title: Polypeptide-based "smart" micelles for dual-drug delivery: a combination study of experiments and simulations.
abstract: A dual-drug-loaded micelle is designed and constructed from a mixture of poly(propylene oxide)-b-poly(γ-benzyl-l-glutamate)-b-poly(ethylene glycol) (PPO-b-PBLG-b-PEG) triblock terpolymers and two model drugs, doxorubicin (DOX) and naproxen (Nap). In the micelles, the DOX is chemically linked to the PBLG backbones through an acid-cleavable hydrazone bond, whereas the Nap is physically encapsulated in the cores. The drug loading and releasing behaviors of the dual-drug-loaded micelles as well as single drug-loaded micelles (DOX-conjugated or Nap-loaded micelles) are studied. The structures of micelles are characterized by means of microscopies and dynamic light scattering, and further examined by dissipative particle dynamics (DPD) simulations. It is revealed that the micelles possess a core-shell-corona structure in which the PPO/Nap, PBLG/DOX, and PEG aggregate to form the core, shell, and corona, respectively. In vitro studies reveal that the release of DOX and Nap is pH- and thermosensitive. Such drug releasing behaviors are also examined by DPD simulations, and more information regarding the mechanism is obtained. In addition, the bio-related properties such as cellular uptake of the micelles and biocompatibility of the deliveries are evaluated. The results show that the dual-drug-loaded micelles are biocompatible at normal physiological conditions and retain the anti-cancer efficiency.
authors.affiliation: Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Cai
authors.forename: Liquan
authors.initials: L
authors.lastname: Wang
authors.forename: Jiaping
authors.initials: J
authors.lastname: Lin
authors.forename: Xuguang
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008823:Micelles; D009288:Naproxen / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D011409:Propylene Glycols; C012504:polypropylene glycol; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D009288:Naproxen; D004317:Doxorubicin
keywords: DPD simulation; drug delivery; micelles; polypeptides