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Journal of Nuclear Medicine

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Meeting ReportOncology: Basic & Translational -> Basic Science (O)

A Novel Approach for Site Specific Delivery of Anticancer Drug Using Peptide Functionalized Metallic Nanoconstruct

Kavita Bansal and Jaya Shukla
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 95;
Kavita Bansal
1Nuclear Medicine Post Graduate Institute of Medical Education & Research Chandigah India
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Jaya Shukla
2Nuclear Medicine Post Graduate Institute of Medical Education & Research Chandigarh India
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Abstract

95

Aim: Nanomaterial based structures exhibit enhanced optical and chemical properties and are widely used in development of highly efficient drug delivery systems. But owing to their toxic effects, their utmost usage in therapies is still under review. The gold nanoparticles (GNPs) synthesized by employing conventional methodology suffer from low stability in the presence of cationic peptide and limited their uses in biological applications. To overcome this problem, we designed a facile process for the synthesis of amino acid reduced gold nanocarriers for the efficient delivery of potent anti-cancer drug doxorubicin (Dox).

Methods: The carboxylic acid functionalized GNPs were synthesized by the direct reduction of gold salt with aspartic acid, which subsequently capped the gold particle surface. Subsequently, aspartic acid capped nanoparticles were functionalized by TAT cell penetrating peptide by both covalent and non-covalent approaches. The cell viability assay and cellular uptake studies in cervical cancer cells (HeLa) were analyzed by MTT assay and confocal microscope respectively. Subsequently, the developed nanocarriers were used for loading of doxorubicin. The pH responsive release of drug was observed in different phosphate buffer solutions prepared at pH-5, pH-6.8, and pH-7.4, corresponding to lysosome, tumor and normal tissues environment respectively. To access the cytotoxic activity and intracellular uptake of developed nano-chemotherapeutic system MTT assay and fluorescence imaging were employed. RESULTS The high loading of peptide (81.6% ±1.84 %) on GNPs was achieved using both covalent and non-covalent approaches and was approximately double compared to the conventional approach (42.3%±1.58%). Further, stability studies in different electrolytes confirmed their high suitability for biological studies. The cellular uptake studies and cell viability assay confirmed that the nanocarriers were able to translocate in the cells and remained non-toxic to the cells (>90% viability). Moreover, the synthesized conjugates hold good potential was used as a carrier vehicle in the delivery of doxorubicin. The developed chemotherapeutic system showed enhanced drug release (>80%) at acidic pH as compared to physiological pH (25%), confirming its potential to be used for tumor treatment. The internalization of chemotherapeutic system was visualized by confocal microscopy. The results clearly elucidate that the TAT plays an important role in the cellular internalization. The MTT results illustrated that due to the presence of TAT, the cytotoxic efficiency of drug with chemotherapeutic system was increased twice (IC50-2.5µg) as compared to the free drug molecules. Henceforth, the results indicated a facile and novel approach for the development of highly efficient and biocompatible drug delivery systems for cancer therapeutics.

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Journal of Nuclear Medicine
Vol. 61, Issue supplement 1
May 1, 2020
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A Novel Approach for Site Specific Delivery of Anticancer Drug Using Peptide Functionalized Metallic Nanoconstruct
Kavita Bansal, Jaya Shukla
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 95;

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A Novel Approach for Site Specific Delivery of Anticancer Drug Using Peptide Functionalized Metallic Nanoconstruct
Kavita Bansal, Jaya Shukla
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 95;
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