A Dual Bioconjugated Virus-Like Nanoparticle as a Drug Delivery System and Comparison with a pH-Responsive Delivery System

Abstract

Modifications of virus-like nanoparticles (VLNPs) using chemical conjugation techniques have brought the field of virology closer to nanotechnology. The huge surface area to volume ratio of VLNPs permits multiple copies of a targeting ligand and drugs to be attached per nanoparticle. By exploring the chemistry of truncated hepatitis B core antigen (tHBcAg) VLNPs, doxorubicin (DOX) was coupled covalently to the external surface of these nanoparticles via carboxylate groups. About 1600 DOX molecules were conjugated on each tHBcAg VLNP. Then, folic acid (FA) was conjugated to lysine residues of tHBcAg VLNPs to target the nanoparticles to cancer cells over-expressing folic acid receptor (FR). The result demonstrated that the dual bioconjugated tHBcAg VLNPs increased the accumulation and uptake of DOX in the human cervical and colorectal cancer cell lines compared with free DOX, resulting in enhanced cytotoxicity of DOX towards these cells. The fabrication of these dual bioconjugated nanoparticles is simple, and drugs can be easily conjugated with a high coupling efficacy to the VLNPs without any limitation with respect to the cargo’s size or charge, as compared with the pH-responsive system based on tHBcAg VLNPs. These dual bioconjugated nanoparticles also have the potential to be modified for other combinatorial drug deliveries.

Targeted delivery of 5-fluorouracil-1-acetic acid (5-FA) to cancer cells overexpressing epithelial growth factor receptor (EGFR) using virus-like nanoparticles

“…The tHBcAg VLNP is highly stable and robust, and it possesses a large surface area containing a variety of amino acid residues with different functional groups 28 , 33 . Hence, various targeting ligands can be displayed easily on the surface of tHBcAg VLNPs to attain targeted drug delivery for cancer therapeutics 11 , 13 , 30 , 34 , 35 .…”

“…Hepatitis B VLNP comprising 180 or 240 subunits of the viral core antigen (HBcAg) has been studied intensively in the development of multicomponent vaccines and drug delivery systems [28][29][30] . A truncated HBcAg (tHBcAg), a mutant without the C-terminal arginine rich domain, also self-assembles into icosahedral VLNP [31][32][33] .…”

Thermally-responsive Virus-like Particle for Targeted Delivery of Cancer Drug

“…Many types of cancer cells including ovary, uterus, kidney, colon, brain and lung cancers over express folic acid receptor (FR) which binds specifically to folic acid (FA) with a high affinity 31,32 . Therefore, FA has been conjugated to many drug delivery nanocarriers to specifically target cancer cells 12–14,33,34 . In this study, we established a Dox delivery system using a novel thermally-responsive nanocarrier based on MrNVLP.…”

Biodegradable Micelles for NIR/GSH-Triggered Chemophototherapy of Cancer

“…In addition, chemotherapy based on stimuli-responsive drug delivery systems (SDDSs) have been implemented in extensive research and have been combined with phototherapy [7,8,9,10,11]. Various sensitive functional groups (e.g., disulfide, hydrazide, and imidazole) have been widely introduced into SDDSs to achieve controllable drug release and cancer therapy [12,13,14,15,16]. Among them, the reductive glutathione (GSH), with a discrepant concentration gradient between the extracellular fluid (2–10 μM) and the tumor intracellular fluid (2–10 mM), can allow SDDSs to quickly release their payload through the cleavage of disulfide bonds to achieve chemotherapy [17,18,19].…”