Tumor Microenvironment-Responsive Nanocluster for Time-Resolved Hyperthermic Intraperitoneal Chemo/Thermal-Therapy...

Area of Science:

• Oncology
• Nanomedicine
• Drug Delivery Systems

Background:

• Peritoneal metastasis (PM) from gastrointestinal cancer presents significant therapeutic challenges due to its diffuse nature and poor drug penetration.
• Current hyperthermic intraperitoneal chemotherapy (HIPEC) offers survival benefits but is limited by systemic toxicity and cancer cell thermoresistance.

Purpose of the Study:

• To develop a tumor microenvironment-responsive nanocluster system (MoNs@MyC) for augmented HIPEC treatment of peritoneal metastasis.
• To enhance localized drug retention, synergize chemotherapy with secondary hyperthermia, and reduce systemic toxicity.

Main Methods:

• Development of ultrasmall monodispersed-nanoclusters (MoNs) loaded with mitomycin C (MyC).
• MoNs@MyC self-assembles into microsize particles in acidic tumor environments, enhancing drug retention during HIPEC.
• Utilized photothermal conversion for secondary hyperthermia and assessed mitigation of oxidative damage in healthy tissues.

Main Results:

• MoNs@MyC demonstrated enhanced localized drug retention and superior tumor control in peritoneal metastasis mouse models compared to conventional HIPEC.
• The system effectively combined chemotherapy with photothermal hyperthermia, overcoming cancer cell thermoresistance.
• MoNs@MyC selectively reduced mitomycin C-induced oxidative damage in healthy tissues and stimulated antitumor immunity.

Conclusions:

• The dual-responsive MoNs@MyC system represents a transformative strategy for precision peritoneal metastasis therapy.
• This approach improves localized treatment efficacy while enhancing systemic safety, bridging a critical gap in current therapies.
• Scalable synthesis and cost-effective design support its potential clinical translation for peritoneal metastasis.