Abstract
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.
Highlights
Introduction the treatment of metastatic cancersAn upconversion nanoparticle (UCNP) based antigen-capturing nanoplatform is designed to synergize phototherapies and immunotherapy
These results demonstrate that UCNP/indocyanine green (ICG)/rose bengal (RB)-mal based phototherapy could significantly kill 4T1 tumor cells while enhancing the release of tumor-derived protein antigens (TDPAs)
These results indicate that UCNP/ICG/RB-mal based phototherapy effectively induced differentiation of T cells to CD8+ T cells and significantly improved the intratumoral CD8+ T cell ratios
Summary
Compared to UCNP-mal, the upconversion luminescence (UCL) intensity of UCNP/ICG-mal showed a twofold enhancement (Figure 2d). Both the vis–NIR absorption spectrum and emission spectrum showed an overlap between the RB absorbance band and the green emission peaks of UCNP (Figure S4, Supporting Information). Increased 1O2 production was observed in 4T1 cells after incubation with UCNP/ICG/RB-mal, followed by an 805 nm laser irradiation (3 min, 0.75 W cm−2), as measured through the fluorescence emission of the reactive oxygen species (ROS) probe (DCFH-DA) (Figure 2h). Infrared thermal images were acquired to verify the UCNP/ICG/ RB-mal + laser (L) induced temperature increase (Figure S5, Supporting Information)
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