pH/Thermal-Sensitive Nanoplatform Capable of On-Demand Specific Release to Potentiate Drug Delivery and Combinational Hyperthermia/Chemo/Chemodynamic Therapy.

ABSTRACT

Therapeutic platforms with spatiotemporal control were recently of considerable interest. However, the site-specific regulation of chemotherapeutics release remains an enormous challenge. Herein, a versatile nanoplatform capable of tumor-specific delivery and controlled drug release, coined as PDDFe, was constructed for elevating cancer theranostics. Iron-oxide nanoparticles (IONPs) and doxorubicin (Dox) were encapsulated in pH/thermal-sensitive micelles composed of poly(ethylene)glycol-poly(ß-amino esters) and dipalmitoyl phosphatidylcholine to obtain tumor-targeted dual-responsive nanoplatforms. With remarkable magnetic targeting effects, PDDFe specifically accumulated at tumor locations. After internalization by cancer cells, the acidic environment and localized heat generated by hyperthermia therapy would spur PDDFe to become loose and collapse to liberate its payload. In addition to boosting the release, the increased temperature also resulted in direct tumor damage. Meanwhile, the released Dox and IONPs, respectively, stimulated chemotherapy and chemodynamic therapy to jointly destroy cancer, thus leading to a pronounced therapeutic effect. In vivo magnetic resonance/fluorescence/photoacoustic imaging experiments validated that the dual-sensitive nanoplatforms were able to accumulate at the tumor sites. Treatment with PDDFe followed by alternating magnetic field and laser irradiation could prime hyperthermia/chemo/chemodynamic therapy to effectively retard tumor growth. This work presents a nanoplatform with a site-specific controlled release characteristic, showing great promises in potentiating drug delivery and advancing combinational cancer therapy.