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

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Materials Science

Background:

• Developing integrated diagnostic and therapeutic nanoplatforms with biodegradability is crucial for advanced cancer treatment.
• Current nanotheranostics often lack combined imaging, therapy, and responsive degradation capabilities.

Purpose of the Study:

• To create a biodegradable nanotheranostic agent for multimodal imaging-guided combination therapy.
• To evaluate the efficacy of the nanoplatform in inhibiting heat shock protein 90 (Hsp90) and its therapeutic potential.

Main Methods:

• Fabrication of hollow mesoporous organosilica nanoparticles (HMONs) encapsulating an Hsp90 inhibitor (17AAG).
• Pore-engineering with bovine serum albumin-iridium oxide nanoparticles (BSA-IrO2) and polyethylene glycol (PEG) conjugation to create AHBIP nanotheranostics.
• Evaluation of photothermal conversion efficiency, drug loading, stimuli-responsive release, and catalytic activity for photodynamic therapy (PDT) and photothermal therapy (PTT).

Main Results:

• AHBIP nanotheranostics demonstrated high photothermal conversion efficiency and cargo loading (35.4% for 17AAG).
• Stimuli-responsive release of 17AAG effectively inhibited Hsp90, inducing apoptosis at low temperatures (≈41 °C).
• IrO2 component provided catalytic activity for H2O2 decomposition, generating O2 to reduce tumor hypoxia and protect normal tissues. Synergistic PTT/PDT showed significant therapeutic outcomes in vitro and in vivo.

Conclusions:

• The developed AHBIP nanoplatform offers integrated diagnostic and therapeutic functions with intrinsic biodegradability.
• BSA-IrO2 and biodegradable HMONs incorporation shows significant potential for clinical applications in cancer theranostics.