title: Superparamagnetic Reduction/pH/Temperature Multistimuli-Responsive Nanoparticles for Targeted and Controlled Antitumor Drug Delivery.
abstract: Multistimuli-responsive polymeric nanoparticles with core-shell architecture were prepared by coating superparamagnetic Fe3O4 nanoparticle cores with reduction/pH dual-responsive poly(methacrylic acid) (PMAA) as shells and thermal-responsive poly(N-isopropylacrylamide) (PNIPAM) as a "gatekeeper" on the surface via two-stage distillation precipitation polymerization. The Fe3O4@PMAA nanoparticles were synthesized using N,N-bis(acryloyl)cystamine (BACy) as cross-linker which would be easily biodegradable in the presence of dithiothreitol (DTT) or glutathione (GSH). The cumulative release profile was investigated under different conditions, such as media pH, reductive agents, and temperature, with doxorubicin hydrochloride (DOX) as a model anticancer drug. They showed a low leakage of DOX at pH 7.4 (less than 11% in 24 h), while the release significantly accelerated at pH 5.0 and 10 mM GSH (over 60% in 5 h), realizing the "triggered release" of drug in the targeted tissues. The nanoparticles exhibited excellent biocompatibility while the DOX-loaded nanoparticles showed great promise of antitumor efficacy as free DOX by the MTT assay and CLSM analysis. The results suggest that the novel biodegradable nanoparticles with high drug loading capacity and multiresponsive controlled release capability could serve as an excellent gene/drug delivery system candidate for cancer therapy.
authors.affiliation: State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University , Lanzhou 730000, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University , Lanzhou 730000, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Du
authors.affiliation: State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University , Lanzhou 730000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University , Lanzhou 730000, China.
authors.forename: Jiagen
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University , Lanzhou 730000, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University , Lanzhou 730000, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University , Lanzhou 730000, China.
authors.forename: Xubo
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University , Lanzhou 730000, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D058105:Polymerization; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D013696:Temperature
chemical_list: D000180:Acrylic Resins; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D011108:Polymers; C052970:poly-N-isopropylacrylamide; D004317:Doxorubicin
keywords: antitumor drug delivery; controlled release; distillation precipitation polymerization; multiresponsive; polymer nanoparticles; superparamagnetic