Coated Sirna Theranotic Naoparticle For Cancer Case Study

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RBC-Coated siRNA Theranostic Nanoparticle for Cancer

l. Specific Aims Cancer is a leading cause of death worldwide as accounted for 8.8 million deaths in 2015, nearly 1 in 6 deaths is due to cancer as per WHO Fact sheet. Technology has evolved for developing nano sized drugs for effective cancer therapy and diagnosis. PEGylation of nanoparticles allows significant extension of their biological half-life, reduction in toxicity, antigenicity and immunogenicity while sustaining therapeutic effectiveness. In contrast to the accepted general assumption that PEG is non-immunogenic and non-antigenic, animal studies clearly showed that PEGylated agents can elicit antibody formation against PEG (anti-PEG) while anti-PEG responses may limit
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To outline and quantify the the tumor region,diagnosis is performed pre and post the treatment. We aim to synthesize RBC membrane derived vesicles that would make it possible to be used for any patient, capable of coating a nanoparticle that can targeting the tumor cells using TF-TFR mechanism and knocking down RRM2 protein using siRNA as the therapeutic agent and 64Cu as diagnostic agent thus saving time and cost of the treatment5. We hypothesize that the RBC membrane derived vesicles will be a universal stealth agent for the nanoparticle surface. The nanoparticle will target the TFR (Transferrin receptor) and Ribonucleotide reductase M2 (RRM2) that is upregulated in the malignant cells. It will systemically administer siRNA to a human to produce a specific gene inhibition (reduction in mRNA and protein) by RNAi mechanism of action which will lead to reduction in RRM2 protein expression. The nanoparticle will be labelled with 64Cu which can be used for diagnosis using micro-PET imaging or CT imaging making the total approach theranostic.

Remove antigens from RBC surface followed by derivation of RBC membrane vesicles and characterize the RBC-membrane-derived vesicles. Specifically, we will: a) Remove the blood group defining antigen using a-galactosidase and 1-N-acetylgalactosaminidase derived enzyme and characterize using immunofluorescence,

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