DRUG DELIVERY
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2019
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IF 3.829
Weijie Li,Ruicong Yan,Yong Liu,Chuanchuan He,Xiaojuan Zhang,Yao Lu,Muhammad Waseem Khan,Chuanrui Xu,Tan Yang,Guangya Xiang
Overexpression of Bmi1 gene is an important feature of cancer stem cell in various human tumors. Therefore, Bmi1 gene can be a potential target for small interfering RNA (siRNA) mediated cancer therapy. Ursolic acid (UA) as a natural product plays a pivotal role in anti-tumor field, although its performance is limited by low bioavailability and poor hydrophilicity. A folate receptor-targeted cationic liposome system was designed for the purpose of investigating the relationship between Bmil siRNA and UA. The folate receptor-targeted cationic liposomes co-delivering UA and Bmi1 siRNA (FA-UA/siRNA-L) were fabricated by electrostatic interaction between folate UA liposome (FA-UA-L) and Bmi1 siRNA. Tumor growth is inhibited by FA-UA/siRNA-L in vitro and in vivo and this inhibition is contributed by a synergistic anti-tumor effect of UA and Bmi1 siRNA. The western blot measurement of apoptosis-protein and cancer stem cell (CSC) marked-protein demonstrated that UA led to activation-induced tumor cell death and Bmi1 siRNA resulted in inhibition of cancer stem cells. Overall, these results indicate that Bmi1 as a regulating gene for cancer stem cell is an effective target for cancer treatment using siRNA and co-delivery of UA and Bmi1 siRNA using folate-targeted liposomes is a promising strategy for improved anti-tumor effect.
研究领域:
肿瘤学
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药学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2021
·
IF 5.268
Ning Wang,Chenyu Liu,Weihe Yao,Hengjun Zhou,Simiao Yu,Hailiang Chen,Weihong Qiao
Constructing highly efficient and multifunctional nanoparticles to overcome the multiple challenges of targeted drug delivery is a new strategy urgently needed in tumor therapy. Here, we synthesized pH-responsive prodrug ( PEG 2K -NH -N- DOX ), GSH-responsive prodrug ( PEG 2K -S-S-CPT ), folate-receptor targeting polymers ( FA-PEG 2K -L8 , FA-PEG 2K -TOS) and T1-enhanced magnetic resonance imaging contrast agents ( Gd-DTPA-N16−16) , used to encapsulate combrestatinA4 (CA4) to prepare multifunctional nanoparticles ( FTDCAG NPs). Unlike other nanoparticles, FTDCAG NPs contains three drugs with the ability to control the release in time and space, which can maximize the effectiveness of precise cancer chemotherapy. We first confirmed that specific binding between FTDCAG NPs and overexpressed folate-receptor cells by flow cytometry and confocal laser scanning microscopy. We then investigated the spatiotemporally controlled release ability of FTDCAG NPs loaded with doxorubicin (DOX), CA4 and camptothecin (CPT). Relative to pH = 7.4, the release efficiency of CA4 in the pH = 6.5 increased by 63.4 %. The first released CA4 is able to destroy the angiogenesis and help tumor cells to be exposed to the remaining FTDCG NPs. After being internalized into the tumor cells, FTDCG NPs is disassembled and the CPT and DOX were released due to the increase of intracellular GSH concentration and the decrease of pH value. Besides, the relaxation time of FTDCAG NPs is 3.86 times that of clinical Gd-DTPA, and the in vitro and vivo T1-weighted imaging is brighter, which can be used to trace the nanoparticles by MRI. Therefore, FTDCAG NPs provide an efficient strategy for the design of multifunctional drug delivery systems for enhancing antitumor efficacy.
