期刊
SMALL
卷 17, 期 13, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202007882
关键词
colorectal cancer; combinatory immunotherapy; immunogenic cell death; prodrug nanoparticles; second near‐ infrared fluorescence imaging
类别
资金
- National Natural Science Foundation of China [51873228, 22074043]
- International Cooperation Project of Science and Technology Commission of Shanghai Municipality [20430711800]
- Youth Innovation Promotion Association of CAS [2014218]
- China Postdoctoral Science Foundation [2019M661667, 2020M681429]
- Shanghai Post-Doctoral Excellence Program
- Shanghai Institute of Materia Medica, CAS [FU-SIMM-20182006]
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, CAS
- Fudan University [FU-SIMM-20182006]
A versatile prodrug nanoparticle for second near-infrared (NIR-II) fluorescence imaging-guided combinatory immunotherapy of colorectal cancer has been reported. The nanoparticles show high intratumoral accumulation and trigger immunogenic cell death of the tumor cells, elicit antitumor immune response in a spatiotemporally controllable manner. The combination of the nanoparticle-based photothermal therapy/chemotherapy with programmed death ligand 1 blockade significantly promotes intratumoral infiltration of cytotoxic T lymphocytes and eradicates CRC tumors.
Colorectal cancer (CRC) ranks as the third common and the fourth lethal cancer type worldwide. Immune checkpoint blockade therapy demonstrates great efficacy in a subset of metastatic CRC patients, but precise activation of the antitumor immune response at the tumor site is still challenging. Here a versatile prodrug nanoparticle for second near-infrared (NIR-II) fluorescence imaging-guided combinatory immunotherapy of CRC is reported. The prodrug nanoparticles are constructed with a polymeric oxaliplatin prodrug (PBOXA) and a donor-spacer-acceptor-spacer-donor type small molecular fluorophore TQTCD. The later displays large Stokes shift (>300 nm), fluorescence emission over 1000 nm, and excellent photothermal conversion performance for NIR-II fluorescence imaging-guided photothermal therapy (PTT). The prodrug nanoparticles show seven times higher intratumoral OXA accumulation than free oxaliplatin. TQTCD-based PTT and PBOXA-induced chemotherapy trigger immunogenic cell death of the tumor cells and elicit antitumor immune response in a spatiotemporally controllable manner. Further combination of the prodrug nanoparticle-based PTT/chemotherapy with programmed death ligand 1 blockade significantly promotes intratumoral infiltration of the cytotoxic T lymphocytes and eradicates the CRC tumors. The NIR-II fluorescence imaging-guided immunotherapy may provide a promising approach for CRC treatment.
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