title: A hyaluronic acid nanogel for photo-chemo theranostics of lung cancer with simultaneous light-responsive controlled release of doxorubicin.
abstract: The combined delivery of photo- and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid nanogel) that exerts an activity with multiple effects: thermo and chemotherapeutic, real-time noninvasive imaging, and light-glutathione-responsive controlled drug release. The nanogel is mono-dispersed with an average diameter of 120 nm as observed by using TEM and a hydrodynamic size analyzer. It has excellent photo-luminescence properties and good stability in buffer and serum solutions. Graphene itself, being photoluminescent, can be considered an optical imaging contrast agent as well as a heat source when excited by laser irradiation. Thus the nanogel shows simultaneous thermo-chemotherapeutic effects on noninvasive optical imaging. We have also found that irradiation enhances the release of doxorubicin in a controlled manner. This release synergizes therapeutic activity of the nanogel in killing tumor cells. Our findings demonstrate that the graphene-doxorubicin conjugate in the hyaluronic acid nanogel is very effective in killing the human lung cancer cell line (A549) with limited toxicity in the non-cancerous cell line (MDCK).
authors.affiliation: Department of Chemical & Biological Engineering, Korea National University of Transportation, Chungju, 380-702, Republic of Korea. leeyk@ut.ac.kr.
authors.forename: Zehedina
authors.initials: Z
authors.lastname: Khatun
authors.forename: Md
authors.initials: M
authors.lastname: Nurunnabi
authors.forename: Md
authors.initials: M
authors.lastname: Nafiujjaman
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Reeck
authors.forename: Haseeb A
authors.initials: HA
authors.lastname: Khan
authors.forename: Kwang Jae
authors.initials: KJ
authors.lastname: Cho
authors.forename: Yong-kyu
authors.initials: YK
authors.lastname: Lee
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000379:methods; D003287:Contrast Media; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D006108:Graphite / Q000528:radiation effects / Q000627:therapeutic use; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D008027:Light; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D058726:Nanoconjugates / Q000008:administration & dosage / Q000737:chemistry; D000080385:Nanogels; D009374:Neoplasms, Experimental / Q000473:pathology* / Q000628:therapy*; D010778:Photochemotherapy / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D000068936:Theranostic Nanomedicine; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D003287:Contrast Media; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D058726:Nanoconjugates; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D006108:Graphite; D004317:Doxorubicin; D011094:Polyethyleneimine; D006820:Hyaluronic Acid