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 of in vitro cytotoxicity 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.

Cell Membrane-Coated Halloysite Nanotubes for Target-Specific Nanocarrier for Cancer Phototherapy

“…Compared with traditional chemical drugs, nanomedicines have many advantages such as improved in vivo bioavailability, favorable targeting and controllable drug release ability. So far, a variety of organic nanoparticles have shown their highly efficiency in the treatment of breast cancer with low toxicity [ 9 ], including liposomes [ 10 , 11 ], polymer micelles [ 12 , 13 ] and dendrimers [ 14 , 15 ]. In addition, inorganic nanoparticles have attracted considerable attention due to their nanoscale size, good stability and ease of synthesis and modification [ 16 ].…”

HER2-Specific Peptide (LTVSPWY) and Antibody (Herceptin) Targeted Core Cross-Linked Micelles for Breast Cancer: A Comparative Study

“…Conjugation of the hydrophobic peptide to the nanoparticles might cause solubility problems due to its amino acid content. PEG-coupling to the LTVSPWY peptide has been applied to overcome this problem, resulting in better aqueous solubility characteristics [ 36 , 51 , 52 ]. In our case, instead of using PEG-coupling to LTVSPWY, we directly conjugated LTVSPWY peptides towards the carboxylic group into the polysufobetaine shell part of the micelles.…”

Advances in active targeting of ligand-directed polymeric nanomicelles via exploiting overexpressed cellular receptors for precise nanomedicine

“…Kim and his colleagues developed targeted self-assembled PMs for enhancing photodynamic therapy (PDT) against HER-2 positive breast cancer cells. 23 The PMs consist of pheophorbide a (Pheo a), functionalized methoxy poly[ethylene glycol], block, poly[ l -lysine hydrochloride] [PEG-PLL] to form [PEG-PLL-Pheo a] via amide bond formation using DCC conjugation reaction. The HER2 targeting peptide (HLTV) was conjugated to hyaluronic acid (HA) through EDC conjugation procedure to form (HLTV-HA).…”