Double Drug-Loaded and pH/Thermal Sensitive Multifunctional Drug Delivery System for Tumor Photoacoustic Imaging-Guided Enhanced Chemo/Photothermal Therapy

Abstract Background: Owing to the tunability of longitudinal surface plasmon resonance (LSPR), ease of synthesizing small size and excellent stability, AuNRs have been developed as photothermal agents for cancer therapy. However, PTT alone could not kill cancer cells completely due to the local heterogeneous distribution of heat in tumors, penetration depth of light, light scattering and absorption. In addition, the treatment systems based on AuNRs hold disadvantages of loading one antitumor drug or a low therapeutic efficiency. Therefore, the construction of the AuNRs theranostic system to achieve imaging-guided dual drug delivery and enhanced photothermal therapy for tumor still remains a great challenge.Methods: The AuNRs were prepared using a seedless method. A mesoporous silica shell layer was coated on the surface of the AuNRs by sol-gel method. Double anticancer drugs, DOX and Btz, were loaded into the AuNRs@MSN nanoparticles through physical absorption and covalent conjugation, respectively.Results: The release of DOX and Btz is found pH/thermal dual responsive in vitro. Compared with AuNRs@MSN, PDA-AuNRs@MSN exhibits an increased near-infrared (NIR) absorption at 808 nm and an enhanced photothermal effect. In contrast to chemotherapy or photothermal therapy alone, the integrated D/B-PDA-AuNRs@MSN nanoparticles show higher cell apoptosis and enhanced tumor treatment efficacy in vitro and in vivo.Conclusions: In this study, we designed a double-drug loading, enhanced chemo/photothermal therapy and pH/thermal responsive drug delivery system for photoacoustic (PA) imaging-guided tumor therapy. We believe that the multifunctional D/B-PDA-AuNRs@MSN theranostic probe could serve as an effective probe for the treatment of cancers.