Triggered micelles for enhanced integration of chemotherapy and photodynamic therapy

• Grant number: 17/50126-1
• Support type: Regular Research Grants
• Duration: March 01, 2018 - February 29, 2020
• Field of knowledge: Engineering - Chemical Engineering - Chemical Technology
• Cooperation agreement: Tianjin University
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Simone de Fátima Medeiros Sampaio
• Grantee: Simone de Fátima Medeiros Sampaio
• Principal investigator abroad: Yanjun Zhao
• Institution abroad: Tianjin University (TJU), China
• Home Institution: Escola de Engenharia de Lorena (EEL). Universidade de São Paulo (USP). Lorena , SP, Brazil
• Associated research grant: 15/19651-7 - Development of solid formulations and entrapment of poor soluble active ingredients for topical and systemic applications, AP.R

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)