1.Department of Chemistry,Tarbiat Modares University,Tehran,Iran;2.Department of Clinical Biochemistry, Faculty of Medical Sciences,Tarbiat Modares University,Tehran,Iran;3.Department of Chemistry and Biochemistry,University of California, Los Angeles,Los Angeles,USA;4.Department of Chemistry, Faculty of Science,Cairo University,Giza,Egypt;5.California NanoSystems Institute,University of California, Los Angeles,Los Angeles,USA
Abstract:
Biotemplated metal nanoclusters have garnered much attention owing to their wide range of potential applications in biosensing, bioimaging, catalysis, and nanomedicine. Here, we report the synthesis of stable, biocompatible, water-soluble, and highly fluorescent bovine serum albumin-templated cadmium nanoclusters (CdNCs) through a facile one-pot green method. We covalently conjugated hyaluronic acid (HA) to the CdNCs to form a pH-responsive, tumortargeting theranostic nanocarrier with a sustained release profile for doxorubicin (DOX), a model anticancer drug. The nanocarrier showed a DOX encapsulation efficiency of about 75.6%. DOX release profiles revealed that 74% of DOX was released at pH 5.3, while less than 26% of DOX was released at pH 7.4 within the same 24-h period. The nanocarrier selectively recognized MCF-7 breast cancer cells expressing CD44, a cell surface receptor for HA, whereas no such recognition was observed with HA receptor-negative HEK293 cells. Biocompatibility of the nanocarrier was evaluated through cytotoxicity assays with HEK293 and MCF-7 cells. The nanocarrier exhibited very low to no cytotoxicity, whereas the DOX-loaded nanocarrier showed considerable cellular uptake and enhanced MCF-7 breast cancer cell-killing ability. We also confirmed the feasibility of using the highly fluorescent nanoconjugate for bioimaging of MCF-7 and HeLa cells. The superior targeted drug delivery efficacy, cellular imaging capability, and low cytotoxicity position this nanoconjugate as an exciting new nanoplatform with promising biomedical applications.
