title: Radio-frequency triggered heating and drug release using doxorubicin-loaded LSMO nanoparticles for bimodal treatment of breast cancer.
abstract: Radio-frequency responsive nanomaterials combined with drugs for simultaneous hyperthermia and drug delivery are potential anti-cancer agents. In this study, chitosan coated La0.7Sr0.3MnO3 nanoparticles (C-LSMO NPs) were synthesized and characterized by X-ray diffraction, dynamic light scattering, Fourier transform infra red spectroscopy, vibrating sample magnetometer, scanning electron and atomic force microscopy. Under low radio-frequency (365kHz, RF), C-LSMO NPs (90nm) showed good colloidal stability (+22mV), superparamagnetic nature (15.4 emu/g) and heating capacity (57.4W/g SAR value). Chitosan facilitated doxorubicin entrapment (76%) resulted in DC-LSMO NPs that showed drug release upon a 5min RF exposure. MCF-7 and MDA-MB-231 cancer cells responded to a 5min RF exposure in the presence of bimodal DC-LSMO NPs with a significant decrease in viability to 73% and 88% (Pearson correlation, r=1, P<0.01) respectively, as compared to hyperthermia alone. Internalization of DC-LSMO NPs via the endosomal pathway led to an efficient localization of doxorubicin within the cell nucleus. The ensuing DNA damage, heat shock protein induction, and caspase production triggered apoptotic cell death. Moreover, DC-LSMO NPs successfully restricted the migration of metastatic MDA-MB-231 cancer cells. These data suggest that DC-LSMO NPs are potential bimodal therapeutic agents for cancer treatment and hold promise against disease recurrence and drug resistance.
authors.affiliation: Nanobioscience, Agharkar Research Institute, G.G. Agarkar Road, Pune 411004, India.
authors.forename: Vaishnavi M
authors.initials: VM
authors.lastname: Kulkarni
authors.affiliation: Nanobioscience, Agharkar Research Institute, G.G. Agarkar Road, Pune 411004, India.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Bodas
authors.affiliation: Polymer Science and Engineering Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India.
authors.forename: Deepa
authors.initials: D
authors.lastname: Dhoble
authors.affiliation: Nanobioscience, Agharkar Research Institute, G.G. Agarkar Road, Pune 411004, India. Electronic address: vandanaghormade@aripune.org.
authors.forename: Vandana
authors.initials: V
authors.lastname: Ghormade
authors.affiliation: Nanobioscience, Agharkar Research Institute, G.G. Agarkar Road, Pune 411004, India. Electronic address: kmpaknikar@aripune.org.
authors.forename: Kishore
authors.initials: K
authors.lastname: Paknikar
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D005260:Female; D006361:Heating; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004317:Doxorubicin
keywords: Anti-cancer; Chitosan-coated-LSMO nanoparticles; Drug delivery; Hyperthermia