NIR‐Triggered Phototherapy and Immunotherapy via an Antigen‐Capturing Nanoplatform for Metastatic Cancer Treatment

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.

Activating Antitumor Immunity and Antimetastatic Effect Through Polydopamine‐Encapsulated Core–Shell Upconversion Nanoparticles

“…This dual‐modal phototherapy can also boost memory T cell activation, which is essential for the prevention of tumor relapse. Our study sheds light on the immunological aspects of combinatorial phototherapy and broadens the scope of synergistic phototherapy‐based antitumor immunity, tumor metastasis suppression, and relapse prevention …”

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

“…A safe and effective immunotherapy with great controllability and sensitivity can be achieved by developing novel drug delivery platforms based on nanotechnology and material science. [264][265][266][267][268][269][270] The cascaded synergistic effects of photodynamic-immunotherapy can provide a promising strategy to inhibit both primary lesions and distant metastases, which can be hardly achieved by conventional PDT with limited immunologic effects. [256] Moreover, the combination of immunotherapy and PDT has attracted an increasing attention due to the potential systematic antitumor immunity after PDT.…”

Nanomedicine‐Based Immunotherapy for the Treatment of Cancer Metastasis

“…3 d before first vaccination, and also established a systemic antitumor immunity that protected the host from tumor rechallenge. [109][110][111] Instead of carrying cancer cellderived neoantigens with nanovaccines, Liu's lab induced immunogenic cell death (ICD) of tumor in situ with radiotherapy and potentiated immune response via simultaneous treatment of mice with imiquimod (R837)-loaded adjuvant nanoparticles and CTLA-4 checkpoint blockade, which inhibited the growth of abscopal metastasis sites. To further improve the efficacy of vaccination, Li and co-workers constructed a peptide-based hydrogel (Fmoc-KCRGDK (FK)) containing dead tumor cells loaded with JQ1 (a BRD4 inhibitor) and ICG (a photothermal agent) for local application in the site of tumor resection ( Figure 2C).…”