Curcumin-loaded magnetic nanoparticles for breast cancer therapeutics and imaging applications

Abstract

Background:The next generation magnetic nanoparticles (MNPs) with theranostic applications have attracted significant attention and will greatly improve nanomedicine in cancer therapeutics. Such novel MNP formulations must have ultra-low particle size, high inherent magnetic properties, effective imaging, drug targeting, and drug delivery properties. To achieve these characteristic properties, a curcumin-loaded MNP (MNP-CUR) formulation was developed. Methods: MNPs were prepared by chemical precipitation method and loaded with curcumin (CUR) using diffusion method. The physicochemical properties of MNP-CUR were characterized using dynamic light scattering, transmission electron microscopy, and spectroscopy. The internalization of MNP-CUR was achieved after 6 hours incubation with MDA-MB-231 breast cancer cells. The anticancer potential was evaluated by a tetrazolium-based dye and colony formation assays. Further, to prove MNP-CUR results in superior therapeutic effects over CUR, the mitochondrial membrane potential integrity and reactive oxygen species generation were determined. Magnetic resonance imaging capability and magnetic targeting property were also evaluated. Results: MNP-CUR exhibited individual particle grain size of ∼9 nm and hydrodynamic average aggregative particle size of ∼123 nm. Internalized MNP-CUR showed a preferential uptake in MDA-MB-231 cells in a concentration-dependent manner and demonstrated accumulation throughout the cell, which indicates that particles are not attached on the cell surface but internalized through endocytosis. MNP-CUR displayed strong anticancer properties compared to free CUR. MNP-CUR also amplified loss of potential integrity and generation of reactive oxygen species upon treatment compared to free CUR. Furthermore, MNP-CUR exhibited superior magnetic resonance imaging characteristics and significantly increased the targeting capability of CUR. Conclusion: MNP-CUR exhibits potent anticancer activity along with imaging and magnetic targeting capabilities. This approach can be extended to preclinical and clinical use and may have importance in cancer treatment and cancer imaging in the future. Further, if these nanoparticles can functionalize with antibody/ligands, they will serve as novel platforms for multiple biomedical applications.

Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer

“…In this study, we demonstrate improved anti-cancer efficacy of PLGA-CUR NPs with in vitro and in vivo tumorigenic assays (Figure 2–4). The improved anti-cancer efficacy of our PLGA-CUR NP formulation is in accordance with previous studies [16, 49]. It is thought that NP formulations are more effective due to the sustained drug release over time compared to the short exposure to free CUR.…”

“…However, clinical translation of CUR is substantially hindered due to poor pharmacokinetics and insufficient bioavailability at the primary tumor as well as metastatic sites. Incorporating CUR into a nanoformulation may be very useful for patient treatment and is a viable option [14, 16]. Curcumin nanoformulations may target tumor tissue through either passive or active mechanisms that will improve its activity.…”

“…To-date a number of drug delivery strategies have been adopted to incorporate or encapsulate curcumin in polymer nanoparticles (NPs), liposomes, inclusion complex, and self-assemblies utilizing their complex molecular structures. This resulted in active binding and enhanced uptake by the cancer cells and thus exhibited enhanced anti-cancer activity [14–16]. Poly(lactic- co -glycolic acid) (PLGA) based nanoformulations are non-toxic, biodegradable and non-immunogenic and are thus valuable in medical applications [17].…”

Nanoways to overcome docetaxel resistance in prostate cancer

“…These magnetic nanoparticles have shown increased reactive oxygen species levels in prostate cancer cells and lower cell viability leading to enhanced cell death and increased expression of NF-κB in DU145 cells (Sato et al, 2013). Recent studies suggest that multi-layer magnetic nanoparticle system(s) has been highly encouraged due to their theranostic (therapy and imaging/diagnosis) applications in cancer (Yallapu et al, 2013b; Yallapu et al, 2010a; Yallapu et al, 2012b; Yallapu et al, 2011). Yazdi et al (Yazdi et al, 2012) synthesized a magnetic nanoparticle loaded with docetaxel which showed higher cytotoxicity than the free drug in cancer cells and this delivery system can be used to inhibit development of resistance in cancer cells.…”

Plasma Proteins Interaction with Curcumin Nanoparticles: Implications in Cancer Therapeutics

“…From this it can be considered that oleic acid layered magnetic NPs have enriched lipoproteins and albumin while complement and immunoglobulin proteins likely escape the immune system and RES. With this in mind, we have generated oleic acid/cyclodextrin layers with Pluronic polymer stabilizers for delivery of curcumin/doxorubicin [75, 76]. …”