期刊
ADVANCED SCIENCE
卷 6, 期 10, 页码 -出版社
WILEY
DOI: 10.1002/advs.201802157
关键词
antigen capture; immunotherapy; metastatic cancer; phototherapy; upconversion
资金
- U.S. National Institutes of Health [R21 EB015509, RS20132225-106, R01 CA205348]
- National Key R&D Program of China [2018YFC0910602]
- National Natural Science Foundation of China [61775145, 61525503, 61620106016, 61835009, 81727804]
- China Postdoctoral Science Foundation [2018M633116]
- Guangdong Natural Science Foundation Innovation Team [2014A030312008]
Combined phototherapy and immunotherapy demonstrates strong potential in the treatment of metastatic cancers. An upconversion nanoparticle (UCNP) based antigen-capturing nanoplatform is designed to synergize phototherapies and immunotherapy. In particular, this nanoplatform is constructed via self-assembly of DSPE-PEG-maleimide and indocyanine green (ICG) onto UCNPs, followed by loading of the photosensitizer rose bengal (RB). ICG significantly enhances the RB-based photodynamic therapy efficiency of UCNP/ICG/RB-mal upon activation by a near-infrared (NIR) laser, simultaneously achieving selective photothermal therapy. Most importantly, tumor-derived protein antigens, arising from phototherapy-treated tumor cells, can be captured and retained in situ, due to the functionality of maleimide, which further enhance the tumor antigen uptake and presentation by antigen-presenting cells. The synergized photothermal, photodynamic, and immunological effects using light-activated UCNP/ICG/ RB-mal induces a tumor-specific immune response. In the experiments, intratumoral administration of UCNP/ICG/RB-mal, followed by noninvasive irradiation with an NIR laser, destroys primary tumors and inhibits untreated distant tumors, using a poorly immunogenic, highly metastatic 4T1 mammary tumor model. With the simultaneous use of anti-CTLA-4, about 84% of the treated tumor-bearing mice achieve long-term survival and 34% of mice develop tumor-specific immunity. Overall, this antigen-capturing nanoplatform provides a promising approach for the treatment of metastatic cancers.
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