Biodegradable theranostic nanoplatforms of albumin-biomineralized nanocomposites modified hollow mesoporous organosilica for photoacoustic imaging guided tumor synergistic therapy

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.