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

Abstract

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.

Protective Effect of Rifampicin Loaded by HPMA-PLA Nanopolymer on Macrophages Infected with Mycobacterium Tuberculosis

“…N-(2-Hydroxypropyl) methacrylamide (HPMA) is a hydrophilic copolymer, which can improve the solubility of hydrophobic drugs in water. In view of its ability to prepare nanopolymer micelles, we also choose it as a hydrophilic carrier [ 9 ]. The main advantages of copolymer micelles are that they are readily bound by a variety of chemical species and are an important and attractive class of drug carriers for intravenous administration of hydrophobic drugs [ 10 ].…”

Synthesis and Preclinical Evaluation of [68Ga]SP94 for Micro-PET Imaging of GRP78 Expression in Hepatocellular Carcinoma

“…Detection of GRP78 expression using PET imaging has key advantages, including (1) the ability to obtain noninvasive total-body imaging procedure; (2) the procedure is operator-independent and can easily be repeated; (3) allowing a more accurate quantitative assessment of the total amount of GRP78 expression in an individual patient. Although several receptor-targeted delivery platforms have so far been reported, such as HSP peptide (WDLAW­MFRLPVG), VAP peptide (SNTRVAP), and anti-KDEL antibodies, none of these have reaped significant benefits in clinical trials until now. In 2019, Jiang et al identified that GRP78 was the membrane receptor of HCC-targeted peptide sequence GGGSFS­IIHTPILPL (SP94 for short) using immunoprecipitation and mass spectrum analysis .…”