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

Abstract 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‐IrO 2 ) and conjugation of polyethylene glycol (PEG) is conducted to yield 17AAG@HMONs‐BSA‐IrO 2 ‐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 IrO 2 simultaneously endows the nanotheranostics with catalytic activity in triggering the decomposition of H 2 O 2 into O 2 and thus reducing the tumor hypoxia, as well as protecting normal tissues against H 2 O 2 ‐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‐IrO 2 and biodegradable HMONs into one nanoplatform has great potential for clinical applications.