GRP78‐Targeted HPMA Copolymer‐Photosensitizer Conjugate for Hyperthermia‐Induced Enhanced Uptake and Cytotoxicity in MCF‐7 Breast Cancer Cells

• Published in: Macromolecular bioscience Vol. 19; no. 7; pp. e1900032 - n/a
• Main Authors: Battogtokh, Gantumur, Gotov, Oyuntuya, Subrahmanyam, Nithya, Ko, Young Tag, Ghandehari, Hamidreza
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.07.2019
• Subjects: 2‐[1‐hexyloxyethyl]‐2‐divinyl pyropheophorbide‐a (HPPH), heat shock protein, hyperthermia; Breast cancer; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cell Death - drug effects; Conjugates; Copolymers; Cytotoxicity; Endocytosis; Female; Fever; Heat shock; Heat shock proteins; Heat-Shock Proteins - metabolism; Humans; Hyperthermia; Hyperthermia, Induced; MCF-7 Cells; Methacrylamide; Methacrylates - chemical synthesis; Methacrylates - chemistry; N‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymers, photodynamic therapy; Photodynamic therapy; Photosensitizing Agents - pharmacology; Polymers - chemical synthesis; Polymers - chemistry; Receptors; Selectivity; Solubility; Toxicity; Tumors; 2-[1-hexyloxyethyl]-2-divinyl pyropheophorbide-a (HPPH), heat shock protein, hyperthermia; N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, photodynamic therapy
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201900032

Photodynamic therapy (PDT) is a promising cancer treatment approach. However, the photosensitizers (PS) used for PDT are often limited by their poor solubility and selectivity for tumors. The goal of this study is to improve water solubility and delivery of the photosensitizer 2‐[1‐hexyloxyethyl]‐2‐divinyl pyropheophorbide‐a (HPPH) to breast cancer cells. An N‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymer–HPPH photosensitizer conjugate is synthesized with heat shock receptor glucose‐regulated protein 78 (GRP78), targeting to GRP78 receptors of MCF‐7 cells, which are upregulated under mild hyperthermia. It is found that the uptake of the GRP78 targeted pep‐HPMA‐HPPH copolymer conjugate in MCF‐7 cells is improved through heat induction. Under mild hyperthermia the targeted copolymers are more effective compared to free HPPH. These results show potential for the utility of mild hyperthermia and copolymer delivery vehicles to enhance the efficacy of photodynamic therapy. In this work, HPMA‐copolymer is synthesized to be used as a carrier system of hydrophobic photosensitizer. Then, to the HPMA‐copolymer a photosensitizer is attached, HPPH, and heat shock protein targeting peptide to improve cancer cell targeting ability of the photosensitizer. The conjugate shows high uptake and strong phototoxicity in cancer cell in the presence of mild hyperthermia.