JOURNAL OF CONTROLLED RELEASE
·
2016
·
IF 7.441
Tingjie Yin,Jiyong Liu,Zekai Zhao,Lihui Dong,Han Cai,Lifang Yin,Jianping Zhou,Meirong Huo
Co-delivery systems capable of transporting hydrophobic chemotherapeutics and hydrophilic siRNA to the same cell population with simultaneous burst release of both drugs to maximize synergistic anticancer efficacy remains elusive. In this light, a multifunctional nanoparticle (HA-PSR) consisting of a redox-sensitive core and detachable crosslinked hyaluronic acid (HA) shell was developed. Octyl modified PEI containing disulfide linkages (PSR) were synthesized as the core materials for co-encapsulation of chemotherapeutics and siRNA, while a HAase-sensitive thiolated HA (HA-SH) was collaboratively assembled to the anionic shell for CD44-mediated active targeting along with enhanced and detachable protection for drug loaded inner cores. Resultantly, HA de-protected redox-sensitive inner cores achieved co-burst release of both cargoes when triggered by glutathione (GSH) rich environments in cytoplasm. Results of in-vivo and in-vitro testing indicated successful co-encapsulation of hydrophobic drugs and hydrophilic siRNA with adjustable ratios. Selective delivery to CD44 overexpressing tumors was achieved through passive and active targeting, followed by HAase-triggered HA de-shielding and GSH-triggered burst release of both cargos. Rapid intracellular trafficking maximized synergistic cytotoxicities of chemotherapeutics and siRNA for remarkable tumor inhibition in a xenograft animal tumor model. Consequently, the HA-PSR nanoparticle holds great potential for combined chemotherapeutics/siRNA treatment in cancer with maximized synergistic antitumor efficacy.
研究领域:
纳米技术
·
癌症研究
·
药学科学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF WUHAN UNIVERSITY OF TECHNOLOGY-MATERIALS SCIENCE EDITION
·
2018
·Vol. 33
·期 2
·512-523
·
IF 0.524
Zhou Huimin,Gao Yuxiang,Xu Haixing,Li Xin,Lü Yahui,Ma Tian,Cai Xinjie,Li Rui,Wang Xiaobing,Xu Peihu
A multifunctional drug delivery system (GNRs@mSiO 2 -HA-RGD) was developed by conjugating targeting ligand hyaluronic acid (HA) and RGD with mesoporous silica- coated gold nanorods (GNRs@mSiO 2 ) for dual-targeted chemo-photothermal therapy. The physiochemical properties of the prepared nanoparticles were characterized by FTIR, UV-vis spectra, and 1 H NMR. Doxorubicin hydrochloride (DOX), an anticancer drug, was used as the model drug to investigate the drug loading, in vitro drug release profiles and cytotoxicity. The experimental results show that DOX-GNRs@mSiO 2 -HA-RGD is synthesized with a mean diameter of 116 nm and a sufficient load capacity of about 19.8%. It also has pH-enzyme sensitive and NIRtriggered drug release manner. Cellular uptake indicates that DOX-GNRs@mSiO 2 -HA-RGD exhibits a higher cellular uptake via CD44 receptor and integrin receptor mediated endocytosis compared with the GNRs@ mSiO 2 modified with one receptor or no receptor. In comparison with chemotherapy or photothermal therapy alone, DOX-GNRs@mSiO 2 -HA-RGD displayes the synergistic effects and achieves a higher therapeutic efficacy. It can be expected that DOX-GNRs@mSiO 2 -HA-RGD is a potential dual-targeted chemo-photothermal therapeutic platform for effective cancer treatment.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yun Liu,Ziying Zhang,Yu Xia,Mengnan Ran,Qing Wang,Quanxin Wu,Wenhua Yu,Cao Li,Shiying Li,Ning Guo
In addition to tumor cells, M2-like tumor-associated macrophages (TAMs) also promote tumor progression. Accordingly, the strategy of targeted depletion or repolarization of M2-like TAMs becomes attractive. Here, we report a dual-targeting nanoagent SAMMH to tumor cells and M2-like TAMs for combinatorial tumor treatment. After co-loading the sonosensitizer spafloxacin (SPX) and oxidative phosphorylation inhibitor atavaquone (ATO) into hollow MnO 2 , the addition of Fe 3+ and tannic acid-immobilized hyaluronic acid (HA) caused the formation of SAMMH through generating metal-polyphenol networks (MPNs) coatings outside. In vitro endocytosis assays demonstrated the efficient internalization of SAMMH by both tumor cells and M2-like TAMs through the specific CD44-HA interactions. The GSH-sensitive degradation of SAMMH results in the continuous release of SPX and ATO. Meanwhile, SAMMH could catalyze the endogenous H 2 O 2 to extra O 2 , thus improving the therapeutic effect via the combination of Mn 2+ -induced CDT and O 2 -generation/O 2 -economy dual-enhanced sonodynamic therapy (SDT). Interestingly, SAMMH had a good targeted M2-like TAMs depleting capacity and could promote M2-to-M1 TAMs transformation by CDT-enhanced SDT, leading to a combinational anti-tumor effect. This dual-targeting nanoagent is a promising candidate to achieve CDT-enhanced SDT against both tumor cells and M2-like TAMs, thus providing new insights for the development of highly effective antitumor therapeutics.
