PORPHYRIN FUNCTIONALIZED GOLD NANOPARTICLE FOR TARGETED DRUG DELIVERY IN CANCER

Background: Recently targeted drug delivery is a compelling task in cancer therapy. Nanocarriers have been designed as a useful platform for drug delivery. But in most the cases their inability of controlled release, poor site-specific accumulation, lack of stability, inability to cross the barriers of tumor microenvironment is difficult to overcome. Besides, they are prepared through chemical procedures which is environmental hazardous. Current investigation on targeted drug delivery is to use nanoparticle as ‘magic bullets’ that efficiently overcome all the difficulties. Methods: Sodium salts of tetrakis (4-sulphonatophenyl)-porphyrin (TPPS) functionalized gold nanoparticles (AuNPs) have been prepared in a ‘Green synthesis’ procedure. Here the porphyrin acts as reducing agent as well as stabilizing agent. Characterization of nanoparticle was done by UV-vis spectroscopy, TEM, DLS and XRD. Stability of the nanoparticle was checked in various pH buffer solutions and salt mediums by UV-vis spectroscopy. The dose dependent toxicity study of nanocarriers was performed in normal lung fibroblast upto 60 mg/ml. Next nanoparticle conjugated doxorubicin (DOX) was incorporated in glioblastoma multiforme cells, which was monitored using confocal microscopy, flow cytometry, scratch wound assay and western bolt analysis. Finally pH-dependent uncapping efficiency of DOX-loaded TPPS-AuNPs was studied at 37⁰C to evaluate the feasibility of using this nanoconjugate to target cancer tissue. Results: The synthesized nanoparticles are 20 nm in diameter and FCC structure in solid state. The nanoparticles are found to be very much stable and nontoxic to normal cell. We found that nanoparticle conjugated DOX has higher uptake potency (~7 times) compared to DOX only. As nanoparticle conjugated DOX (Dox@TPPS-AuNPs) was uptaken higher compared to DOX only by the cancer cell at the same time limit, so it shows highly toxicity towards cancer cell at same concentration of drug. We further showed that DOX@TPPS-AuNPs has more potent for the inhibition of cellular metastasis, cell cycle arrest and upregulation of apoptotic related molecules. Many effective drugs do not release from its conjugated counterpart in acidic tumor micro environment. Finally pH dependent release experiment shows an efficient release (~80%) of DOX occurs from TPPS-AuNPs surface in low pH environment. Conclusion: The stability, non-toxicity, controlled and efficient release of drug in cancer environment makes TPPS-AuNPs as an ideal drug carrier. So, it may be implemented as a better therapeutics for the targeted treatment of cancer.