Abstract

Enzymatic gold nanoparticles (B-GNPs) have been synthesized using a natural anticancer agent bromelain (a cysteine protease) and these nanoparticles were used to bioconjugate Cisplatin (highly effective against osteosarcoma and lung cancer). Cisplatin bioconjugated bromelain encapsulated gold nanoparticles (B-C-GNPs) were found profoundly potent against same cancers at much lower concentration with minimum side effects due to the synergistic effect of bromelain. The B-C-GNPs have been observed to inhibit the proliferation of osteosarcoma cell lines Saos-2 and MG-63 with IC50 estimation of 4.51 µg/ml and 3.21 µg/ml, respectively, and against small lung cancer cell line A-549 with IC50 2.5 µg/ml which is lower than IC50 of cisplatin against same cell lines. The B-GNPs/B-C-GNPs were characterized by TEM, UV-Visible spectroscopy, Zeta potential and DLS to confirm the production, purity, crystalline nature, stability of nanoemulsion, size and shape distribution. The change in 2D and 3D conformation of bromelain after encapsulation was studied by Circular Dichroism and Fluorometry, respectively. It was found that after encapsulation, a 19.4% loss in secondary structure was observed, but tertiary structure was not altered significantly and this loss improved the anticancer activity. The confirmation of bioconjugation of cisplatin with B-GNPs was done by UV-Visible spectroscopy, TEM, FTIR, 2D 1H NMR DOSY and ICP-MS. Further, it was found that almost ~4 cisplatin molecules bound with each B-GNPs nanoparticle.

Highlights

  • In both industrialized and developing countries, there is an increase in the number of reported cases of cancer

  • For the treatment of osteosarcoma different nanomaterials conjugated with the chemotherapy drugs such as LDH conjugated with methotrexate[30], polymerized liposome nanoparticles conjugated with doxorubicin[31] and calcium phosphate and lipid modified dextran nanoparticles conjugated with cisplatin and doxorubicin respectively[32,33], have been used which proved the increase in efficacy of the drugs

  • Www.nature.com/scientificreports group of bromelain and –NH2 group of cisplatin was performed by Ethyl-3-(3-dimethyl) carbodiimide (EDC) and its confirmation was done by UV, Transmission Electron Microscope (TEM), FTIR and 1H1 Nuclear magnetic resonance (NMR) DOSY

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Summary

Introduction

In both industrialized and developing countries, there is an increase in the number of reported cases of cancer. Engineered nanoparticles become a significant tool in the treatment of cancer They have the ability to either enhance the delivery of drugs, or uptake by target cells and/or reduce the toxic effect of free drug to other organs. Developments in the field of nanotechnology are quite vigorous from the past few years and one of its important applications is targeted drug delivery This can offer novel ways to deliver anticancer drugs to individual cancer cells and capable in detection of cancer[29]. For the treatment of osteosarcoma different nanomaterials conjugated with the chemotherapy drugs such as LDH conjugated with methotrexate[30], polymerized liposome nanoparticles conjugated with doxorubicin[31] and calcium phosphate and lipid modified dextran nanoparticles conjugated with cisplatin and doxorubicin respectively[32,33], have been used which proved the increase in efficacy of the drugs. On conclusion of the reaction, the unbound bromelain was expelled by using 50% v/v of ethanol followed by centrifugation (30,000 g, 30 min.), rinsed two times with milli Q water and utilized for further characterization

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