Self-assembled polymeric micelles for targeted photodynamic therapy of human epidermal growth factor receptor 2 overexpressing breast cancer.

Abstract

Photodynamic therapy (PDT) has been extensively explored as a promising alternative therapeutic approach for many malignant tumors. However, the PDT system generally involves unsatisfactory tumor specificity and nonspecific accumulation of photosensitizers around the target cancer cells, leading to phototoxic damage to adjacent healthy normal cells. In this study, we developed pheophorbide a (Pheo a)/human epidermal growth factor receptor 2 (HER2) targeting peptide (epitope form, HLTV, PEG2-LTVSPWY)-co-conjugated methoxy poly(ethylene glycol)-block-poly(L-lysine hydrochloride) (PEG-PLL)/hyaluronic acid (HA) (P3H2) polymeric micelles via a self-assembly method for HER2-targeted PDT treatment for breast cancer, thereby enhancing the PDT efficacy. The synthesized P3H2 polymeric micelles were spherical, with an average diameter of 125.7 ± 21.2 nm in an aqueous solution. The results ofin vitrocytotoxicity assays demonstrated that the P3H2 polymeric micelles significantly improved PDT efficacy on the SK-BR-3 cells due to the enhanced targeting ability. In addition, PDT treatment using the P3H2 polymeric micelles effectively killed breast cancer cells by inducing higher intracellular reactive oxygen species generation and apoptotic cell death. In particular, the three-dimensional cell culture model proved the synergistic PDT efficacy using P3H2 polymeric micelles on the SK-BR-3 cells. Based on these results, the PDT treatment using P3H2 polymeric micelles can serve as a highly effective therapeutic modality for breast cancer.

• Authors: Young-Jin Kim, Ji-Hui Ha, Ye-Ji Kim
• Journal: Nanotechnology (Nanotechnology) Vol. 32 Issue 27 (Apr 14 2021) ISSN: 1361-6528 [Electronic] England
• PMID: 33780921 (Publication Type: Journal Article)
• Copyright: © 2021 IOP Publishing Ltd.

Chemical References

• Micelles
• Photosensitizing Agents
• Chlorophyll
• Polylysine
• Polyethylene Glycols
• Hyaluronic Acid
• ERBB2 protein, human
• Receptor, ErbB-2
• pheophorbide a

Topics

• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chlorophyll (analogs & derivatives, chemistry, pharmacology, therapeutic use)
• Female
• Humans
• Hyaluronic Acid (chemistry)
• Micelles
• Photochemotherapy
• Photosensitizing Agents (chemistry, pharmacology, therapeutic use)
• Polyethylene Glycols (chemistry)
• Polylysine (chemistry)
• Receptor, ErbB-2 (metabolism)