Liu, Ying Steiniger, Sebastian C. J. Kim, YoungSoo Kaufmann, Gunnar F. Felding-Habermann, Brunhilde Janda, Kim D. 2024-01-21T01:03:56Z 2024-01-21T01:03:56Z 2021-08-31 2007-05 1543-8384 https://pubs.kist.re.kr/handle/201004/134437 Major obstacles in the development of new therapeutic anticancer drugs are the low bioavailability of hydrophilic substances and the nonspecific toxicity toward healthy tissues. As such, cell-targeting oligopeptides have emerged as attractive drug delivery vehicles for a variety of different types of cargo. The recently identified peptide Pep42 binds to the glucose-regulated protein 78 (GRP78), which is overexpressed on the cell surface of human cancer cells and internalizes into these cells. Herein, we demonstrate how Pep42 can be utilized as a carrier for different types of cytotoxic drugs to specifically target human cancer cell lines in vitro in a strictly GRP78-dependent manner. Furthermore, the mechanism of internalization of Pep42 was elucidated and found to involve clathrin-mediated endocytosis. Pep42 subsequently colocalizes within the lysosomal compartment. Importantly, we also provide evidence that Pep42-conjugated quantum dots have the ability to selectively enrich in tumor tissue in a xenograft mouse model. Our results suggest that the highly specific GRP78-Pep42 interaction can be utilized for the generation of Pep42-drug conjugates as a powerful anticancer drug delivery system that could substantially enhance the efficacy of chemotherapy by increasing the drug-tumor specificity, thus minimizing the adverse side effects associated with conventional cancer therapeutics. English AMER CHEMICAL SOC PENETRATING PEPTIDES ENDOPLASMIC-RETICULUM CHAPERONE GRP78 LUNG-CANCER PROTEINS BINDING EXPRESSION SELECTION INTERNALIZATION ACTIVATION Mechanistic studies of a peptidic GRP78 ligand for cancer cell-specific drug delivery Article 10.1021/mp060122j 1 MOLECULAR PHARMACEUTICS, v.4, no.3, pp.435 - 447 MOLECULAR PHARMACEUTICS 4 3 435 447 scie scopus 000246908000014 Medicine, Research & Experimental Pharmacology & Pharmacy Research & Experimental Medicine Pharmacology & Pharmacy Article PENETRATING PEPTIDES ENDOPLASMIC-RETICULUM CHAPERONE GRP78 LUNG-CANCER PROTEINS BINDING EXPRESSION SELECTION INTERNALIZATION ACTIVATION drug delivery tumor targeting GRP78 heat shock protein cyclic peptide