Cascade Carrier‐Free Nanoparticles Forming In Situ Nanovaccines for Synergistic Photothermal‐Immunotherapy of Cancer

Abstract

Rapid advances in nanotechnology have made it possible to combine photothermal therapy (PTT) with immunotherapy, enabling to activate an in situ vaccine effect. However, this effect is severely impeded by low antigen presentation level and highly suppressive tumor immune microenvironment (immune “cold” tumors). To overcome the obstacles, multifunctional carrier‐free nanoparticles (FCDP‐NPs) assembled from Fe2+, toll‐like receptor 9 agonist (CpG), cationic lipid (DOTAP) and photothermal agent polydopamine are developed. After intratumoral injection, FCDP‐NPs carrying positive charge are exposed under laser irradiation, which can capture tumor‐associated antigens (TAAs) generated upon post‐PTT to form the nanovaccines (FCD‐NPs@TAAs). The nanovaccines further promote cross‐presentation of TAAs, stimulate adaptive immune responses, and shape immune “hot” tumors. As a result, in situ nanovaccines highly improve survival rates and elicit a durable immune memory that remarkedly prevents tumor metastasis, illustrating a useful platform for PTT synergized with immunotherapy.

Multifunctional Nanoparticle-Loaded Injectable Alginate Hydrogels with Deep Tumor Penetration for Enhanced Chemo-Immunotherapy of Cancer

“…After uptake by DCs, the internalized antigens enter the lysosome where they are processed into small peptides, and then activate CD4 + T cells by forming a complex with MHC II. 31 Antigens that enter the cytoplasm are further processed by proteasome into peptides and activate CD8 + T cells by forming a peptide-MHC I complex, which is important to evoke vigorous CTLs and form effective vaccines. 32 PEI can rupture lysosomes through the proton sponge effect, which has been demonstrated as a potent mechanism to increase the cytosolic release of antigens and cross-presentation.…”

“…As an important type of antigen-presenting cells (APCs), DCs mainly assume the role of antigen uptake and presentation, which are crucial in activating T cells. After uptake by DCs, the internalized antigens enter the lysosome where they are processed into small peptides, and then activate CD4 + T cells by forming a complex with MHC II . Antigens that enter the cytoplasm are further processed by proteasome into peptides and activate CD8 + T cells by forming a peptide-MHC I complex, which is important to evoke vigorous CTLs and form effective vaccines .…”

Emerging Cationic Nanovaccines

“…Combinatory therapy against cancer often represents a promising strategy. For example, photothermal therapy (PTT) and immunotherapy were combined in the design of a nanovaccine in situ; NPs were assembled from Fe 2+ , CpG agonist of toll-like receptor 9, cationic lipid and polydopamine (PTT agent); after intratumoral injection, the cationic NPs were exposed to laser light irradiation capturing the released antigens and generating the nanovaccines in situ; there was crosspresentation of tumoral antigens, increased adaptive immune responses, and change of the immunosuppressive tumor environment to immunoresponsive one;hence, in situ nanovaccines highly improved survival rates and elicited a durable immune memory that prevented tumor metastasis, illustrating the synergism for PTT combined with immunotherapy [205].…”