journal article·2025-11Open access

PD‐L1‐Targeting Biomimetic Photoresponsive Thermosensitive Liposomes for Triple‐Negative Breast Cancer

Manman Tan, Chengyu Shi, Guangyi Chi, Xinwan Su, Fangzhou Liu, Linyu Zhu, Guangqian Cheng, Xiangyi Chen, Meng Yu, Yijian Chen, Ying Wang, Yu Chen, ShuLing Yan, Wenfei Wu, Qingfeng Yan, Jianzhong Shao, Kai Wang, Xiangrui Liu, Min Zhou, Aifu Lin

Advanced Science· Volume 12· Issue 41

Abstract

Abstract Peptide‐based therapeutic strategies offer considerable potential for tumor immunotherapy but suffer from poor systemic bioavailability, rapid plasma clearance, and limited tumor‐targeting efficiency. To address these challenges, a biomimetic, photothermal‐responsive liposomal delivery system was developed that enables precise delivery of immunotherapeutic peptides while enhancing the synergistic effects of photothermal therapy. This system enhances peptide stability through fluorination, disrupts post‐translational modifications of PD‐L1, and promotes its degradation, thereby amplifying the anti‐tumor immune response. The carrier core consisted of thermosensitive 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine (DPPC) liposomes loaded with the low‐toxicity photosensitizer indocyanine green (ICG), which facilitated controlled peptide release via the photothermal effect. Simultaneously, mild photothermal stimulation induced immunogenic cell death (ICD), further strengthening anti‐tumor immunity. To enhance tumor targeting, extend systemic circulation time, and improve drug accumulation at tumor sites, the carrier surface was coated with a platelet membrane, which increased biocompatibility and promoted immune evasion. Notably, in vivo studies demonstrated that the developed bioengineering platform significantly suppressed tumor growth in both solid and diffuse malignant tumors while inducing persistent immune memory, thereby facilitating long‐term anti‐tumor immune responses. Collectively, this approach establishes a novel framework for integrating peptide drug delivery with photothermal therapy, offering a promising strategy for advancing tumor immunotherapy.
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Research context

OpenAlex topics: Nanoplatforms for cancer theranostics · Nanoparticle-Based Drug Delivery · Advanced biosensing and bioanalysis techniques

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

MOE Laboratory of Biosystem Homeostasis and Protection College of Life Sciences Zhejiang University Hangzhou Zhejiang 310000 China

Key Laboratory of RNA Science and Engineering Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China

Department of Respiratory and Critical Care Medicine Center for Oncology Medicine the Fourth Affiliated Hospital of School of Medicine and International School of Medicine International Institutes of Medicine Zhejiang University Zhejiang 322000 China

Zhejiang Key Laboratory of Precision Diagnosis and Treatment for Lung Cancer Yiwu 322000 China

Key Laboratory of Cancer Prevention and Intervention The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310000 China

Department of Pharmacology, and Department of Gastroenterology of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310000 China

Future Health Laboratory Innovation Center of Yangtze River Delta Zhejiang University Jiashan Zhejiang 314102 China

Zhejiang University‐University of Edinburgh Institute Zhejiang University School of Medicine Haining Zhejiang 314400 China

Cancer Center Zhejiang University Hangzhou Zhejiang 310000 China

Funding

National Science Fund for Distinguished Young Scholars · National Key Research and Development Program of China · Fundamental Research Funds for the Central Universities · National Natural Science Foundation of China

References (67)

