Sequential release of drugs from dual-delivery plasmonic nanogels containing lipid-gated mesoporous silica-coated gold nanorods

Nanosystems that enable the sequential delivery of various drugs with different targets are desired for improved cancer therapy. However, current strategies are mainly dependent on the tumour microenvironment, such as low pH or enzyme -triggered release. In this work, a nanosystem design strategy for near infrared (NIR) light -triggered sequential delivery based on lipid -gated mesoporous silica -coated gold nanorods and chitosan/alginate nanogels was developed. The mesoporous silica particles (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. The plasmonic nanogels exhbited high loading efficiencies of -90 % and -85 for methotrexate and doxorubicin, respectively. Notably, this system displayed average hydrodynamic diameters near 300 nm, low polidispersity, highly negative zeta potential (--30 mV), and a sustained release of both drugs under acidic and neutral conditions. Upon NIR laser irradiation, an enhanced release of both drugs was observed, with doxorubicin exhibiting a faster release rate than methotrexate under acidic conditions. This design strategy of NIR-triggered sequential delivery holds promise for different drug combinations against multiple targets in tumour microenvironment in the field of multimodal cancer therapy.