Comparative cytotoxicity of gold–doxorubicin and InP–doxorubicin conjugates

Abstract

Direct comparisons of different types of nanoparticles for drug delivery have seldom been performed. In this study we compare the physical properties and cellular activity of doxorubicin (Dox) conjugates to gold nanoparticles (Au) and InP quantum dots of comparable diameter. Although the Au particles alone are non-toxic and InP is moderately toxic, Au-Dox is more effective than InP-Dox against the Dox-resistant B16 melanoma cell line. Light exposure does not augment the efficacy of InP-Dox, suggesting that conjugates are breaking down. Electron and confocal microscopy and atomic absorption spectroscopy reveal that over 60% of the Au-Dox conjugates reach the cell nucleus. In contrast, InP-Dox enters cell nuclei to a very limited extent, although liberated Dox from the conjugates does eventually reach the nucleus. These observations are attributed to faster Dox release from Au conjugates under endosomal conditions, greater aggregation of InP-Dox with cytoplasmic proteins, and adherence of InP to membranes. These findings have important implications for design of active drug-nanoparticle conjugates.

Efficient pH Dependent Drug Delivery to Target Cancer Cells by Gold Nanoparticles Capped with Carboxymethyl Chitosan

“…Chemoresistance is mainly due to over expression of a membrane transporter, p-glycoprotein (pgp) that actively pumps DOX out of the cell [33]. DOX conjugated nanoparticle based drug delivery system evades this mode of efflux as it is taken up by the cells efficiently through endocytosis [34,35]. Colloidal AuNPs incorporating anticancer agents can overcome resistance to drug action, thus reducing the need for higher doses and therefore reducing their ill effects towards normal cells [34,35].…”

“…DOX conjugated nanoparticle based drug delivery system evades this mode of efflux as it is taken up by the cells efficiently through endocytosis [34,35]. Colloidal AuNPs incorporating anticancer agents can overcome resistance to drug action, thus reducing the need for higher doses and therefore reducing their ill effects towards normal cells [34,35]. It has been long believed that tumors are acidic in nature through extensive studies using microelectrode measurements [36] or magnetic resonance spectroscopy images [37,38].…”

Induction of intrinsic apoptotic pathway and cell cycle arrest via baicalein loaded iron oxide nanoparticles as a competent nano-mediated system for triple negative breast cancer therapy

“…Thus, in order to create vehicle capable of carrying anticancer drug for targeting therapeutic purposes, we have developed drug loaded baicalein conjugated magnetic nanoparticles and shows efficient drug releasing property (Fig 9). The iron oxide nanoparticles showed a spherical shape as evident from the TEM and SEM analysis and the particle size was about 19nm 21 and doxorubicin coated poly (butylcyanoacrylate) nanoparticles (PBCA NPs) were highly stable spherical particles 22 . The results of our findings too are in accordance with these studies reported.…”

PLGA-loaded nanomedicines in melanoma treatment: Future prospect for efficient drug delivery

“…ABI-007 or NP albumin bound (nab)-paclitaxel has already been approved by the FDA for clinical use90. Zhang et al 91 demonstrated that doxorubicin (DOX) loaded gold NPs, a targeted chemotherapeutic agent, was very effective against a melanoma cell line. However, more studies are needed to streamline the treatment methodologies that can screen out the adverse side effects and only the beneficial effects could be delivered to the patients.…”