GRP78-Targeted HPMA Copolymer-Photosensitizer Conjugate for Hyperthermia-Induced Enhanced Uptake and Cytotoxicity in MCF-7 Breast Cancer Cells.
Gantumur BattogtokhOyuntuya GotovNithya SubrahmanyamYoung Tag KoHamidreza GhandehariPublished in: Macromolecular bioscience (2019)
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.
Keyphrases
- photodynamic therapy
- breast cancer cells
- cancer therapy
- induced apoptosis
- endoplasmic reticulum stress
- fluorescence imaging
- heat shock
- drug delivery
- drug release
- cell cycle arrest
- cell surface
- heat stress
- type diabetes
- transcription factor
- binding protein
- pi k akt
- heat shock protein
- drug induced
- weight loss
- adipose tissue