New strategies for multimodal cancer therapy based on plasmonic lipogels

Abstract

Enhancing the therapeutic efficacy of chemotherapeutic agents through sequential drug delivery holds immense promise, yet current strategies are mainly dependent on the tumour microenvironment. Natural polymer-based hydrogels present suitable properties for these applications, owing to their inherent biocompatibility [1]. Herein, we present a novel strategy aimed at improving the tunability and real-time control of nanogels, as well as enabling compartmentalization of drugs for on-demand release using NIR light [2]. We hypothesized that combining chitosan/alginate nanogel with lipid-gated mesoporous silica-coated gold nanorods, thus obtaining plasmonic lipogels [3], could enable both the drug loading in different compartments and the sequential release of two chemotherapeutic drugs (doxorubicin and methotrexate). Hence, mesoporous silica-coated gold nanorods (99 ± 11 nm) were loaded with methotrexate, and further coated with a thermoresponsive phospholipid bilayer that works as gatekeeper. These particles were then incorporated in a chitosan/alginate nanogel matrix containing doxorubicin (Figure 1). The nanogels exhibited high loading efficiencies of ~90% and ~85% for methotrexate and doxorubicin, respectively. Notably, the exposure to NIR laser irradiation led to an enhanced release of both drugs, in which doxorubicin released at a faster rate than methotrexate under acidic conditions. Besides, the plasmonic nanogels were found to be cytocompatible across different cell lines. Hereby, this design strategy presents a robust and multifunctional hydrogel platform for NIR-triggered sequential delivery that holds promise for advancing cancer therapy through different drug combinations against multiple targets in tumour microenvironment.