Abstract
Nanoparticle-mediated targeted delivery of bioactive natural compounds has recently been gaining much interest for breast cancer therapy. Herein, phenyl boronic acid (PBA)-conjugated and pH-responsive ZnO nanoparticles (diameter ∼40 nm) were synthesized for the tumor tissue-specific delivery of curcumin. PBA conjugation facilitates the targeted delivery of curcumin to the sialic acid overexpressed in breast cancer cell membranes. Curcumin-loaded ZnO nanoparticles (ZnO-PBA-Curcumin) caused apoptotic cell death in MCF-7 human breast cancer cells by inducing oxidative stress and mitochondrial damage. Further, in vivo intravenous (i.v.) administration of ZnO-PBA-Curcumin was found to effectively decrease tumor growth in Ehrlich ascites carcinoma (EAC) tumor-bearing mice via the enhanced accumulation of curcumin. Interestingly, ZnO-PBA-Curcumin did not show any signs of systemic toxicity. The cytotoxic potential of the nanohybrid ZnO-PBA-Curcumin is attributed to the combinatorial cytotoxic effects of curcumin and ZnO in cancer cells. Collectively, ZnO-PBA-Curcumin may represent a potential treatment modality for breast cancer therapy. This study provides insight into the tumor cell targeting mechanism using PBA functionalization, and the anticancer efficacy of curcumin-loaded pH-sensitive nanohybrids can be attributed to the differential oxidative stress-inducing properties of curcumin and Zn+2 ions.
Highlights
Cancer is a pathophysiological condition marked by uncontrolled cell division and the production of heterogeneous cell populations, forming a malignant neoplasm [1]
This study provides insight into the tumor cell targeting mechanism using phenyl boronic acid (PBA) functionalization, and the anticancer efficacy of curcumin-loaded pH-sensitive nanohybrids can be attributed to the differential oxidative stress-inducing properties of curcumin and Zn+2 ions
There was no significant difference in size among ZnO and ZnO-PBA-Curcumin as observed from the transmission electron microscope (TEM) study
Summary
Cancer is a pathophysiological condition marked by uncontrolled cell division and the production of heterogeneous cell populations, forming a malignant neoplasm [1]. Several avenues have been explored for the treatment of this deadly disease, including chemotherapy, radiation, and surgery over the past several decades. Chemotherapy remains the first choice for breast cancer treatment, but deadly side effects resulting from these cytotoxic chemotherapeutics have posed hindrances along the way [2]. Nanoparticlemediated drug delivery systems (DDS) have emerged as promising tools in this direction, as they can be utilized for the treatment of various diseases by circumventing healthy body tissues, causing minimal cytotoxicity and cell death in the healthy tissues while targeting only the diseased tissues [3]. Nanocarriers can be targeted towards the cancer cells using specific ligands or antibodies, and they induce toxicity in cancer cells due to their inherent anticancer properties or the anticancer properties of the loaded drug or both, rendering them as multifunctional
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