Triggered micelles for enhanced integration of chemotherapy and photodynamic therapy

Abstract

The combination of photodynamic therapy (PDT) and chemotherapy is one attractive regime for cancer medication. Nanoparticulate delivery of PDT/chemotherapy payloads involves the highly complex biological, chemical, and transport barriers, among which the rapid cargo release into cytoplasm is one critical step. The generation of traditional triggered-release nanocarriers often necessitates tedious material synthesis and complex fabrication procedure. It would be encouraging to generate simple "self-triggered" nanocarriers based on the dynamic payload- carrier interaction to realize rapid on-demand cargo release. The aim of this project is to engineer "self-triggered" polymer conjugate micellar nanocarrier for realization of on-demand micelle destabilization and rapid cargo release, and hence enhanced efficacy of PDT/chemotherapy combinational therapy. The hydrophilic shift of polymer conjugate's hydrophobic domain upon laser treatment would induce swift micelle de-assembly and rapid releeie of chemodrug and photosensitizer (PS). The following objectives have been identified to achieve these aims: (1) To synthesize and characterize a series of amphiphilic polymer-fatty acid conjugates; (2) To generate and optimize the micellar nanocarriers containing both chemodrug and PS; (3) To validate whether the PS-generated singlet oxygen could efficiently initiate lipid peroxidation, induce micelle collapse, and eventually facilitate rapid payload release and (4) To demonstrate the in vitro and in vivo efficacv of "self-triaaered" micellar nanocarriers. (AU)