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Death receptor-5 targeted lipid nanoparticles of γ-secretase inhibitor for simultaneous targeting of breast cancer cells and cancer stem cells

Implementing Organization

Nagaland University
Principal Investigator
Dr. Hanumant Singh Rathore
Nagaland University, Nagaland
hanu7862007@yahoo.com
Principal Investigator
Dr. Praveen T.K.
J.S.S. College of Pharmacy, Ootcamund, Ooty, Tamil Nadu
praveentk7812@gmail.com
CO-Principal Investigator
Dr. Ashish Wadhwani
J.S.S. College of Pharmacy, Ootcamund, Ooty, Tamil Nadu
dradwadhwani@jsscpooty.org

About

The tumor metastasis, chemoresistance and tumor relapse have emerged as a major challenge in the treatment of triple negative breast cancer (TNBC). Recently it was discovered that small population of tumor initiating cells called breast cancer stem cells (BCSCs) are responsible for it. Currently available drugs target only tumor cells (non-BCSCs), while sparing BCSCs. Therefore, there is a need for therapeutic agents which target and eliminate both. Notch signaling pathway is a regulatory pathway responsible for angiogenesis in bulk tumor cells (non-BCSCs) and self renewal & maintenance in BCSCs. Inhibition of γ secretase is an attractive strategy to silence notch signaling. However, the clinical application of γsecretase inhibitors is limited due their non-selective toxicity to healthy cells. The purpose of the present study, therefore, is to design an active targeted delivery system for γ-secretase inhibitor, DAPT to achieve radical cure of TNBC.

Achievements

We have successfully formulated the DAPT loaded SLNs(DAPT@SLNs)and characterised. We have successfully tethered the DR5mAb to the developed DAPT@SLNs and prepared DR5-DAPT@SLNs. We have performed the statistical analysis and published 2 SCI indexed articles. We have studied the pharmacokinetics, biodistribution and biocompatibility of the developed DR5-DAPT@SLNs. The developed formulation DR5-DAPT@SLNs were tested for their efficacy and safety in in vivo breast cancer mice models. The results suggest that the developed formulation had better target-specificity and anti-cancer profile. We have performed the statistical analysis and published 2 SCI indexed articles.

Keywords

cancer stem cells, Department of Science and Technology (DBT), Death receptor-5 targeted lipid nanoparticles of γ-secretase inhibitor for simultaneous targeting of breast cancer cells and cancer stem cells, Medical Sciences, Cancer Therapeutics, Nanomedicine, Dr. Hanumant Singh Rathore, Nagaland University, Nagaland, Dr. Praveen T.K., J.S.S. College of Pharmacy, Ootcamund, Ooty, Tamil Nadu, Dr. Ashish Wadhwani, J.S.S. College of Pharmacy, Ootcamund, Ooty, Tamil Nadu

Source

Source
E-promis and Information received by Investigator
Funding Organization
Funding Organization
Department of Science and Technology (DBT)
Quick Information
Area of Research
Medical Sciences
Focus Area
Cancer Therapeutics, Nanomedicine
Start Date
2021
End Date
2025
Status
Completed
Output
No. of Research Paper
00
Technologies (If Any)
00
No. of PhD Produced
00
Publications
01
No. of Patents
Filed : 00
Grant : 00
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