Almost all currently used cytotoxic agents are associated with severe toxicities and other undesirable side effects. Therefore, the discovery of new and effective anticancer drugs is one of the greatest current challenges. One strategy to increase the cancer cell-selectivity and reduce drug’s systemic toxicity is to build the tumor-targeted drug delivery systems (TTDDSs). This approach has led to the development of highly efficacious drug conjugates, which recognize the intrinsic differences between normal and tumor cells and exhibit a few orders of magnitude higher selectivity to cancer cells as compared to normal cells.<br/>Herein, we present the design, synthesis and biological evaluation of novel tumor-targeting drug conjugates. Receptors for vitamins, e.g., vitamin B6 (biotin), B9 (folate) and B12 (cobalamin), are widely overexpressed on the surface of a variety of cancer cells. Therefore, biotin was selected as tumor-targeting module (TTM). Monensin A and thiocolchicine derivative were used as cytotoxic components of conjugates and were connected to biotin through a self-immolative disulfide linker with or without solubilizing spacer. This smart linker is readily cleaved through a cascade thiolactonization process, which is primarily triggered by endogenous thiols such as glutathione, to release the unmodified original drug. The antiproliferative activity of both TTDDSs and their payloads was evaluated against several cancer and normal cell lines.

Tumor-targeting drug conjugates of monensin A, colchicine or their derivatives

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.