title: Angiopep2-functionalized polymersomes for targeted doxorubicin delivery to glioblastoma cells.
abstract: A targeted drug delivery nanosystem for glioblastoma multiforme (GBM) based on polymersomes (Ps) made of poly(dimethylsiloxane)-poly(2-methyloxazoline) (PDMS-PMOXA) diblock copolymers was developed to evaluate their potential to actively target brain cancer cells and deliver anticancer drugs. Angiopep2 was conjugated to the surface of preformed Ps to target the low density lipoprotein receptor-related protein 1 that are overexpressed in blood brain barrier (BBB) and glioma cells. The conjugation efficiency yield for angiopep2 was estimated to be 24%. The angiopep2-functionalized Ps showed no cellular toxicity after 24h and enhanced the cellular uptake around 5 times more in U87MG glioblastoma cells compared to the non-targeted Ps. The encapsulation efficiency of doxorubicin (DOX) in Ps was 13% by co-solvent method, compared to a film rehydration method (4%). The release profiles of the DOX from Ps showed a release of 42% at pH 5.5 and 40% at pH 7.4 after 24h, indicating that Ps can efficiently retain the DOX with a slow release rate. Furthermore, the in vitro antiproliferative activity of DOX-loaded Ps-Angiopep2 showed enhanced toxicity to U87MG glioblastoma cells, compared to non-targeted Ps. Overall, our in vitro results suggested that angiopep2-conjugated Ps can be used as nanocarriers for efficient targeted DOX delivery to glioblastoma cells.
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Figueiredo
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: vimalkumar.balasubramanian@helsinki.fi.
authors.forename: Vimalkumar
authors.initials: V
authors.lastname: Balasubramanian
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Shahbazi
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Correia
authors.affiliation: Department of Chemistry, University of Basel, Klingelbergstrasse 80, CH-4056 Basel, Switzerland.
authors.forename: Dalin
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Chemistry, University of Basel, Klingelbergstrasse 80, CH-4056 Basel, Switzerland.
authors.forename: Cornelia G
authors.initials: CG
authors.lastname: Palivan
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Jouni T
authors.initials: JT
authors.lastname: Hirvonen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: helder.santos@helsinki.fi.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D045744:Cell Line, Tumor / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics*; D065546:Drug Liberation; D006801:Humans; D010455:Peptides / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry
chemical_list: C531860:Angiopep-2; D004129:Dimethylpolysiloxanes; D004337:Drug Carriers; D010455:Peptides; D011073:Polyamines; C117403:poly(2-methyl-2-oxazoline); C013830:baysilon; D004317:Doxorubicin
keywords: Angiopep2; Cancer therapy; Drug delivery; Intracellular uptake; Polymersomes