Nanoplatform for Cancer Therapy

Abstract

Researchers at the University of California, Davis have developed a nanoparticle system combining photothermal therapy and chemotherapy for enhanced cancer treatment.

Full Description

Amphiphilic hybrid telodendrimers comprised of PEG, cholic acid and indocyanine green derivative (PCI) can self-assemble to form stable micelles, with excellent photothermal properties as well as high loading of cytotoxic agents and immunomodulatory agents. Introduction of a related cysteine containing telodendrimer allows co-assembly with PCI to form a biocompatible and stable disulfide-crosslinked PCI nanoparticle (CPCI-NPs). CPCI-NPs possess fast heating capability and superior photothermal conversion efficiency, when compared to small-molecule photothermal agents or gold nanorods. Combination photothermal-/chemo-therapy with doxorubicin-loaded CPCI-NPs resulted in highly synergistic anti-tumor response in orthotropic OSC-3 oral cancer xenograft model. Similarly, CPCI loaded with imiquimod, an immunostimulant, was found to be highly effective in 4T1 syngeneic murine breast cancer model, particularly when photothermal-/immuno-therapy was given in combination with PD-1 checkpoint blockade antibody. Such triple therapy not only eradicated the light-irradiated primary tumors, but also dramatically inhibited the light-untreated distant tumors via activating the innate and adaptive immune systems in the tumor microenvironment. This versatile photothermal nanoplatform has great potential for clinical translation.

Applications

• Cancer therapy, specifically for treating tumors accessible to light irradiation and potentially for systemic treatment when combined with immunotherapy.
• Photothermal ablation of localized tumors. 
• Controlled drug delivery systems for chemotherapeutic agents. 
• Diagnostic imaging through near-infrared fluorescence capabilities.

Features/Benefits

• High photothermal conversion efficiency for effective tumor ablation. 
• Stable and controlled drug release mechanism, enhancing chemotherapy efficacy. 
• Excellent biocompatibility and low systemic toxicity. 
• Enhanced tumor targeting and penetration, maximizing therapeutic outcomes. 
• Ability to combine photothermal therapy and chemotherapy, offering a synergistic therapeutic effect. 
• Overcomes limitations of poor drug solubility and systemic toxicity in chemotherapy. 
• Addresses the challenge of achieving targeted and controlled delivery of therapeutic agents to tumor sites. 
• Solves the issue of rapid clearance and low photothermal conversion efficiency seen in other photothermal agents.

Patent Status