title: Layer-by-layer assembly of hierarchical nanoarchitectures to enhance the systemic performance of nanoparticle albumin-bound paclitaxel.
abstract: Although protein-bound paclitaxel (PTX, Abraxane®) has been established as a standard PTX-based therapy against multiple cancers, its clinical success is limited by unfavorable pharmacokinetics, suboptimal biodistribution, and acute toxicities. In the present study, we aimed to apply the principles of a layer-by-layer (LbL) technique to improve the poor colloidal stability and pharmacokinetic pattern of nanoparticle albumin-bound paclitaxel (nab-PTX). LbL-based nab-PTX was successfully fabricated by the alternate deposition of polyarginine (pARG) and poly(ethylene glycol)-block-poly (L-aspartic acid) (PEG-b-PLD) onto an albumin conjugate. The presence of protective entanglement by polyamino acids prevented the dissociation of nab-PTX and improved its colloidal stability even at a 100-fold dilution. The combined effect of high nanoparticle internalization and controlled release of PTX from LbL-nab-PTX increased its cytotoxicity in MCF-7 and MDA-MB-231 breast cancer cells. LbL-nab-PTX consistently induced apoptosis in approximately 52% and 22% of MCF-7 and MDA-MB-231 cancer cells, respectively. LbL assembly of polypeptides effectively prevented exposure of PTX to the systemic environment and thereby inhibited drug-induced hemolysis. Most importantly, LbL assembly of polypeptides to nab-PTX effectively increased the blood circulation potential of PTX and improved therapeutic efficacy via a significantly higher area under the curve (AUC)0-∞. We report for the first time the application of LbL functional architectures for improving the systemic performance of nab-PTX with a view toward its clinical translation for cancer therapy.
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan 712-749, South Korea.
authors.forename: Hima Bindu
authors.initials: HB
authors.lastname: Ruttala
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan 712-749, South Korea.
authors.forename: Thiruganesh
authors.initials: T
authors.lastname: Ramasamy
authors.affiliation: College of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup, Gyeongsan, 712-702, South Korea.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.affiliation: College of Pharmacy, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan 712-749, South Korea. Electronic address: csyong@yu.ac.kr.
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan 712-749, South Korea. Electronic address: jongohkim@yu.ac.kr.
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
mesh_terms: D000068196:Albumin-Bound Paclitaxel / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000068196:Albumin-Bound Paclitaxel; D001224:Aspartic Acid; D011092:Polyethylene Glycols
keywords: Albumin; Breast cancer; Colloidal stability; Nanoparticle; Systemic performance