X, Lu J, Cao L-L, Lin M, Tu R-H, Huang Z-N, Zeng G-R, Jiang M-C, Wang H-G, Huang X-B, Xu K-X, Li Y-F, Zheng C-H, Xie J-W, Huang C-M. Nat. Commun.. 2023, 147413.
|
| [74] |
Abels C, Karrer S, Bäumler W, Goetz A E, Landthaler M, Szeimies R M. Br. J. Cancer. 1998, 771021.
|
| [75] |
Quan Y H, Oh C H, Jung D, Lim J-Y, Choi B H, Rho J, Choi Y, Han K N, Kim B-M, Kim C, Park J-H, Kim H K. JAMA Surg.. 2020, 155732.
|
| [76] |
Lim C, Vibert E, Azoulay D, Salloum C, Ishizawa T, Yoshioka R, Mise Y, Sakamoto Y, Aoki T, Sugawara Y, Hasegawa K, Kokudo N. J. Visc. Surg.. 2014, 151117.
|
| [77] |
Yang L, Hou X, Zhang Y, Wang D, Liu J, Huang F, Liu J. J. Control. Release. 2021, 339114.
|
| [78] |
Yang L, Zhang C, Liu J, Huang F, Zhang Y, Liang X-J, Liu J. Adv. Healthc. Mater.. 2020, 91901616.
|
| [79] |
Yu H, Cui Z, Yu P, Guo C, Feng B, Jiang T, Wang S, Yin Q, Zhong D, Yang X, Zhang Z, Li Y. Adv. Funct. Mater.. 2015, 252489.
|
| [80] |
Han Y, Li J, Zan M, Luo S, Ge Z, Liu S. Polym. Chem.. 2014, 53707.
|
| [81] |
Chen M, Li R, Liu Y, Song X, Tian J, Fu Y, Yang Y, Liu C, Zhang Q. Chem. Eng. J.. 2021, 406126745.
|
| [82] |
Yuan J, Yang H, Huang W, Liu S, Zhang H, Zhang X, Peng X. Chem. Soc. Rev.. 2025, 54341.
|
| [83] |
Zhao X, Du J, Sun W, Fan J, Peng X. Acc. Chem. Res.. 2024, 572582.
|
| [84] |
Yuan A, Qiu X, Tang X, Liu W, Wu J, Hu Y. Biomaterials. 2015, 51184.
|
| [85] |
Zhang Y, He X, Zhang Y, Zhao Y, Lu S, Peng Y, Lu L, Hu X, Zhan M. Chem. Eng. J.. 2021, 424130171.
|
| [86] |
Wang W, Zhang Y, Wang Z, Liu X, Lu S, Hu X. ACS Nano. 2023, 1711023.
|
| [87] |
Wang Y, Niu G, Zhai S, Zhang W, Xing D. Nano Research. 2020, 13719.
|
| [88] |
Li X, Kwon N, Guo T, Liu Z, Yoon J. Angew. Chem. Int. Ed.. 2018, 5711522.
|
| [89] |
Lin R, Liu J, Xu W, Liu Z, He X, Zheng C, Kang M, Li X, Zhang Z, Feng H-T, Lam J W Y, Wang D, Chen M, Tang B Z. Adv. Mater.. 2023, 352303212.
|
| [90] |
Xiao Q, Lin H, Wu J, Pang X, Zhou Q, Jiang Y, Wang P, Leung W, Lee H, Jiang S, Yao SQ, Gao L, Liu G, Xu C. J. Med. Chem.. 2020, 634896.
|
| [91] |
Wang Z, Ma W, Yang Z, Kiesewetter D O, Wu Y, Lang L, Zhang G, Nakuchima S, Chen J, Su Y, Han S, Wu L-G, Jin A J, Huang W. J. Am. Chem. Soc.. 2024, 14628973.
|
| [92] |
Yao C, Li Y, Wang Z, Song C, Hu X, Liu S. ACS Nano. 2020, 141919.
|
| [93] |
Tan J, Zhang J, Chen M, Cen J, Wang W, You C, Hu X, Hu J, Liu S. Angew. Chem. Int. Ed.. 2026, 65e22563.
|
RIGHTS & PERMISSIONS
Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH
PDF
