pH/thermal dual-responsive multifunctional drug delivery system for effective photoacoustic imaging-guided tumor chemo/photothermal therapy.

The development of a combination of chemo/photothermal therapy could overcome the limitations of single-modality therapy and enhance therapeutic efficacy. In this study, a pH/thermal dual-responsive multifunctional drug delivery system with dual-drug loading and enhanced chemo/photothermal therapy is developed based on polydopamine-coated mesoporous silica-gold nanorods (PDA-AuNRs@MSN). Nanoscale mesoporous silica-gold nanorods encapsulating doxorubicin (DOX) are designed as a core and then modified by polydopamine. The PDA shell not only conjugates with another anticancer bortezomib (Btz) to form pH-sensitive bond through boronic acid and catechol but also acts as a gatekeeper to control the release of doxorubicin and enhance the photothermal effect. Such a nanocarrier not only acts as a contrast agent for PA imaging but also serves as a therapeutic agent for enhanced chemo/photothermal therapy. The DOX and Btz could be released in an on-demand mode under near-infrared light irradiation and acid environment. The tumor size and location could be observed via PA imaging after intravenous injection into 4T1-bearing mice. Compared with AuNRs@MSN, PDA-AuNRs@MSN exhibit an increased near-infrared (NIR) absorption at 808 nm and an enhanced photothermal effect. The integrated D/B-PDA-AuNRs@MSN nanoparticles show higher cell apoptosis and enhanced tumor treatment efficacy in vitro and in vivo in comparison with single chemotherapy or photothermal therapy. Combined together, D/B-PDA-AuNRs@MSN show pH/thermal-responsive controlled-release and synergistic chemo/photothermal therapy for tumor.