Molecular Switch For the Assembly of Lipophilic Drug Incorporated Plasma Protein Nanoparticles and In Vivo image

Abstract

A strategy to manipulate the disulfide bond breaking triggered unfolding, and subsequently assembly of human serum albumin (HSA) in a lipophilic drug-dependent manner is present. In this study, the hydrophobic region, a molecular switch of the HSA, was regulated to form HSA-paclitaxel (HSA-PTX) nanoparticles by a facile route. High-resolution transmission electron microscopy and fluorescence quenching indicate that HSA coassembled with PTX, which acts as a bridge to form core-shell nanoparticles about 50-240 nm in size, and that PTX might bind to the subdomain IIA sites of HSA. Change of ultraviolet absorption and circular dichroism spectra reveal the formation of HSA-PTX nanoparticles, which is a safety, injectable pharmaceutic nanocarrier system for tumor target. This method to prepare nanocarrier systems for hydrophobic guest molecules reveals a general principle of self-assembly for other plasma proteins and other pharmacologically active substances with poor water solubility. It also provides a basis for developing nanocarrier systems for a wide range of applications in nanomedicine, from drug delivery to bioimaging systems.

Enhanced tolerance and antitumor efficacy by docetaxel-loaded albumin nanoparticles

“…In our previous work, we successfully developed a novel strategy to prepare drug-loaded albumin nanoparticles (Gong et al, 2011(Gong et al, , 2012Hu et al, 2011). This method is based on the hydrophobic interactions between drugs and internal regions of protein.…”

“…To overcome above-mentioned barriers, we had successfully pioneered a novel simple strategy to fabricate drugloaded albumin nanoparticle in our previous work (Gong et al, 2011;Hu et al, 2011;Gong et al, 2012). In this strategy, albumin was unfolded to expose hydrophobic regions and interacted with hydrophobic drugs to form nanoparticles.…”

Long-circulating self-assembled cholesteryl albumin nanoparticles enhance tumor accumulation of hydrophobic anticancer drug

“…Tubes were immersed in 3 mL of PBS (pH 7.4) containing 0.5% (w/v) Tween 80 and incubated at 37°C with rotation at 50 rpm. All the dissolution medium (3 mL) was collected at various time points (1,2,3,4,6,9,12,24,48, and 72 h), and replaced by 3 mL fresh medium at 37°C. The amounts of PTX released were assessed by HPLC analysis.…”

“…BSA is widely used for drug delivery because of its medical importance, abundance, low cost, ease of purification, and unusual ligand-binding properties [12]. Albumin-based nanoparticle carrier systems represent an attractive strategy, because a significant amount of drug can be incorporated into the particle matrix, owing to the different drug binding sites present in the albumin molecule [13] as well as its biocompatibility.…”

Design, Development and Evaluation of Erlotinib-Loaded Hybrid Nanoparticles for Targeted Drug Delivery to NonSmall Cell Lung Cancer

“…It has a single polypeptide chain consisting of about 583 amino acids residues, 17 intrachain disulfide bridges, and 1 sulfhydryl group (243). BSA based albumin NPs (ANPs) are produced by desolvation or coacervation (244)(245)(246)(247)(248), emulsification (249,250), thermal gelation (251,252), nanospray drying (253), nabtechnology (254), disulfide bond reduction (255,256), and self-assembly methods (257). Desolvation is the most widely used method for the preparation of ANPs.…”