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S180 肿瘤
Journal of Materials Chemistry B · 2015 ·Vol. 4 ·期 4 ·760-767 · IF 4.726

Reverse micelles-in-microspheres with sustained release of water-soluble combretastatin A4 phosphate for S180 tumor treatment

Liping wu,Liyan Qiu

Combretastatin A4 phosphate (CA4P), the water-soluble phosphate pro-drug of combretastatin A4 (CA4), acts as a novel vascular disrupting agent (VDA). It strongly inhibits tubulin polymerization and selectively exerts action against tumor blood vessels. However, its quite short half-life (∼30 min) results in a short action time and consequently limits its application. Therefore, it is beneficial to develop a sustained-release preparation of CA4P for relatively long action duration. On the other hand, conventional PLGA microspheres display poor encapsulation capability for water-soluble small molecules due to rapid diffusion outside. Hence, we developed CA4P-loaded microspheres (CA4P-MS) composed of methoxy poly(ethylene glycol)-b-polylactide (PELA) reverse micelles and PLGA with a nano-in-micro sea-island structure. The CA4P encapsulation efficiency of CA4P-MS reached 92.88%. More interestingly, sustained drug release was achieved, which contributed to the prolonged inhibition effect on S180 tumor during a 30-day period with one-time subcutaneous administration. In conclusion, our study established a biodegradable polymer based platform to construct microspheres for water-soluble small molecular compounds with sustained release and a long-lasting action.

CAS / MDL: 616-38-6 9002-89-5
研究领域: 药剂学 · 肿瘤学 · 生物材料
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE · 2024 ·Vol. 28 ·期 16 ·e70032 · IF 4.3

Lycorine (Lycoris radiata)—a unique natural medicine on breast cancer

Qinbing Xue,Bing Wang,Jie Feng,Chaoyu Li,Miao Yu,Yan Zhao,Zheng Qi

Breast cancer (BC) is one of the most common types of cancer among women worldwide. Lycorine ( Lycoris radiata ), a small molecule derived from the traditional Chinese herb Amaryllidaceae plants, has appeared potential effect on inhibiting the growth of cancer cells and inducing apoptosis in various types of cancer with minor side effects. To discuss the therapeutic effects and molecular mechanisms of lycorine on BC established by lycorine-treated S180 tumour-bearing mice in vivo. Furthermore, both the mitotic and microtubule assembly dynamics genes were performed by qPCR assays, and the protein expression associated with mitotic arrest was investigated by western blot. Lycorine was demonstrated to reduce sarcoma growth of S180 tumour-bearing mice and inhibit the proliferation of MCF-7 cells in concentration-dependent manner. Moreover, lycorine induced M phase cell cycle arrest via interfering with the mitotic apparatus regulated the expression of 20 genes and 15 proteins in cell cycle progression. Furthermore, this study confirmed that the potential effect of lycorine on BC might be mediated by cell cycle arrest in M phase for the first time. These results would be the consequence of exploitation of lycorine as a potential drug for BC therapy, however further preclinical and clinical studies are still needed.

CAS / MDL: 476-28-8
研究领域: 肿瘤学 · 药理学 · 分子生物学 · 中药学
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JOURNAL OF PHARMACEUTICAL SCIENCES · 2017 · IF 2.713

Water-Soluble Combretastatin A4 Phosphate Orally Delivered via Composite Nanoparticles With Improved Inhibition Effect Toward S180 Tumors

Yurun Shen,Liping Wu,Liyan Qiu

Combretastatin A4 phosphate (CA4P) is a novel vascular disrupting agent for cancer therapy. However, frequent dosing and negative patient compliance have been encountered over CA4P by injection administration due to its quite short-term action and acute side effects . Therefore, it is significant to develop an oral formulation of CA4P. We established a novel method to prepare CA4P-loaded nanoparticles (CA4P-NPs) for oral administration by combining methoxy poly(ethylene glycol)-b-polylactide (PELA) and poly( d , l -lactic-co-glycolic acid) (PLGA) polymers. Transport study in vitro was evaluated on Madin-Darby canine kidney cell models, and antitumor effect evaluation in vivo was performed on S180 subcutaneous xenotransplanted tumor models in mice. The highest entrapment efficiency of CA4P-NPs was achieved when the weight ratio of PELA to PLGA was optimized to 1:1. The apparent permeability coefficient of CA4P-NPs was found to be 2.08-fold higher than that of free CA4P in transport study. CA4P-NPs reached an absolute bioavailability of 77.6% with the tumor inhibition ratio of 41.2% that was significantly superior to free CA4P. These results suggest a promising application of this composite nanoparticle for the oral delivery of water-soluble drugs.

CAS / MDL: 631-61-8 9002-89-5
研究领域: 药学 · 纳米技术 · 癌症研究 · 药物递送系统
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Journal of Materials Chemistry B · 2016 ·Vol. 4 ·期 11 ·2038-2050 · IF 4.872

Multimodal imaging-guided, dual-targeted photothermal therapy for cancer

Bin Du,Xiaohui Cao,Feifei Zhao,Xiangjie Su,Yuhui Wang,Xiaosa Yan,Shaona Jia,Jie Zhou,Hanchun Yao

The ability to selectively destroy cancer cells while sparing normal tissue is highly desirable during cancer therapy. Herein, dual-targeted photothermal therapy was achieved by the integration of upconversion nanoparticles, Fe3O4 nanoparticles (IONPs), Prussian blue nanoparticles (PBNPs) and hyaluronic acid (HA). PBNPs converted near-infrared (NIR) light into heat and HA/Fe3O4 NPs served as dual-targeting moieties. The as-obtained nanocomposites could also be applied as a multimodal probe for upconversion luminescence (UCL) imaging, enhanced T2-weighted magnetic resonance (MR) imaging and photoacoustic tomography (PAT) imaging. This multifunctional nanoparticle (MFNP) system prepared by a layer-by-layer (LBL) assembly method exhibited excellent dispersivity and low toxicity in vitro and in vivo. Furthermore, the research provided effective results for dual-targeted photothermal ablation of cancer with ∼4 fold higher tumor accumulation than that in the absence of HA/magnetic field. The photothermal therapeutic efficacy has been greatly improved in the S180 tumor model. We present a strategy for multimodal imaging-guided, dual-targeted physical cancer therapy and highlight the promise of using multifunctional nanostructures for cancer theranostics.

研究领域: 癌症治疗 · 纳米医学 · 生物医学工程 · 材料科学
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