title: Novel self-assembly endows human serum albumin nanoparticles with an enhanced antitumor efficacy.
abstract: Protein-based nanomedicine plays an important role in tumor chemotherapy due to their merits in bioavailability, biocompatibility, biodegradability, and low toxicity. In this study, we developed a novel method of preparing human serum albumin (HSA) nanoparticles for targeted delivery of paclitaxel (PTX) to tumors. HSA-PTX nanoparticles (NPs-PTX) were fabricated via unfolding of HSA in appropriate solution to expose more hydrophobic domains and consequent self-assembling into nanoparticles with added PTX. Via this self-assembly method, a desirable particle size (around 120 nm), a high drug loading (>20%), and a high encapsulation efficiency (near 100%) were obtained. PTX dispersed as an amorphous state in NPs-PTX and the secondary structures of HSA were maintained. In a cytotoxicity study, NPs-PTX displayed an enhanced cytotoxicity in MCF-7 and A549 cells. Confocal microscopy and flow cytometry revealed that the uptake of NPs-PTX was mediated by secreted protein acidic and rich in cysteine and "caveolar" transport. In H22 tumor-bearing mice, NPs-PTX displayed an increasing and everlasting tumor distribution, leading to slower tumor growth and longer mice survival than PTX. Therefore, this novel self-assembly method offers a much easier method to prepare PTX nanoparticles, provides better antitumor efficacy in vitro and in vivo, and more importantly, sets up a delivery platform for other hydrophobic drugs to improve their effectiveness in cancer therapy.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, People's Republic China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Ding
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Tang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Cao
authors.forename: Jinhui
authors.initials: J
authors.lastname: Wu
authors.forename: Ahu
authors.initials: A
authors.lastname: Yuan
authors.forename: Qian
authors.initials: Q
authors.lastname: Qiao
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry* / Q000494:pharmacology*; D010316:Particle Size; D012709:Serum Albumin / Q000737:chemistry* / Q000494:pharmacology*; D012996:Solutions / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012709:Serum Albumin; D012996:Solutions; D017239:Paclitaxel