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Engineered Exosomes for Stimuli-responsive Image-guided Drug delivery for Cancer Theranostic applications.

Periodic Reporting for period 1 - TheranoXome (Engineered Exosomes for Stimuli-responsive Image-guided Drug delivery for Cancer Theranostic applications.)

Período documentado: 2023-09-01 hasta 2025-08-31

The treatment of cancer has been one of the biggest challenges of modern medicine. This stems from the immense complexity of the disease arising due to its heterogenous nature. Different cancers respond to therapeutic treatment of drugs differently due to biological, physical and bio-chemical differences. Recent reports have highlighted that all cells in the body including cancer cells interact with each other through specific modes of communication-specifically through the use of exosomes; which are small lipid compartments in the nanoscale (~100 nm) that bleb off a cell and carry specific information and contain signatures on their surface that allow them to ´home´ to cells of the same type from where they arise. This project tries to utilize and harness this communication module to target cancer cells to deliver therapeutic agents specifically. Additionally, to improve and monitor the use of such exosomes for drug-delivery, it is also envisaged to couple stimuli-responsive and imageable nanoparticles to the exosomes in order to actuate site-specific remote-controlled drug delivery. Thus, the overall objective of this project is to develop a personalized strategy for the treatment of cancer that can be monitored during the treatment process, and can be actuated non-invasively to deliver therapeutic drugs at the target site and time.
The work done in this project included the following:
1.) Synthesized exosome mimicking cell-membrane nanovesicles (cellsomes) and stimuli-responsive inorganic iron-oxide nanoparticles
2.) Undertook the chemical coupling of cellsomes and iron-oxide nanoparticles to synthesize a novel stimuli-responsive hybrid nanoparticle system
3.) Evaluated the physical, chemical and biological characteristics of the synthesized material and assessed its ability to target cancer cells
4.) Studied its ability to specifically deliver chemotherapeutic drugs to cancer cells and evaluated its potential for magnetic targeting.

Main achievements of the project:
1.) A new stimuli-responsive bio-mimetic nanoparticle system was developed that was less than 200 nm in size
2,) The synthesized material showed a favourable biological response – ability to ´home´ to cancer cells, and at the same time exhibit the ability to response to an external magnetic field stimulus
3.) The developed material when loaded with chemotherapeutic drugs was able to deliver drugs specifically and showed superior cancer cell cytotoxicity as compared to the drug alone
4.) Under the influence of an external magnetic field showed enhanced drug penetration was achieved in a complex 3D tumor environment
This project paves the pathway for the development of novel bio-mimetic nanoparticle systems that can be used for cancer therapy and diagnosis. By utilizing a novel chemical approach, a multitude of different nanoparticle systems are envisaged to be produced by combining cell-membrane nanoparticle systems from different cancer types and different stimuli-responsive nanoparticles that can be explored for efficient drug-delivery and targeted cancer treatment. Further research needs to be undertaken to evaluate its effectiveness for pre-clinical cancer therapy.
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