研究领域:
纳米医学
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癌症治疗
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Lixin Cheng,Dongmiao Sang,Fangyu Zhao,Lili Yang,Zhilin Guo,Xinfeng Zhang,Qiaoqiao Yang,Wenju Qiao,Xiaohong Sun,Xiaohong Guan,Haoyu Wang,Jiannan Wang,Hongyan Zou,Xiu'e Li,Fang Fang,Yang Li,Shujun Zhang,Lina Wu,Huiming Lin,Xilin Sun,Kai Wang
Developing new nanoplatforms for dynamically and quantitatively visualizing drug accumulation and targeting within tumors is crucial for precision cancer theranostic. However, achieving efficient tumor therapy via synergistic photothermal/photodynamic therapy (PTT/PDT) using a single excitation light source, remains a challenge. In this work, we designed Gd-surface functionalized copper sulfide nanoparticles that were modified with folic acid (FA) (Cu 1.96 [email protected] ) to overcome the above limitations and promote PTT/PDT therapeutics. Here, Cu 1.96 S-Gd nanoparticles were synthesized via a coprecipitation method. All samples exhibited high longitudinal relaxivity (up to 12.9 mM −1 s −1 ) and strong photothermal conversion efficiency (50.6%). Furthermore, the Gd ions promoted electron-hole segregation, inducing the Cu 1.96 S-Gd nanoparticles to generate more reactive oxygen species (ROS) than pure Cu 1.96 S nanoparticles. The Cu 1.96 [email protected] enabled the targeting of folate receptor (FR) and promoted cellular uptake, consequently enhancing oncotherapy efficacy. Compared to non-targeted Cu 1.96 S-Gd, a higher signal enhancement for magnetic resonance (MR) imaging in vivo by Cu 1.96 [email protected] was recorded. Given photothermal ability, the nanoparticles also could be visualized in infrared (IR) imaging. Furthermore, the nanoparticles exhibited biodegradation behavior and achieved good drug elimination performance via renal clearance. Our strategy, integrating Cu 1.96 [email protected] nanoparticles, MR/IR dual-modal imaging, and PTT/PDT into one nanoplatform, demonstrated great potential for anti-breast cancer therapy by effectively targeting FR overexpressed breast cancer cells.
研究领域:
纳米技术
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生物医学工程
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癌症研究
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诊疗学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2023
·Vol. 28
·期 6
·115
·
IF 3.1
Yaqiong Li,Yongqing Chen,Ruiqing Liu,Shaobo Duan,Lijuan Chen,Jun Sun,Lianzhong Zhang
Background: Ultrasound-responsive nanodroplets (NDs) targeting tumors have shown great potential in ultrasound imaging and tumor therapy, but most of these studies are based NDs with lipid shells that cannot overcome the uptake by cells of the reticulo-endothelial system (RES). NDs with shells comprised of polyethylene glycol (PEG)-based polymers could effectively suppressed the uptake of RES, but the phase transition, contrast-enhanced imaging and drug release about these NDs have not been well illuminated. Methods: Folate receptor targeted NDs with shells of polymers and loaded with DOX (FA-NDs/DOX) were prepared. The particle size distribution and morphology of NDs was characterized with dynamic light scattering (DLS) and microscope. Phase transition and contrast-enhanced ultrasound imaging under different mechanical indices (MIs) was studied, and the intensity of contrast enhancement were quantitatively analyzed. The targeting property of FA-NDs/DOX to MDA-MB-231 cells and cellular uptake were observed using a fluorescence microscope. The anti-tumor effects of FA-NDs/DOX combined with low-intensity focused ultrasound (LIFU) was studied through cytotoxicity tests. Flow cytometry assays were used to detect cell apoptosis. Results: The average particle size of the FA-NDs/DOX was 448.0 ± 8.9 nm, and the zeta potential was 30.4 ± 0.3 mV. When exposed to ultrasound at 37 °C, ultrasound contrast enhancement of FA-NDs/DOX was observed when MI ≥0.19. A stronger acoustic signal was observed under higher MIs and concentrations. The results of quantitative analysis showed that the contrast enhancement intensity of FA-NDs/DOX (1.5 mg/mL) at MI of 0.19, 0.29 and 0.48 was 26.6 ± 0.9 dB, 97.0 ± 3.8 dB and 153.1 ± 5.7 dB, respectively. The contrast enhancement of the FA-NDs/DOX lasted for more than 30 minutes at an MI of 0.48. In targeting experiments, FA-NDs could be recognized by MDA-MB-231 cells, and significant cellular uptake was observed. The blank FA-NDs showed good biocompatibility, while the FA-NDs/DOX induced apoptosis of MDA-MB-231 and MCF-7 cells. By combining LIFU irradiation and FA-NDs/DOX treatment, the best cell-killing effect was achieved. Conclusions: The FA-NDs/DOX prepared in this study has excellent performance in contrast-enhanced ultrasound imaging, tumor targeting and enhanced chemotherapy. This FA-NDs/DOX with polymer shells provides a novel platform for ultrasound molecular imaging and tumor therapy.
研究领域:
生物医学工程
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药学
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肿瘤学
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医学影像
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纳米技术
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）