Folic acid modified copper oxide nanoparticles for targeted delivery in in vitro and in vivo systems

Abstract

Copper oxide nanoparticles are known to exhibit toxic effects on a variety of cell types. In the present study, copper oxide nanoparticles were modified with folic acid for targeted delivery. The physicochemical properties of copper oxide nanoparticles (CuO NPs) and folic acid conjugated copper oxide nanoparticles (CuO-FA NPs) were studied by Dynamic light scattering (DLS), Field emission scanning electron microscopy (FE-SEM) and Fourier transform infrared spectroscopy (FTIR). To determine targeting efficacy, we have used folate receptor positive and folate receptor knock down human breast cancer cells MCF7. Flow cytometric analysis, generation of ROS and expression of apoptotic proteins (cleaved PARP, decreased p-BAD) indicated that most cell death occurred through apoptosis in CuO-FA NPs treated MCF7 cells. In the in vivo study, we used Dalton's lymphoma (DL) cell induced tumor in mice. We successfully delivered CuO and CuO-FA NPs through peritoneal injection after induction of the tumor. Reactive oxygen species (ROS), glutathione (GSH) was measured in DL cells isolated from tumor bearing mice. All of these data indicated that CuO-FA NPs was more effective in killing the tumor cells and successful reduction of the tumor was observed in CuO-FA NPs treated mice after 15 days of treatment. These findings have important implications for understanding the potential anticancer properties induced by folic acid modified CuO NPs.

Synthesis, microbial susceptibility and anti-cancerous properties of copper oxide nanoparticles- review

“…Copper Oxide Nanoparticles synthesised via precipitation method using Cupric acetate monohydrate as starting material and sodium hydroxide as reducing agent yielded leaf like structure at lower pH of 9-11 and needle like structure at higher pH of 12 and more [27]. Copper Oxide Nanoparticles of crystalline nature was obtained by reducing copper (II) acetate with sodium hydroxide as exhibited by XRD pattern and TEM and SEM images with particle size of 22 nm, 23 nm and 35 nm as confirmed by Siddiqui et al Maqsood Ahmad et al and Laha Et al respectively in different experiments [23,30,31]. Another method of thermal decomposition of the precursor Cu 4 (SO 4 )(OH) 6 (brochantite one of cupric sulphates) made by sonication of CuSO 4 .5H 2 O (Copper (II) sulphate pentahydrate) and Na 2 CO 3 (Sodium Carbonate) yielded Copper Oxide Nanoparticles of spherical shape with diameters ranging from 50 to 100 nm [22].…”

“…Laha et al [31] converted the Copper Oxide Nanoparticles to Folic Acid conjugated NP since they can bond with Folate receptors that are over expressed in tumour and can be passively absorbed. The Copper Oxide Nanoparticles synthesized by this method showed size of 35±3 nm in FESEM.…”

“…Various studies are being carried out to study the effect of Copper Oxide Nanoparticles on pathogenic microorganisms i.e. (Antimicrobial efficacy [22][23][24][25]27]) and its cytotoxicity against cancer cell lines [27][28][29][30][31]. Copper Oxide being a transition metal oxide exhibits oxidative stress on cytoplasmic membrane which is the main reason for its cytotoxic property even in low dose.…”

“…Copper Oxide being a transition metal oxide exhibits oxidative stress on cytoplasmic membrane which is the main reason for its cytotoxic property even in low dose. Copper Oxide Nanoparticles synthesized using various methods exhibit different characteristics and have different impact on cell lines or we can say that they have different level of cytotoxicity on cancer cell lines [27][28][29][30][31][32][33].…”

Superparamagnetic Gadolinium Ferrite Nanoparticles with Controllable Curie Temperature – Cancer Theranostics for MR‐Imaging‐Guided Magneto‐Chemotherapy

“…50 µg mL –1 ). The time‐dependent toxicity is shown in Figure b, and the results demonstrate that the toxicity of DOX‐loaded GdIO NPs radically increases after 8 h, and almost 95 % killing was observed within 24 h. The drastic change in toxicity after 8 h could be explained by the observation that the FA‐mediated endocytosis occurs within 4–5 h, and after endocytosis, the drug could be co‐localized in the cytoplasm and started to react with the cells, which resulted in relatively slow cell killing , …”