Abstract
Benefit from the integration of therapeutic and diagnostic functions, theranostic nanoplatforms have attracted widespread attention in preclinical research. Herein, a biodegradable theranostics nanoplatform based on hollow mesoporous organosilica nanoparticles (HMONs) is designed for highly efficient photoacoustic (PA) imaging guided chemo-photothermal therapy (PTT) of human osteosarcoma cancer. In this design, HMONs with intrinsic tumor microenvironment-responsive biodegradability were served as carrier for doxorubicin (DOX) loading. Then, biocompatible nanocomposites (CuS@BSA) with excellent photothermal conversion efficiency and inherent biocompatibility were prepared via a facile biomineralization strategy and are first decorated on the surface of HMONs through a GSH-sensitive disulfide bond (denoted as CuS@BSA-HMONs-DOX). The obtained CuS@BSA-HMONs provides a high DOX loading capacity of 42.9%. The fabricated theranostic nanosystems exhibit GSH-responsive breakage of the incorporated disulfide bonds in the framework of HMONs and the linker between HMONs and BSA, which leads to the release of loaded DOX and tumor-specific biodegradation. With the strong absorbance in near-infrared (NIR) region, CuS@BSA-HMONs-DOX nanoparticles show excellent diagnostic performance on the PA imaging modalities. Upon NIR laser irradiation, the introduction CuS endows the nanotheranostics have high photothermal conversion efficiency of 51.5% for hyperthermia. Also, the resulting CuS@BSA-HMONs-DOX exhibited pH-, NIR- and GSH-sensitive drug release, realizing synergistic chemo-phototherapy functions. Besides, the NIR laser-triggered mild hyperthermia can significantly enhance the cell uptake of nanoparticles. As validated by in vivo and in vitro assays, our CuS@BSA-HMONs-DOX can effectively delivers drug to tumor sites/cancer cells and induce the mild hyperthermia, resulting in an enhanced suppression of tumor growth. Combined with the excellent biocompatibility and biodegradability, the presented “all-in-one” nanotheranostics may provide an innovative paradigm for imaging guided and synergistic treatments.
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