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Theranostics 2016; 6(10):1557-1572. doi:10.7150/thno.15231 This issue Cite

Research Paper

Assessing Therapeutic Potential of Magnetic Mesoporous Nanoassemblies for Chemo-Resistant Tumors

Lina Pradhan^{1, 4*}, Bhushan Thakur^2*, Rohit Srivastava³, Pritha Ray^2✉, Dhirendra Bahadur^4✉

1. Centre for Research in Nanotechnology and Sciences, IIT Bombay, Mumbai, 400076,India.
2. Advance Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India.
3. Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, 400076, India.
4. Department of Metallurgical Engineering and Materials Science, IIT Bombay, Mumbai, 400076 India.
^*These authors contributed equally.

✉ Corresponding authors: Tel.: +91 22 2740 5119 (P. Ray). Tel.: +91 22 25767632 (D. Bahadur). E-mail addresses: praygov.in (P. Ray), dhirenbac.in (D. Bahadur).

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.

Keywords: Mesoporous magnetic nanoassembly, Dual drug carrier, Fluorescence and Bioluminescence imaging, Cisplatin resistance, Ovarian cancer xenografts, Combined thermo-chemotherapy effect.

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