title: Green design "bioinspired disassembly-reassembly strategy" applied for improved tumor-targeted anticancer drug delivery.
abstract: In this study, a simple and green approach 'bioinspired disassembly-reassembly strategy' was employed to reconstitute lipoprotein nanoparticles (RLNs) using whole-components of endogenous ones (contained dehydrated human lipids and native apolipoproteins). These RLNs were engineered to mimic the configuration and properties of natural lipoproteins for efficient drug delivery. In testing therapeutic targeting to microtubules, paclitaxel (PTX) was reassembled into RLNs to achieve improved targeted anti-carcinoma treatment and minimize adverse effects, demonstrating ultimately more applicable than HDL-like particles which are based on exogenous lipid sources. We have characterized that apolipoprotein-decoration of PTX-loaded RLNs (RLNs-PTX) led to favoring uniformly dispersed distribution, increasing PTX-encapsulation with a sustained-release pattern, while enhancing biostability during blood circulation. The innate biological RLNs induced efficient intracellular trafficking of cargos in situ via multi-targeting mechanisms, including scavenger receptor class B type I (SR-BI)-mediated direct transmembrane delivery, as well as other lipoprotein-receptors associated endocytic pathways. The resulting anticancer treatment from RLNs-PTX was demonstrated a half-maximal inhibitory concentration of 0.20μg/mL, cell apoptosis of 18.04% 24h post-incubation mainly arresting G2/M cell cycle in vitro, and tumor weight inhibition of 70.51% in vivo. Collectively, green-step assembly-based RLNs provided an efficient strategy for mediating tumor-targeted accumulation of PTX and enhanced anticancer efficacy.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Ruoning
authors.initials: R
authors.lastname: Wang
authors.affiliation: College of Pharmacy, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB R3E 0T5, Canada.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: zhoujianp60@163.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
authors.affiliation: National Engineering and Research Center for Target Drugs, Jiangsu, Hengrui Medicine CO., LTD, 7 Kunlun Shan Road, Lianyungang 222000, China.
authors.forename: Lingjia
authors.initials: L
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Peiying
authors.initials: P
authors.lastname: Hua
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: dydszyzf@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D055772:Green Chemistry Technology; D006461:Hemolysis / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008055:Lipids; D017239:Paclitaxel
keywords: Bioinspired disassembly-reassembly strategy; Enhanced anticancer efficacy; Green designed lipoprotein-like nanoparticles; Multi-targeting system; Safety profile