title: Tailor-Made Temperature-Sensitive Micelle for Targeted and On-Demand Release of Anticancer Drugs.
abstract: The design of nanomedicines from the tuned architecture polymer is a leading object of immense research in recent years. Here, smart thermoresponsive micelles were prepared from novel architecture four-arm star block copolymers, namely, pentaerythritol polycaprolactone-b-poly(N-isopropylacrylamide) and pentaerythritol polycaprolactone-b-poly(N-vinylcaprolactam). The polymers were synthesized and tagged with folic acid (FA) to render them as efficient cancer cell targeting cargos. FA-conjugated block copolymers were self-assembled to a nearly spherical (ranging from 15 to 170 nm) polymeric micelle (FA-PM) with a sufficiently lower range of critical micelle concentration (0.59 × 10(-2) to 1.52 × 10(-2) mg/mL) suitable for performing as an efficient drug carrier. The blocks show lower critical solution temperature (LCST) ranging from 30 to 39 °C with high DOX-loading content (24.3%, w/w) as compared to that reported for a linear polymer in the contemporary literature. The temperature-induced reduction in size (57%) of the FA-PM enables a high rate of DOX release (78.57% after 24 h) at a temperature above LCST. The DOX release rate has also been tuned by on-demand administration of temperature. The in vitro biocompatibilities of the blank and DOX-loaded FA-PMs have been studied by the MTT assay. The cellular uptake study proves selective internalization of the FA-PM into cancerous cells (C6 glioma) compared that into normal cells (HaCaT). In vivo administration of the DOX-loaded FA-PMs into the C6 glioma rat tumor model resulted in significant accumulation in tumor sites, which drastically inhibited the tumor volume by ∼83.9% with respect to control without any significant systemic toxicity.
authors.affiliation: Rubber Technology Centre, ‡School of Medical Science and Technology, and §Department of Biotechnology, Indian Institute of Technology , Kharagpur 721302, India.
authors.forename: S
authors.initials: S
authors.lastname: Panja
authors.affiliation: Rubber Technology Centre, ‡School of Medical Science and Technology, and §Department of Biotechnology, Indian Institute of Technology , Kharagpur 721302, India.
authors.forename: G
authors.initials: G
authors.lastname: Dey
authors.affiliation: Rubber Technology Centre, ‡School of Medical Science and Technology, and §Department of Biotechnology, Indian Institute of Technology , Kharagpur 721302, India.
authors.forename: R
authors.initials: R
authors.lastname: Bharti
authors.affiliation: Rubber Technology Centre, ‡School of Medical Science and Technology, and §Department of Biotechnology, Indian Institute of Technology , Kharagpur 721302, India.
authors.forename: K
authors.initials: K
authors.lastname: Kumari
authors.affiliation: Rubber Technology Centre, ‡School of Medical Science and Technology, and §Department of Biotechnology, Indian Institute of Technology , Kharagpur 721302, India.
authors.forename: T K
authors.initials: TK
authors.lastname: Maiti
authors.affiliation: Rubber Technology Centre, ‡School of Medical Science and Technology, and §Department of Biotechnology, Indian Institute of Technology , Kharagpur 721302, India.
authors.forename: M
authors.initials: M
authors.lastname: Mandal
authors.affiliation: Rubber Technology Centre, ‡School of Medical Science and Technology, and §Department of Biotechnology, Indian Institute of Technology , Kharagpur 721302, India.
authors.forename: S
authors.initials: S
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D004354:Drug Screening Assays, Antitumor; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006358:Hot Temperature; D006801:Humans; D008823:Micelles; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D004317:Doxorubicin
keywords: biocompatibility; doxorubicin; drug delivery; smart micelle; thermoresponsive polymer