Molecular switch for the assembly of lipophilic drug incorporated plasma protein nanoparticles and in vivo image.
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.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Guangming
G
Gong
Yan
Y
Xu
Yuanyuan
Y
Zhou
Zhengjie
Z
Meng
Guoyan
G
Ren
Yang
Y
Zhao
Xiang
X
Zhang
Jinhui
J
Wu
Yiqiao
Y
Hu
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D002942:Circular Dichroism; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D010316:Particle Size; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D041622:Tomography, Optical / Q000379:methods*
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D012709:Serum Albumin; D017239:Paclitaxel