Antibody-drug conjugates (ADCs) represent a novel class of anticancer agents with a promising therapeutic approach for cancer chemotherapy. An antibody-drug conjugate (ADC) combines three structural units; antibody, linker, and the cytotoxic payload. Hence, the design of an ADC is a complex process; the success of these entities depends on a specific selection of each component, including the specificity antibody to target a particular cell, improving the properties of the linker, and the cytotoxic potency of chemotherapeutic.1,2 In the past decade, substantial progress has been made in the area of antibody-drug conjugates (ADCs) for the possible applications in both imagining and therapeutic applications but examples of metal-based ADCs are still scarce.3 Our research group reported in 2019 on ADCs based on AuPPh3 as cytotoxic payload and the HER2-positive monoclonal antibody trastuzumab, which showed potent cytotoxicity and selectivity towards HER2-positive breast cancer cell lines.4 We report here on the synthesis of second generation gold(I)-containing linkers amenable to bioconjugation to monoclonal antibodies, which include phosphanes and N-heterocyclic carbenes as ligands. In addition, we report on a gold(I)-containing linker that incorporates a fluorescent BODIPY phosphane moiety with potential utility for simultaneous targeted therapy and molecular imaging. The bioconjugation of these gold-linkers to trastuzumab will be described along with their preliminary biological evaluation. Internalization studies with the fluorescent derivative will also be described in order to ascertain the potential mode of action of these ACDs.

Developing antibody-gold based drug conjugates for targeted delivery and molecular imaging for HER-2 positive cancers

ACS Spring Meeting 2021

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