pH/Redox‐Triggered Photothermal Treatment for Cancer Therapy Based on a Dual‐Responsive Cationic Polymer Dot

• Published in: ChemMedChem Vol. 13; no. 22; pp. 2437 - 2447
• Main Authors: Mazrad, Zihnil Adha Islamy, Phuong, Pham Thi My, Choi, Cheong A., In, Insik, Lee, Kang Dae, Park, Sung Young
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 20.11.2018
• Subjects: Biodegradation; Cancer; Cancer therapies; cationic polymer dots; Cationic polymerization; Cytoplasm; Degradability; drug delivery; Endocytosis; Endosomes; Fluorescence; Folic acid; Glutathione; Hydrophobicity; Intracellular; Irradiation; Nanoparticles; Near infrared radiation; pH effects; Polyethyleneimine; Radiation; redox chemistry; Restoration; Therapy; Tumors; cationic polymer dots; cancer; nanoparticles; drug delivery; redox chemistry
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.201800538

In the present study, a pH/redox‐responsive cationic polymer dot (CD) was successfully prepared for a near‐infrared (NIR)‐mediated, simultaneously controllable photothermal temperature guided imaging off/on system to monitor therapeutic delivery. Carbonized disulfide cross‐linked branched polyethyleneimine (bPEI) was conjugated with folic acid (FA) as a targeting moiety and partially formed an ionic complex with anionic indocyanine green (ICG) to afford a bPEI‐based CD (ICG‐CD). This was responsive to mild reductive (glutathione, GSH) and acidic tumor conditions, which enabled the simultaneous biodegradation of those hydrophobic and complex sites. The ICG‐CD internalized readily into the cytoplasm of cancer cells by a FA receptor and cationic‐mediated endocytosis in the off state, whereas if ICG‐CD met intracellular GSH at high concentrations, GSH contributed partially to the recovery of fluorescence and was then internalized into acidic endosomes to induce complete restoration of fluorescence. This tumor‐sensitive degradability of the CD not only facilitated ICG release in the tumor location but also allowed controllable photothermal therapy effects of nanoparticles under NIR irradiation, which resulted in improved cancer therapy. Taken together, the results indicate great potential in tumor targeting, intracellular imaging, and controllable therapeutic delivery through a fluorescence off/on assay under the pH/redox conditions of cancer cells. On the dot: A pH/redox‐sensitive cationic polymer dot loaded with indocyanine green (ICG) was synthesized for a photothermal temperature guided imaging off/on system. The nanoparticles were internalized into the cytoplasm of cancer cells by folic acid receptor and cationic mediated endocytosis. Upon reaching the tumor sites, the high thermal energy released from ICG could be controlled to induce cancer cell death under near‐IR (NIR) irradiation. PTT=photothermal therapy.