Fabrication of doxorubicin loaded aptamer-functionalized cationic β-lactoglobulin nanocomplex: A biocompatible multifunctional nanoplatform for encapsulation and controlled release of anticancer drugs

Abstract

Owing to elegant biomacromolecule features, proteins have been investigated to prepare a multifunctional and targeted nanoscale drug delivery systems. In this work, a novel cationic protein based nanocarrier, AS1411 aptamer-conjugated poly-L-lysine/β-lactogolubolin nanoparticles (BNP/PLL/Apt), was fabricated. The as-prepared nanocarrier offers an innovative formulation that combines the outstanding properties of protein nanocarriers and aptamer as a targeting agent for chemotherapy. To demonstrate the therapeutic potential of BNP/PLL/Apt, the nanocarriers were loaded with doxorubicin (DOX). The DOX-loaded BNP/PLL/Apt (BNP@DOX/PLL/Apt) exhibited high drug encapsulation efficiency, as high as 92%, and the controlled drug release profile in a mildly acidic physiological condition that could enhance therapeutic efficiency in cancerous cells. The in vitro assays of BNP@DOX/PLL/Apt illustrated that the synthesized drug delivery system was hemocompatible based on hemagglutination, coagulation and complement activation assay results. Besides, BNP@DOX/PLL/Apt was more potent against MCF-7 tumor cells than the free DOX. Thanks to the particular recognition between AS1411 aptamer and its receptor over-expressed on cancer cells, the BNP/PLL/Apt NPs show the enhanced cellular uptake in MCF-7 cells compared with the BNPs without aptameric modification. Moreover, the computational studies exhibited the reasonable binding affinity of β-lactogolubolin to DOX and activity of AS1411 aptamer against cancer cells which confirmed the experimental results. Overall, the resultants of this research possessed numerous advantages of BNP@DOX/PLL/Apt over free chemotherapy drugs and confirmed its great potential to address the clinical challenges observed in targeted anticancer drug delivery system. © 2023 Elsevier B.V.