Single Domain Antibodies as Carriers for Intracellular Drug Delivery: A Proof of Principle Study.

ABSTRACT: Antibody-drug conjugates (ADCs) are currently used for the targeted delivery of drugs to diseased cells, but intracellular drug delivery and therefore efficacy may be suboptimal because of the large size, slow internalization and ineffective intracellular trafficking of the antibody. Using a phage display method selecting internalizing phages only, we developed internalizing single domain antibodies (sdAbs) with high binding affinity to rat PDGFRβ, a receptor involved in different types of diseases. We demonstrate that these constructs have different characteristics with respect to internalization rates but all traffic to lysosomes. To compare their efficacy in targeted drug delivery, we conjugated the sdAbs to a cytotoxic drug. The conjugates showed improved cytotoxicity correlating to th

SUBMITTER: Pronk SD 

PROVIDER: S-EPMC8301836 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature