Preparation of a Camptothecin‐conjugated Molecular Carrier and its Cytotoxic Effect Toward Human Colorectal Carcinoma In Vitro

Abstract

Camptothecin (CPT) and its derivatives are the only chemical class that targets the enzymatic activity of DNA topoisomerase I, which is involved in DNA damage and subsequent cell apoptosis. Despite CPT's advantages, its use has been restricted due to extremely poor solubility, drug resistance by several efflux pumps, short half‐life, and poor bioavailability. To overcome these limitations, we designed and synthesized a water‐soluble CPT‐conjugated molecular transporter that successfully and rapidly delivered CPT into cells. The conjugate had affinity toward mitochondria inside cells and it was distributed mainly to kidney, lung, and spleen. MTT assay confirmed that the CPP‐conjugate decreased cell viability of colon cancer cell lines to a much greater extent than the parent drug. This novel approach has the potential of improving CPT efficacy for future in vivo applications, especially for colon cancer therapy.

Mitochondria targeting molecular transporters: synthesis, lipophilic effect, and ionic complex

“…The molecular transporters were non-peptides, and they had carbohydrates as scaffolds to which multiple guanidines were attached via linkers. When drugs like paclitaxel, camptothecin, AZT, 5-Fu, and ibuprofen were covalently conjugated to the molecular transporters, the conjugates were well-internalized into the cells (Maiti et al., 2007 ; Im et al., 2011 ; Jeong et al., 2018 ). Some of the drug-conjugated molecular transporters demonstrated dominant cellular localization in mitochondria.…”

Quaternary ammonium‐based mitochondria targeting anticancer agents with high water solubility

“…Mitochondria are cellular organelles that are pivotal to intracellular activities and play roles in programmed cell death, generation of reactive oxygen species (ROS), and maintenance of ionic homeostasis. [1][2][3] Especially, mitochondria in cancer cells are characterized with a more negatively charged membrane than normal cells, suggesting that delocalized lipophilic cations accumulate into the mitochondria of cancer cells 10 times greater than those of the normal cells. [4][5][6][7] Additionally, delivering the conventional anticancer drug into mitochondria has been reported as an efficient approach to overcoming drug resistance.…”