title: Dual responsive nanogels for intracellular doxorubicin delivery.
abstract: Nanosized polymeric delivery systems that encapsulate drug molecules and release them in response to a specific intracellular stimulus are of promising interest for cancer therapy. Here, we demonstrated a simple and fast synthetic protocol of redox-responsive nanogels with high drug encapsulation efficiency and stability. The prepared nanogels displayed narrow size distributions and versatility of surface modification. The polymer precursor of these nanogels is based on a random copolymer that contains oligoethyleneglycol (OEG) and pyridyldisulfide (PDS) units as side-chain functionalities. The nanogels were prepared through a lock-in strategy in aqueous media via self cross-linking of PDS groups. By changing polymer concentration, we could control the size of nanogels in range of 80-115nm. The formed nanogels presented high doxorubicin (DOX) encapsulation efficiency (70% (w/w)) and displayed pH and redox-controlled drug release triggered by conditions mimicking the reducible intracellular environment. The nanogels displayed an excellent cytocompatibility and were effectively endocytosed by A2780CP ovarian cancer cells, which make them promising nanomaterials for the efficient intracellular delivery of anticancer drugs.
authors.affiliation: Polymer Laboratory, Chemistry Department, School of Science, University of Tehran, P.O. Box 14155-6455, Tehran, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Asadi
authors.affiliation: Polymer Laboratory, Chemistry Department, School of Science, University of Tehran, P.O. Box 14155-6455, Tehran, Iran. Electronic address: khoee@khayam.ut.ac.ir.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Khoee
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D004317:Doxorubicin; D011094:Polyethyleneimine
keywords: Doxorubicin; Nanogel; Redox responsive; Targeted drug delivery; pH responsive