title: Synergistically enhanced selective intracellular uptake of anticancer drug carrier comprising folic acid-conjugated hydrogels containing magnetite nanoparticles.
abstract: Targeted drug delivery has long been extensively researched since drug delivery and release at the diseased site with minimum dosage realizes the effective therapy without adverse side effects. In this work, to achieve enhanced intracellular uptake of anticancer drug carriers for efficient chemo-therapy, we have designed targeted multifunctional anticancer drug carrier hydrogels. Temperature-responsive poly(N-isopropylacrylamide) (PNIPAm) hydrogel core containing superparamagnetic magnetite nanoparticles (MNP) were prepared using precipitation polymerization, and further polymerized with amine-functionalized copolymer shell to facilitate the conjugation of targeting ligand. Then, folic acid, specific targeting ligand for cervical cancer cell line (HeLa), was conjugated on the hydrogel surface, yielding the ligand conjugated hybrid hydrogels. We revealed that enhanced intracellular uptake by HeLa cells in vitro was enabled by both magnetic attraction and receptor-mediated endocytosis, which were contributed by MNP and folic acid, respectively. Furthermore, site-specific uptake of the developed carrier was confirmed by incubating with several other cell lines. Based on synergistically enhanced intracellular uptake, efficient cytotoxicity and apoptotic activity of HeLa cells incubated with anticancer drug loaded hybrid hydrogels were successfully achieved. The developed dual-targeted hybrid hydrogels are expected to provide a platform for the next generation intelligent drug delivery systems.
authors.affiliation: Department of Chemistry, Dong-A University, 37 Nakdong-daero 550 beon-gil, Saha-gu, Busan, 49315, Korea.
authors.forename: Haneul
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biological Science, Dong-A University, 37 Nakdong-daero 550 beon-gil, Saha-gu, Busan, 49315, Korea.
authors.forename: Ara
authors.initials: A
authors.lastname: Jo
authors.affiliation: Department of Chemistry, Dong-A University, 37 Nakdong-daero 550 beon-gil, Saha-gu, Busan, 49315, Korea.
authors.forename: Seulgi
authors.initials: S
authors.lastname: Baek
authors.affiliation: Department of Chemistry, Dong-A University, 37 Nakdong-daero 550 beon-gil, Saha-gu, Busan, 49315, Korea.
authors.forename: Daeun
authors.initials: D
authors.lastname: Lim
authors.affiliation: Department of Biological Science, Dong-A University, 37 Nakdong-daero 550 beon-gil, Saha-gu, Busan, 49315, Korea.
authors.forename: Soon-Yong
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Chemistry, Dong-A University, 37 Nakdong-daero 550 beon-gil, Saha-gu, Busan, 49315, Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Cho
authors.affiliation: Department of Biological Science, Dong-A University, 37 Nakdong-daero 550 beon-gil, Saha-gu, Busan, 49315, Korea.
authors.forename: Jin Woong
authors.initials: JW
authors.lastname: Chung
authors.affiliation: Department of Chemistry, Dong-A University, 37 Nakdong-daero 550 beon-gil, Saha-gu, Busan, 49315, Korea.
authors.forename: Jinhwan
authors.initials: J
authors.lastname: Yoon
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000493:pharmacokinetics*; D005492:Folic Acid / Q000493:pharmacokinetics*; D006367:HeLa Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000493:pharmacokinetics*; D058185:Magnetite Nanoparticles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D020100:Hydrogels; D058185:Magnetite Nanoparticles; D004317:Doxorubicin; D005492:Folic Acid