Intracellular Co-delivery of native antibody and siRNA for combination therapy by using biodegradable silica nanocapsules.

ABSTRACT

Combination therapy is a promising strategy for treating multidrug-resistant (MDR) cancers. Macromolecules such as antibodies and RNAs have been successfully used for targeted therapy owing to their high specificity. However, their application as therapeutics remains limited due to membrane impermeability and poor intracellular stability. Designing drug delivery systems capable of co-administering macromolecules is therefore crucial for advancing them as therapeutics for combination therapy. Herein, by using glutathione (GSH)-responsive biodegradable silica nanocapsules (BS-NPs), we report for the first time a highly versatile nanomaterial-based strategy for co-encapsulation and intracellular co-delivery of different combinations of macromolecules (i.e., siRNA/protein, siRNA/antibody and protein/antibody). This strategy was successfully used in the intracellular co-delivery of siRNA/Cetuximab (also named Erbitux™) for combination therapy in epidermal growth factor receptor (EGFR)-overexpressing cancer cells. These BS-NPs showed good biosafety profiles and antitumor efficacy when administered in vivo, suggesting that the strategy holds potential as a novel delivery platform for combination cancer therapy.