title: "Gold nanoparticles composite-folic acid conjugated graphene oxide nanohybrids" for targeted chemo-thermal cancer ablation: In vitro screening and in vivo studies.
abstract: Nano-graphene oxide (GO) nanometal composite (specifically nanogold and nanosilver) have shown to be a promising material for anticancer therapeutics. Owing to their high drug loading capacity, photothermal and synergizing effects, it is very important to exploit them for targeted chemo-thermal cancer therapeutics. In this work, gold nanoparticles (AuNPs) were selected as the composite metal, folic acid (FA) was taken as GO surface functionalization moiety for active tumor targeting of model anticancer drug Doxorubicin (Dox). AuNPs composite-folate conjugated graphene oxide (FA-GO@Au) nano-platforms were synthesized and characterized in detail. Near-infrared (NIR) sensitivity resulted in an aggravated release of both Dox and ionic gold from the nanohybrid surface. Simultaneous delivery of Dox and AuNPs in the cellular vicinity was further enhanced after localized NIR exposure which resulted in significantly improved cancer cell toxicity. Mechanistic evaluation revealed G0/G1 phase arrest due to increased DNA intercalation and provoked early apoptosis under NIR influence. Pharmacokinetics and organ distribution studies were carried out in healthy mice and rabbits to estimate the actual bio fate of these nanohybrids. In vivo studies showed substantial tumor regression in solid tumor model in Balb/c mice and NIR exposure induced photo-thermal effects further resulted in better tumor management. Study provides substantial evidences both at in vitro and in vivo level to support the fact that NIR induced local photo-thermal effects can solely be used as a tumor targeting tool. This NIR dependent nanohybrid approach presents a precise and flexible strategy for targeted chemotherapy and photo-thermal tumor ablation.
authors.affiliation: Department of Pharmaceutics, Nanomedicine Research Centre, Indo Soviet Friendship College of Pharmacy, Moga, Punjab Technical University, Kapurthala, Punjab, 142001, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Chauhan
authors.affiliation: Centre for Nanosciences, Department of Chemical Engineering, Indian Institute of Technology Kanpur, Uttar Pradesh, India; Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, New Delhi, India.
authors.forename: Vianni
authors.initials: V
authors.lastname: Chopra
authors.affiliation: Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, New Delhi, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Tyagi
authors.affiliation: Department of Pharmaceutics, Nanomedicine Research Centre, Indo Soviet Friendship College of Pharmacy, Moga, Punjab Technical University, Kapurthala, Punjab, 142001, India.
authors.forename: Goutam
authors.initials: G
authors.lastname: Rath
authors.affiliation: Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, New Delhi, India.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Sharma
authors.affiliation: Department of Pharmaceutics, Nanomedicine Research Centre, Indo Soviet Friendship College of Pharmacy, Moga, Punjab Technical University, Kapurthala, Punjab, 142001, India. Electronic address: amitkumargoyal1979@gmail.com.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Goyal
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006046:Gold / Q000008:administration & dosage*; D006108:Graphite / Q000008:administration & dosage*; D006367:HeLa Cells; D006358:Hot Temperature / Q000627:therapeutic use; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D010087:Oxides / Q000008:administration & dosage; D047368:Tumor Burden / Q000187:drug effects / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D010087:Oxides; D006046:Gold; D006108:Graphite; D005492:Folic Acid
keywords: Gold nanoparticles, targeted chemotherapy; Graphene oxide; Near-infrared (NIR) sensitivity; Photo-thermal tumor ablation