title: Assessing Therapeutic Potential of Magnetic Mesoporous Nanoassemblies for Chemo-Resistant Tumors.
abstract: Smart drug delivery system with strategic drug distribution is the future state-of-the-art treatment for any malignancy. To investigate therapeutic potential of such nanoparticle mediated delivery system, we examined the efficacy of dual drug-loaded, pH and thermo liable lipid coated mesoporous iron oxide-based magnetic nanoassemblies (DOX:TXL-LMMNA) in mice bearing both drug sensitive (A2780(S)) and drug resistant (A2780-CisR) ovarian cancer tumor xenografts. In presence of an external AC magnetic field (ACMF), DOX:TXL-LMMNA particles disintegrate to release encapsulated drug due to hyperthermic temperatures (41-45 ºC). In vivo bio distribution study utilizing the optical and magnetic properties of DOX:TXL-LMMNA particles demonstrated minimum organ specific toxicity. Noninvasive bioluminescence imaging of mice bearing A2780(S) tumors and administered with DOX-TXL-LMMNA followed by the application of ACMF revealed 65% less luminescence signal and 80% mice showed complete tumor regression within eight days. A six months follow-up study revealed absence of relapse in 70% of the mice. Interestingly, the A2780-CisR tumors which did not respond to drug alone (DOX:TXL) showed 80% reduction in luminescence and tumor volume with DOX:TXL-LMMNA after thermo-chemotherapy within eight days. Cytotoxic effect of DOX:TXL-LMMNA particles was more pronounced in A2780-CisR cells than in their sensitive counterpart. Thus these novel stimuli sensitive nanoassemblies hold great promise for therapy resistant malignancies and future clinical applications.
authors.affiliation: 1. Centre for Research in Nanotechnology and Sciences, IIT Bombay, Mumbai, 400076,India.; 4. Department of Metallurgical Engineering and Materials Science, IIT Bombay, Mumbai, 400076 India.
authors.forename: Lina
authors.initials: L
authors.lastname: Pradhan
authors.affiliation: 2. Advance Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India.
authors.forename: Bhushan
authors.initials: B
authors.lastname: Thakur
authors.affiliation: 3. Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, 400076, India.
authors.forename: Rohit
authors.initials: R
authors.lastname: Srivastava
authors.affiliation: 2. Advance Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India.
authors.forename: Pritha
authors.initials: P
authors.lastname: Ray
authors.affiliation: 4. Department of Metallurgical Engineering and Materials Science, IIT Bombay, Mumbai, 400076 India.
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Bahadur
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers / Q000008:administration & dosage*; D004351:Drug Resistance; D005260:Female; D064593:Heterografts; D058185:Magnetite Nanoparticles / Q000008:administration & dosage*; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D004317:Doxorubicin
keywords: Cisplatin resistance; Combined thermo-chemotherapy effect.; Dual drug carrier; Fluorescence and Bioluminescence imaging; Mesoporous magnetic nanoassembly; Ovarian cancer xenografts