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PH-responsive and targeted delivery of curcumin via phenylboronic acid-functionalized ZnO nanoparticles for breast cancer therapy.

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.

SUBMITTER: Kundu M

PROVIDER: S-EPMC6479012 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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pH-responsive and targeted delivery of curcumin via phenylboronic acid-functionalized ZnO nanoparticles for breast cancer therapy.

Kundu Mousumi M Sadhukhan Pritam P Ghosh Noyel N Chatterjee Sharmistha S Manna Prasenjit P Das Joydeep J Sil Parames C PC

Journal of advanced research 20190301

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 apopto ...[more]

PMID: 31032117

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Project description:Mercaptoundecanoic acid (MUA) functionalized gold nanoparticles (AuNP-MUA) were synthesized and demonstrated to possess pH-triggered aggregation and re-dispersion, as well as the capability of phase transfer between aqueous and organic phases in response to changes in pH. The pH of aggregation for AuNP-MUA is consistent with the pKa of MUA (pH ~4) in solution, while AuNP-MUA phase transition between aqueous and organic phases occurs at pH ~9. The ion pair formation between the amine group in octadecylamine (ODA), the carboxylate group in MUA, and the hydrophobic alkyl chain of ODA facilitates the phase transfer of AuNP-MUA into an organic medium. The AuNP-MUA were investigated as a reusable catalyst in the catalytic reduction of 4-nitrophenol by borohydride-a model reaction for AuNPs. It was determined that 100% MUA surface coverage completely inhibits the catalytic activity of AuNPs. Decreasing the surface coverage was shown to increase catalytic activity, but this decrease also leads to decreased colloidal stability, recoverability, and reusability in subsequent reactions. At 60% MUA surface coverage, colloidal stability and catalytic activity were achieved, but the surface coverage was insufficient to enable redispersion following pH-induced recovery. A balance between AuNP colloidal stability, recoverability, and catalytic activity with reusability was achieved at 90% MUA surface coverage. The AuNP-MUA catalyst can also be recovered at different pH ranges depending on the recovery method employed. At pH ~4, protonation of the MUA results in reduced surface charge and aggregation. At pH ~9, ODA will form an ion-pair with the MUA and induce phase transfer into an immiscible organic phase. Both the pH-triggered aggregation/re-dispersion and aqueous/organic phase transfer methods were employed for catalyst recovery and reuse in subsequent reactions. The ability to recover and reuse the AuNP-MUA catalyst by two different methods and different pH regimes is significant, based on the fact that nanoparticle-catalyzed reactions may occur under different pH conditions.

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PH-responsive and targeted delivery of curcumin via phenylboronic acid-functionalized ZnO nanoparticles for breast cancer therapy.

Publications

pH-responsive and targeted delivery of curcumin via phenylboronic acid-functionalized ZnO nanoparticles for breast cancer therapy.

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