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Stimuli Responsive Ultrabright Biomimetic NanoGhost for Targeted Solid Tumor Theranostics

Implementing Organization

Principal Investigator
Dr. RAJENDRA PRASAD
Indian Institute Of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh
rajendra.bce@iitbhu.ac.in
CO-Principal Investigator
Nil

Project Overview

Various stimuli active imaging agents have been studied for cancer diagnostics at various stages. Among them, optically active imaging agents (mainly organic fluorophores) have gained massive attention to delineate tumor location with deep tissue visualization in pre-clinical tumor models due to unique electronic transition, optical density and low light scattering. However, these imaging agents suffer with low photostability, low quantum yield (2-3 % only), low blood circulation (a few minutes), easy clearance and degradation, non-specific biodistribution (meant for healthy organ accumulation), poor tumor targeting and entry (less than 1 %). On the other hand, several quantum dots (both metallic and non-metallic) have been studied for cancer imaging, but they are limited with low biocompatibility though these are better with quantum yield and photostability. To the best of my knowledge, several nanoparticles-based imaging systems which entrap aforementioned optically active imaging probes have been proposed and studied for cancer imaging especially solid tumor imaging. These stimuli responsive i.e. optically active nano sized imaging agents exhibit better colloidal stability, better biocompatibility, enhanced blood circulation (in hours), high photostability, localized biodistribution, etc. However, complicated engineering, low reproducibility, batch to batch variability, uncontrolled particle size, poor encapsulation capacity, etc. are still major limitations. More specifically, poor tumor targeting (less than 1 %) and retention which depend on enhanced permeability and retention (EPR) mechanism are being questioned in the translational nanomedicine area. The clear mechanism for tumor entry and exit of nano sized imaging agents is not yet known though there were few reports by Warren Chan and workers (Nature materials, 2020, 19(5), 566, Nature Materials, 2023, 22(10), 1261). It should be noted that imaging agents should exhibit enough brightness from the targeted site to visualize tumor clearly. To improve site-selective tumor targeting, NanoGhosts (NGs) particles which will be reconstructed from the cell membrane. These NGs would be integrated with organic fluorophores for tumor imaging with significant emissive signals. Moreover, the proposed NGs would have (i) natural surface biomarkers to mimic their biological response named as biomimetic (ii) would be able to integrate amphiphilic and lipophilic imaging agents which would also alter their brightness. Further, the proposed ultrabright biomimetic NGs systems would evade immune cell recognized which would improve their targeting ability. More importantly, preventing pre-mature leakage of loaded cargo would enable the high-contrast fluorescence signals from tumor site. The available natural surface biomarkers on NGs would exhibit high precision in tumor detection and strong tumor retention without affecting healthy tissues.
Funding Organization
Quick Information
Area of Research
Life Sciences & Biotechnology
Focus Area
Health Sciences
Start Date
29 Mar 2025
End Date
28 Mar 2028
Status
ongoing
Output
No. of Research Paper
00
Technologies (If Any)
00
No. of PhD Produced
00
Publications
00
No. of Patents
Filed : 00
Grant : 00
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