A Tumor Microenvironment-Responsive Biodegradable Mesoporous Nanosystem for Anti-Inflammation and Cancer Theranostics

A nanoplatform that integrates diagnostic and therapeutic functions with intrinsic tumor microenvironment-responsive biodegradability is highly desired. Herein, a biodegradable nanotheranostic agent based on hollow mesoporous organosilica nanoparticles (HMONs), followed by encapsulating of heat shock protein 90 (Hsp 90) inhibitor is described. Then, the pore-engineering including gating with bovine serum albumin-iridium oxide nanoparticles (BSA-IrO₂ ) and conjugation of polyethylene glycol (PEG) is conducted to yield 17AAG@HMONs-BSA-IrO₂ -PEG (AHBIP) nanotheranostics for multimode computed tomography (CT)/photoacoustic (PA) imaging-guided photodynamic therapy (PDT) and low-temperature photothermal therapy (PTT). Such nanoplatforms show extraordinary photothermal conversion efficiency, high cargo loading (35.4% for 17AAG), and stimuli-responsive release of 17AAG for inhibition of Hsp90, which induces cell apoptosis at low-temperatures (≈41 °C). Also, the IrO₂ simultaneously endows the nanotheranostics with catalytic activity in triggering the decomposition of H₂ O₂ into O₂ and thus reducing the tumor hypoxia, as well as protecting normal tissues against H₂ O₂ -induced inflammation. AHBIP shows good photocatalysis activity for PDT as a result of the generation of superoxide anion by laser irradiation. The resulting AHBIP-mediated synergistic PTT/PDT offers an outstanding therapeutic outcome both in vitro and in vivo. Overall, the incorporation of the BSA-IrO₂ and biodegradable HMONs into one nanoplatform has great potential for clinical applications.