4.5 Article

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

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DOI: 10.1016/j.jddst.2023.104254

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?-lactogolubolin; Doxorubicin; Aptamer

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Proteins have been utilized to create a targeted nanoscale drug delivery system. A novel cationic protein based nanocarrier, AS1411 aptamer-conjugated poly-L-lysine/beta-lactogolubolin nanoparticles (BNP/PLL/Apt), was developed, which combined the advantages of protein nanocarriers and aptamer as a targeting agent. The loaded nanocarrier demonstrated high drug encapsulation efficiency and controlled drug release profile, resulting in enhanced therapeutic efficiency in cancerous cells.
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/beta-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 beta-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.

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