Hyaluronic acid-engineered Bcl-2 inhibitor nanocrystals for site-specific delivery to breast tumor cells.

This investigation aims to repurpose venetoclax using hyaluronic acid-coated venetoclax nanocrystals (HA-VEN-NCs) to target breast cancer. An antisolvent precipitation method was used to fabricate the nanocrystals and optimize them using central composite design. Hyaluronic acid (HA)-coated and -uncoated nanocrystals were compared in terms of drug release, cell line studies, CD44-expressing breast tumor cell binding capability and anticancer activity. HA-VEN-NCs and venetoclax nanocrystals (VEN-NCs) showed pH-responsive drug-release behavior, exhibiting sustained release at pH 6.8. Our extensive cell line investigation showed that HA-VEN-NCs efficiently bind to CD44-expressing breast tumor cells and possess excellent anticancer activity (IC: 2.00 μg/ml) compared with VEN-NCs. Our findings anticipate that HA-VEN-NCs could serve as valuable nanoplatforms for cancer treatments in the future.