Many studies have focused on developing effective therapeutic
strategies
to selectively destroy primary tumors, eliminate metastatic lesions,
and prevent tumor recurrence with minimal side effects on normal tissues.
In this work, we synthesized engineered cellular nanovesicles (ECNVs)
with tumor-homing and immune-reprogramming functions for photoacoustic
(PA) imaging-guided precision chemoimmunotherapy. M1-macrophage-derived
cellular nanovesicles (CNVs) were loaded with gold nanorods (GNRs),
gemcitabine (GEM), CpG ODN, and PD-L1 aptamer. The good histocompatibility
and tumor-homing effect of CNVs improved drug retention in the bloodstream
and led to their enrichment in tumor tissues. Furthermore, the photothermal
ability of GNRs enabled PA imaging-guided drug release. GEM induced
tumor immunogenic cell death (ICD), and CpG ODN promoted an immune
response to the antigens released by ICD, leading to long-term specific
antitumor immunity. In addition, the PD-L1 aptamer relieved the inhibitory
effect of the PD1/PD-L1 checkpoint on CD8+ T-cells and
augmented the immunotherapeutic effect. The synergistic innate and
adaptive immune responses enhanced the antitumor effect of ECNVs.
In summary, this nanoplatform integrates local targeted photothermal
therapy with extensive progressive chemotherapy and uses ICD to reshape
the immune microenvironment for tumor ablation.
Effective therapeutic strategies to precisely eradicate primary tumors with minimal side effects on normal tissue, inhibit metastases, and prevent tumor relapses, are the ultimate goals in the battle against cancer. We report a novel therapeutic strategy that combines adjuvant black phosphorus nanoparticle-based photoacoustic (PA) therapy with checkpoint-blockade immunotherapy. With the mitochondria targeting nanoparticle, PA therapy can achieve localized mechanical damage of mitochondria via PA cavitation and thus achieve precise eradication of the primary tumor. More importantly, PA therapy can generate tumor-associated antigens via the presence of the R848-containing nanoparticles as an adjuvant to promote strong antitumor immune responses. When combined with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4, the generated immunological responses will further promote the infiltrating CD8 and CD4 T-cells to increase the CD8/Foxp3 T-cell ratio to inhibit the growth of distant tumors beyond the direct impact range of the PA therapy. Furthermore, the number of memory T cells detected in the spleen is increased, and these cells inhibit tumor recurrence. This proposed strategy offers precise eradication of the primary tumor and can induce long-term tumor-specific immunity.
Electronic Supplementary Material
Supplementary material is available for this article at 10.1007/s12274-020-3028-x and is accessible for authorized users.
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