Design,in silicomodelling and functionality theory of folate-receptor-targeted myricetin-loaded bovine serum albumin nanoparticle formulation for cancer treatment

Abstract

Targeted drug delivery systems are a promising field of research. Nano-engineered material-mediated drug delivery possesses remarkable potential for the treatment of various malignancies. Here, folic acid (FA)-conjugated bovine serum albumin (BSA) nanoparticles (NPs) were used to encapsulate myricetin (Myr). Subsequently, the delivery of Myr via naturally overexpressed folate receptor (FR) to FR-positive breast cancer cells was studied. Myr-loaded BSA NPs were assembled by modified desolvation cross-linking technique. An FA-conjugated carrier, N-hydroxysuccinimide (NHS)-FA ester, was successfully synthesized. Its functional and structural characteristics were confirmed by ultraviolet, Fourier-transform infrared, and proton nuclear magnetic resonance spectroscopy. Biocompatible FA-conjugated, Myr-loaded BSA NPs (FA-Myr-BSA NPs) were successfully formulated using a carbonate/bicarbonate buffer. Their morphology, size, shape, physiological stability, and drug release kinetics were studied. Molecular docking studies revealed that FA-Myr-BSA NPs readily bound non-covalently to folate receptors and facilitated active drug endocytosis. FA-Myr-BSA NPs could trigger fast release of Myr in an acidic medium (pH 5.4), and showed high biocompatibility in a physiological medium. FA-Myr-BSA NPs effectively decreased the viability of MCF-7 cells after 24 h with 72.45 μg ml−1 IC50 value. In addition, FA-Myr-BSA NPs enhanced the uptake of Myr in MCF-7 cells. After incubation, a typical apoptotic morphology of condensed nuclei and distorted membrane bodies was observed. The NPs also targeted mitochondria of MCF-7 cells, significantly increasing reactive oxygen species release and contributing to the loss of mitochondrial membrane integrity. The observed results confirm that the newly developed FA-Myr-BSA NPs can serve as a potential carrier for Myr to increase the anticancer activity of this chemotherapeutic.

Mixed phytochemicals mediated synthesis of copper nanoparticles for anticancer and larvicidal applications

“…The cytotoxic potential of Wt-CuNPs performed against (MCF-7) human breast cancer and normal (Vero) cell lines by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) based rapid colorimetric assay [31]. For screening, the MCF-7 cells were seeded in a 96-well plate in 100 μL of medium containing 5% FBS, at plating density 10,000 cells/well and incubated at 37 ͦ C, 5% CO 2 , 95% air and relative humidity (100%) for 48 h prior to addition of Wt-Cu NPs.…”

ROS-Mediated Apoptosis Induced by BSA Nanospheres Encapsulated with Fruit Extract of Cucumis prophetarum in Various Human Cancer Cell Lines

“…In the cancerous cells, the ROS plays an important role in the proapoptotic effect, and change in the ROS level can cause respiratory change interruption, which may lead to the p53-mediated intrinsic apoptosis pathway. 35 In general, the alteration of the intracellular ROS level by anticancerous agents leads to an imbalance in the homeostatic redox state, induction of genotoxicity, and, finally, induction of programmed cell death. 36 Change in the intracellular ROS level may be considered a promising anticancer mode of action for Cp-BSA nanospheres.…”

Surface receptor‐mediated targeted drug delivery systems for enhanced cancer treatment: A state‐of‐the‐art review

“…The targeted therapeutics was developed upon the selective binding abilities between ligands and corresponding receptors that are overexpressed on pathologic cell surface (Kunjiappan et al, 2020). The nano‐engineered vehicle/nanoparticle can be specially intended through minor modifications like simple chemistry to attach ligands on the surface of nanocarriers, size, shape, maximum encapsulation of a variety of drugs, physicochemical characteristics and so on, which will deliver the drugs to the desired pathologic cells.…”

“…Further, receptor targeting strategy can be achieved by specialized drug carriers (cargo) such as metal particles (Kunjiappan et al, 2015; Zhang et al, 2010), liposomes (Wu et al, 2006), hydrogels (Mohammadi et al, 2016), polymers (Kim et al, 2008; Yoo & Park, 2004a), dendrimers (Quintana et al, 2002; Shukla et al, 2003), carbon nanotubes (Castillo et al, 2013; Lu et al, 2012), protein‐drug conjugates (Kim et al, 2005; Matulic‐Adamic et al, 2002), polysaccharides (Bae & Na, 2010), and peptides (Futaki et al, 2007). The drug incorporated carrier is associated with the receptor and allows the entry of large quantities of unmodified drugs to the cancer cells (Kunjiappan et al, 2020). Figure 2 displays a general overview of the cell surface receptor‐mediated targeted drug delivery system via a small linker (breakable) covalently conjugated with the delivery carrier.…”