Show source-provided references
1. 10.1038/s41573-020-00135-810.1038/s41573-020-00135-8 ↗
2. 10.1136/bmj-2024-08012210.1136/bmj-2024-080122 ↗
3. 10.1039/D1SC05662J10.1039/D1SC05662J ↗
4. 10.1056/NEJMoa240366410.1056/NEJMoa2403664 ↗
5. 10.1002/mco2.4810.1002/mco2.48 ↗
6. 10.1038/s41551-019-0375-610.1038/s41551-019-0375-6 ↗
7. 10.1021/jacs.1c0813210.1021/jacs.1c08132 ↗
8. 10.1038/s41419-020-03086-510.1038/s41419-020-03086-5 ↗
9. 10.1038/s41598-018-28339-410.1038/s41598-018-28339-4 ↗
10. 10.1002/iid3.87910.1002/iid3.879 ↗
11. 10.7717/peerj.1633410.7717/peerj.16334 ↗
12. 10.1016/j.omto.2020.06.00510.1016/j.omto.2020.06.005 ↗
13. 10.1111/febs.1553910.1111/febs.15539 ↗
14. 10.1038/s41467-022-34346-x10.1038/s41467-022-34346-x ↗
15. 10.1021/acs.jmedchem.7b0031810.1021/acs.jmedchem.7b00318 ↗
16. 10.1007/s10989-023-10524-310.1007/s10989-023-10524-3 ↗
17. 10.3390/ph1509107210.3390/ph15091072 ↗
18. 10.1016/S0021-9258(17)40291-210.1016/S0021-9258(17)40291-2 ↗
19. 10.1021/acsnano.1c0592210.1021/acsnano.1c05922 ↗
20. 10.1016/j.jconrel.2016.06.04010.1016/j.jconrel.2016.06.040 ↗
21. 10.1021/acs.jmedchem.5b0072610.1021/acs.jmedchem.5b00726 ↗
22. 10.1016/j.ejpb.2015.09.00110.1016/j.ejpb.2015.09.001 ↗
23. 10.1530/EJE-17-107310.1530/EJE-17-1073 ↗
24. 10.1021/acs.bioconjchem.8b0046310.1021/acs.bioconjchem.8b00463 ↗
25. 10.1016/j.jconrel.2018.12.03210.1016/j.jconrel.2018.12.032 ↗
26. 10.1021/acs.accounts.1c0076610.1021/acs.accounts.1c00766 ↗
27. 10.3390/foods1312194310.3390/foods13121943 ↗
28. 10.1016/j.bmc.2017.08.03110.1016/j.bmc.2017.08.031 ↗
29. 10.1002/anie.20241634810.1002/anie.202416348 ↗
30. 10.1126/sciadv.aaz177410.1126/sciadv.aaz1774 ↗
31. 10.1039/D0CS00258E10.1039/D0CS00258E ↗
32. 10.1038/s41467-018-03779-810.1038/s41467-018-03779-8 ↗
33. 10.1002/cjoc.20200065510.1002/cjoc.202000655 ↗
34. 10.1002/smll.20190093610.1002/smll.201900936 ↗
35. 10.1126/scitranslmed.aaz728710.1126/scitranslmed.aaz7287 ↗
36. 10.1016/j.semarthrit.2008.08.00410.1016/j.semarthrit.2008.08.004 ↗
37. 10.1111/ijfs.1711010.1111/ijfs.17110 ↗
38. 10.1016/j.ijbiomac.2021.01.15210.1016/j.ijbiomac.2021.01.152 ↗
39. 10.1016/j.biomaterials.2017.08.04510.1016/j.biomaterials.2017.08.045 ↗
40. 10.2147/IJN.S44287710.2147/IJN.S442877 ↗
41. 10.1016/j.apsb.2022.08.01310.1016/j.apsb.2022.08.013 ↗
42. 10.1007/s40820-019-0330-910.1007/s40820-019-0330-9 ↗
43. 10.1021/acs.bioconjchem.6b0056910.1021/acs.bioconjchem.6b00569 ↗
44. 10.1002/adma.20160620910.1002/adma.201606209 ↗
45. 10.1002/adma.20221020110.1002/adma.202210201 ↗
46. 10.1002/adhm.20230356810.1002/adhm.202303568 ↗
47. 10.1002/adma.20210464110.1002/adma.202104641 ↗
48. 10.1038/s41467-020-17380-510.1038/s41467-020-17380-5 ↗
49. 10.1158/0008-5472.CAN-18-160410.1158/0008-5472.CAN-18-1604 ↗
50. 10.1083/jcb.20180416110.1083/jcb.201804161 ↗
51. 10.3390/polym1206139710.3390/polym12061397 ↗
52. 10.1016/j.colsurfb.2024.11374310.1016/j.colsurfb.2024.113743 ↗
53. 10.1002/anie.20242237510.1002/anie.202422375 ↗
54. 10.1002/adma.20200600310.1002/adma.202006003 ↗
55. 10.3390/pharmaceutics1002005710.3390/pharmaceutics10020057 ↗
56. 10.3390/jfb1601001510.3390/jfb16010015 ↗
57. 10.1002/anie.20230008510.1002/anie.202300085 ↗
58. 10.1002/advs.20220529410.1002/advs.202205294 ↗
59. 10.1182/blood.201900411910.1182/blood.2019004119 ↗
60. 10.1002/adma.20190079510.1002/adma.201900795 ↗
61. 10.1016/j.apsb.2023.02.00910.1016/j.apsb.2023.02.009 ↗
62. 10.1016/j.apsb.2017.11.00910.1016/j.apsb.2017.11.009 ↗
63. 10.1038/ncomms1319310.1038/ncomms13193 ↗
64. 10.1038/s41467-022-30306-710.1038/s41467-022-30306-7 ↗
65. 10.1186/s12951-021-01080-310.1186/s12951-021-01080-3 ↗
66. 10.1002/smll.20220549810.1002/smll.202205498 ↗
67. 10.1016/j.nantod.2021.10135910.1016/j.nantod.2021.101359 ↗