Gas-generating polymersomes-based amplified photoimmunotherapy for abscopal effect and tumor metastasis inhibition

Abstract

Due to the heterogeneity of tumors, single phototherapy cannot completely ablate tumors and inhibit tumor metastasis. To overcome these, we formulated targeted and multifunctional polymersomes ABC@ICG-IMQ-LHRH (AIRL) that encapsulated Toll-like receptor (TLR) 7/8 agonist imiquimod (IMQ) and photosensitizer indocyanine green (ICG) in the hydrophobic layer as well as bubble-generator NH4HCO3 in the hydrophilic cavity to inhibit the growth of primary and distant tumors, and prevent tumor metastasis through synergistic photoimmunotherapy. The AIRL polymersomes exhibited uniform and stable size, and high drug encapsulation efficiency, acid/reduction/laser responsiveness, excellent photothermal conversion efficiency, effective reactive oxygen species generation, high tumor accumulation. AIRL could be effectively internalized by dendritic cells (DCs), achieve lysosome escape and enhance DCs maturation. The synergistic photoimmunotherapy via AIRL polymersomes remarkably promoted the differentiation and activation of T cells, elevated strong systemic immune response to eradicate primary tumors and inhibit the growth of distant tumors. Simultaneously, the endurable immunological memory prevented tumor metastasis, which provided a promising nanoplatform for the combination therapy of cancer.