Abstract
The aim of this study was to develop drug delivery nanosystems based on pegylated gold nanoparticles (PEGAuNPs) for a combination against pancreatic cancer cells. Doxorubicin and varlitinib, an anthracycline and a tyrosine kinase inhibitor respectively, were conjugated with gold nanoparticles. The systems were characterized, after synthesis, regarding their size, stability and morphology. An efficient conjugation of doxorubicin and varlitinib with PEGAuNPs was revealed. The cytotoxicity effect induced by the combination of the nanoconjugates was investigated in pancreatic cancer cell lines. Doxorubicin and varlitinib conjugated with PEGAuNPs revealed a combined effect to decrease the cell survival of the cancer line S2-013s, while reducing the drugs’ toxicity for the healthy pancreatic cells hTERT-HPNE. This study highlights the promising potential of PEGAuNPs for targeted delivery of therapeutic drugs into human cells, enhancing the antitumor growth-inhibition effect on cancer cells, and decreasing the toxicity against normal cells. In cancer therapy, the present approach based on PEGAuNP functionalization can be further explored to increase drug targeting efficiency and to reduce side effects.
Highlights
Nanoparticles (NPs) have been designed as targeted drug delivery systems for a myriad of applications in nanomedicine combining therapeutics and diagnosis [1]
Due to the enhanced permeability and retention (EPR) effect associated with tumor tissue vascularization, NPs can be accumulated at the targeted site, increasing their therapeutic potential, and their ability as a diagnostic tool for bioimaging techniques [2]
The aim of the present study was to evaluate the in vitro targeted delivery of two nanoconjugates at the same time—the polyethylene glycol-coated gold nanoparticles (PEGAuNPs) conjugated with doxorubicin (DoxPEGAuNPs); and the PEGAuNPs conjugated with varlitinib (ValPEGAuNPs), in pancreatic adenocarcinoma cells
Summary
Nanoparticles (NPs) have been designed as targeted drug delivery systems for a myriad of applications in nanomedicine combining therapeutics and diagnosis [1]. AuNPs present unique optical and physico-chemical characteristics such as small size, high colloidal stability, high surface-to-volume ratio, easy synthesis, and functionalization [2,7]. Their high tissue permeability and non-cytotoxicity make them suitable vectors for applications in nanomedicine such as therapeutic agents and effective nanocarriers for drug delivery [2,8,9,10,11,12]. The conjugation of the AuNPs with antitumoral drugs is an approach to enhance their activity, which reduces the uptake in normal tissues and consequentially undesired side effects [8]
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