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Improving anti-melanoma effect of curcumin by biodegradable nanoparticles.

ABSTRACT: Melanoma is known as the most common malignant cutaneous cancer. Curcumin, a natural component, has been shown to have various activities such as anti-oxidant, anti-septic, anti-inflammatory, anti-biotic, anti-amyloid and anti-thrombosis. However, there is a greatest obstacle in the administration of curcumin due to its hydrophobicity and low oral bioavailability. In this study, we formulated curcumin-loaded MPEG-PLA (Curcumin/MPEG-PLA) micelles aiming to improve its solubility in aqueous solution and investigated anti-tumor effect on melanoma in vitro and in vivo. The spherical curcumin/MPEG-PLA micelles were completely dispersed in normal saline and could release curcumin in a sustained manner in vitro. In addition, we demonstrated that curcumin/MPEG-PLA micelles had stronger cytotoxicity and induced a higher percentage of apoptosis in B16 and A375 cancer cells than free curcumin in vitro. The immunohistochemical study revealed that curcumin/MPEG-PLA micelles induced more melanoma cell apoptosis than free curcumin and inhibited neovascularization in tumor tissues. In conclusion, the curcumin/MPEG-PLA micelles have potential clinical application for melanoma.

SUBMITTER: Wang B

PROVIDER: S-EPMC5752469 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other

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Improving anti-melanoma effect of curcumin by biodegradable nanoparticles.

Wang Bilan B Liu Xiaoxiao X Teng Yan Y Yu Ting T Chen Junli J Hu Yuzhu Y Liu Na N Zhang Lingli L Shen Yangmei Y

Oncotarget 20170824 65

Melanoma is known as the most common malignant cutaneous cancer. Curcumin, a natural component, has been shown to have various activities such as anti-oxidant, anti-septic, anti-inflammatory, anti-biotic, anti-amyloid and anti-thrombosis. However, there is a greatest obstacle in the administration of curcumin due to its hydrophobicity and low oral bioavailability. In this study, we formulated curcumin-loaded MPEG-PLA (Curcumin/MPEG-PLA) micelles aiming to improve its solubility in aqueous soluti ...[more]

PMID: 29312556

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Project description:Breast cancer is the second leading cause of cancer-related death in women. The majority of breast tumors are estrogen receptor-positive (ER+) and hormone-dependent. Neoadjuvant anti-estrogen therapy has been widely employed to reduce tumor mass prior to surgery. Tamoxifen is a broadly used anti-estrogen for early and advanced ER+ breast cancers in women and the most common hormone treatment for male breast cancer. 4-Hydroxytamoxifen (4-OHT) is an active metabolite of tamoxifen that functions as an estrogen receptor antagonist and displays higher affinity for estrogen receptors than that of tamoxifen and its other metabolites. MicroRNA-21 (miR-21) is a small noncoding RNA of 23 nucleotides that regulates several apoptotic and tumor suppressor genes and contributes to chemoresistance in numerous cancers, including breast cancer. The present study investigated the therapeutic potential of 4-OHT and anti-miR-21 coadministration in an attempt to combat tamoxifen resistance, a common problem often encountered in anti-estrogen therapy. A biodegradable poly(d,l-lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG-COOH) copolymer was utilized as a carrier to codeliver 4-OHT and anti-miR-21 to ER+ breast cancer cells. 4-OHT and anti-miR-21 co-loaded PLGA-b-PEG nanoparticles (NPs) were developed using emulsion-diffusion evaporation (EDE) and water-in-oil-in-water (w/o/w) double emulsion methods. The EDE method was found to be best method for 4-OHT loading, and the w/o/w method proved to be more effective for coloading NPs with anti-miR-21 and 4-OHT. The optimal NPs, which were prepared using the double emulsion method, were evaluated for their antiproliferative and apoptotic effects against MCF7, ZR-75-1, and BT-474 human breast cancer cells as well as against 4T1 mouse mammary carcinoma cells. We demonstrated that PLGA-b-PEG NP encapsulation significantly extended 4-OHT's stability and biological activity compared to that of free 4-OHT. MTT assays indicated that treatment of MCF7 cells with 4-OHT-anti-miR-21 co-loaded NPs resulted in dose-dependent antiproliferative effects at 24 h, which was significantly higher than what was achieved with free 4-OHT at 48 and 72 h post-treatment. Cell proliferation analysis showed that 4-OHT and anti-miR-21 co-loaded NPs significantly inhibited MCF-7 cell growth compared to that of free 4-OHT (1.9-fold) and untreated cells (5.4-fold) at 1 μM concentration. The growth rate of MCF7 cells treated with control NPs or NPs loaded with anti-miR-21 showed no significant difference from that of untreated cells. These findings demonstrate the utility of the PLGA-b-PEG polymer NPs as an effective nanocarrier for co-delivery of anti-miR-21 and 4-OHT as well as the potential of this drug combination for use in the treatment of ER+ breast cancer.

Dataset Information

Improving anti-melanoma effect of curcumin by biodegradable nanoparticles.

Publications

Improving anti-melanoma effect of curcumin by biodegradable nanoparticles.

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