研究领域:
癌症治疗
·
纳米医学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Xuejing Zhang,Shiwei Niu,Gareth R. Williams,Jianrong Wu,Xia Chen,Hong Zheng,Li-Min Zhu
In this study, we report a novel pH and temperature responsive paclitaxel-loaded drug delivery system based on chitosan and di(ethylene glycol) methyl ether methacrylate. This was functionalized with hyaluronic acid to permit active targeting of CD44-overexpressing human breast cancer cells. The resultant HA-CS-g-PDEGMA-PTX nanoparticles (NPs) have small and uniform sizes (˜170 nm), a high drug loading (13.6 ± 1.3%) and high encapsulation efficiency (76.2 ± 8.5%). Cell viability and confocal microscopy experiments demonstrated that the NPs could effectively target and kill MDA-MB-231 human breast cancer cells, but were much less toxic to healthy human umbilical vein endothelial cells. In vivo biodistribution studies in mice showed that the NPs accumulated in the tumor site, while free drug was distributed more widely and rapidly cleared from the body. Histopathological studies revealed that the NPs led to enhanced apoptosis in the tumor site, which resulted in reduced tumor growth. The NPs prepared in this work have great potential for the treatment of breast cancers, and further offer a platform with which to target other cancers.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2018
·
IF 5.158
Shulong Jiang,Mengying Li,Ying Hu,Zhenhai Zhang,Huixia Lv
A polymer of Galactosamine-hyaluronic acid-Vitamin E succinate (Gal-HA-VES) was designed to prepare multifunctional self-assembled micelles for delivery of Norcantharidin (NCTD) to Hepatic carcinoma. NCTD/Gal-HA-VES showed higher cytotoxicity toward CD44-overexpressing MCF-7 cells, MCF-7/Adr cells and ASGP-R overexpressing HepG2 cells, consistent with the enhanced cellular uptake in the selected cell models, indicating Gal-HA-VES micelles were taken up in MCF-7 and HepG2 cells by CD44 and ASGPR receptor mediated endocytosis, respectively. Moreover, the accumulation of Rhodamine 123 demonstrated that Gal-HA-VES has the same action of TPGS as a P -glycoprotein inhibitor blocked drug efflux-related MDR mechanism in resistant MCF-7/Adr cells. The Cell apoptosis assays indicated that NCTD/Gal-HA-VES were more effective in triggering apoptosis, compared with free NCTD or NCTD/HA-VES groups. In vivo study demonstrated that NCTD/Gal-HA-VES group exhibited enhanced tumor targeting and antitumor activity with lower systemic toxicity. Hence NCTD/Gal-HA-VES micelles system can achieve significant tumor targeting and effective treatment of hepatic carcinoma.
研究领域:
药学
·
癌症研究
·
生物医学工程
·
分子生物学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 9
·5380-5396
·
IF 6.895
Yalin Sun,Yan Liang,Na Hao,Xiaoheng Fu,Bin He,Shangcong Han,Jie Cao,Qingming Ma,Wen Xu,Yong Sun
9-Nitro-20(S)-camptothecin (9-NC) is a broad-spectrum antitumor drug used in tumor treatments, but its clinical applications and antitumor efficacy are limited by its structural instability, poor solubility, and extremely low drug utilization in tumor tissues. In this study, enzyme-sensitive nuclear-targeted dual-functional polymeric micelles were developed for 9-NC delivery with a high drug loading content (12.93 ± 0.88%), steady-state circulation, and a rapid attack at the “heart” of tumor cells. Briefly, chrysin (CHR) as a π-conjugated moiety was immobilized on the PCL terminal in the TAT–PCL amphiphiles and combined with the ALAL peptide as a linker on HA chains to yield the ultimate CHR–PCL–TAT–ALAL–HA (HATPC) amphiphiles. Spherical 9-NC-loaded micelles were obtained from the self-assembly of the dual-functional amphiphiles comprising HATPC and 9-NC with uniform nanosize (121.6 ± 5.79 nm), well-distributed morphology (PDI: 0.256), and negative surface charge (−23.2 ± 0.5 mV), yielding high stability during blood circulation. In this drug delivery system, HA acts as an active tumor-targeting instrument via CD44-receptor-mediated endocytosis; further, the ALAL peptide could be cutoff in the lysosomes of the tumor cells due to the high expression of cathepsin B, leading to lysosomal escape, while the secondary polymeric micelles targeted the tumor cell nucleus via the exposed TAT peptide. The enzyme sensitivity and nuclei targetability of the 9-NC/HATPC micelles were confirmed by dynamic light scattering