Multifunctional layered zinc oxide nanocomposites for combination cancer therapy

초록

Therapeutic nanocomposites activated by the tumor microenvironment (TME) mark a significant shift in cancer therapy. Despite their promise, structural instability, limited functionalities, and lack of synergy hinder the achievement of targeted multifunctionality in these composites. The current study proposes a TME-responsive and all-immuno-functional nanocomposite for a combinatory immunotherapy strategy that synchronizes the multi-immune functionality of zinc oxide nanoparticles (ZnO NPs) with anticancer antigen-presenting cell (APC) immunity. We develop a simple yet effective nano-networking process through assembling double-stranded RNA (dsRNA) adjuvant poly I:C, 4 nm ZnO NPs, and recombinant ovalbumin protein (OVA) in a layer-by-layer fashion to create a virus-mimetic structure. Structural stability enhances cancer cell-specific apoptosis, thereby facilitating the follow-up TME-responsive immunological function of the nanocomposite and thereby eliciting both local and systemic immune responses. Combination therapy with anti-CD47 blockade further inhibits the 'don't eat me' signaling in the cancer cell-APC interaction, collaboratively augmenting therapeutic efficacy in a B16 mouse melanoma model.

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