and confocal laser scanning microscopy analyses. As compared to free 9-NC and traditional mPEG2k–PCL2k polymeric micelles, 9-NC/HATPC micelles were the most concentrated in the tumor cell nucleus; therefore, they exhibited the highest cytotoxicity against SKOV3 tumor cells both in vitro (IC50 = 0.03 μg mL−1) and in vivo. This enzyme-sensitive nuclear-targeted dual-functional drug delivery system involving HATPC provided a new and promising strategy for enhanced 9-NC delivery and antitumor efficacy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Huiwen Hou,Yan Li,Wen Tang,Didi Gao,Zengmei Liu,Feiyan Zhao,Xinqing Gao,Peixue Ling,Fengshan Wang,Feng Sun,Haining Tan
Blocking the tumor nutrient supply through angiogenic inhibitors is an effective treatment approach for malignant tumors. However, using angiogenic inhibitors alone may not be enough to achieve a significant tumor response. Therefore, we recently designed a universal drug delivery system combining chemotherapy and anti-angiogenic therapy to target tumor cells while minimizing drug-related side effects. This system (termed as PCCE) is composed of biomaterial chondroitin sulfate (CS), the anti-angiogenic peptide ES2, and paclitaxel (PTX), which collectively enhance antitumor properties. Interestingly, the PCCE system is conferred exceptional cell membrane permeability due to inherent characteristics of CS, including CD44 receptor-mediated endocytosis. The PCCE could respond to the acidic and high glutathione conditions, thereby releasing PTX and ES2. PCCE could effectively inhibit the proliferation, migration, and invasion of tumor cells and cause apoptosis, while PCCE can affect the endothelial cells tube formation and exert anti-angiogenic function. Consistently, more potent in vivo antitumor efficacy and non-toxic sides were demonstrated in B16F10 xenograft mouse models. PCCE can achieve excellent antitumor activity via modulating angiogenic and apoptosis-related factors. In summary, we have successfully developed an intelligent and responsive CS-based nanocarrier known as PCCE for delivering various antitumor drugs, offering a promising strategy for treating malignant tumors.
研究领域:
药理学
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纳米技术
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-20
·
IF 12.6
Jiang Tao,Tang Zixiang,Tian Shumiao,Tang Haitian,Jia Zhekun,Li Fangjian,Qiu Chenyue,Deng Lin,Ke Lang,He Pan,Liu Gang,Chu Chengchao,Xiong Yongfu
Sonodynamic therapy (SDT) exhibits clinical potential for deep-tissue tumor treatment due to its deep tissue penetration and spatiotemporal controllability. Its core mechanism relies on ultrasound-activated sonosensitizers to generate reactive oxygen species (ROS), thereby inducing tumor cell apoptosis. However, conventional sonosensitizers face limitations in ROS yield and tumor-targeting efficiency. In this study, we innovatively designed a multifunctional metal–organic nanosheet (TiZrRu-MON) by hydrothermal coordination of [Ru(bpy)₃] 2 ⁺ photosensitizing units with TiZr-O clusters, while incorporating Fe 3 ⁺ to construct a cascade catalytic system. Experimental results demonstrated that: (1) Fe 3 ⁺ lattice doping significantly enhanced charge carrier mobility and ultrasound-triggered 1 O₂ quantum yield via the formation charge transfer channels; (2) The acidic tumor microenvironment activated Fe 3 ⁺-mediated Fenton reactions, establishing a positive feedback loop with SDT to synergistically amplify ROS generation; (3) Hyaluronic acid functionalization improved nanosheet internalization in HepG2 tumor cells through CD44 receptor-mediated endocytosis. Remarkably, ultrasound irradiation induced substantial oxidative stress and immunogenic cell death, promoting the release of damage-associated molecular patterns (DAMPs), which elevated the maturation rate of tumor-infiltrating dendritic cells (DCs) and significantly increased the proportion of CD8⁺ T cells. In a mouse subcutaneous tumor model, the system achieved effective tumor suppression with manageable systemic toxicity. This work proposes a metal–ligand coordination strategy to advance the development of high-performance sonosensitizers and immunomodulatory antitumor technologies. Graphical
研究领域:
纳米医学
·
癌症治疗
·
生物无机化学
·
生物医学工程
·
免疫治疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）