Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 46
·7750-7759
·
IF 4.776
Zhaoming Guo,Kun Zheng,Zhenquan Tan,Ye Liu,Ziyin Zhao,Guang Zhu,Kun Ma,Changhao Cui,Li Wang,Tianyu Kang
The resistance of tumor cells is a major cause of chemotherapy failure in cancer patients. Photodynamic therapy (PDT) as a noninvasive treatment strategy with high specificity is a promising method for the treatment of cancer. In this study, a CD44 and N-cadherin dual targeting drug delivery system in combination with mesoporous titanium dioxide nanoparticle (MTN)-based PDT has been successfully constructed for overcoming drug resistance. Hyaluronic acid (HA) and ADH-1 (a cyclic pentapeptide) were grafted onto the surface of MTN to construct ADH-1-HA-MTN, and doxorubicin (DOX) was selected as a model drug. HA can both trap DOX in the wells of MTN and target CD44-overexpressing tumor cells. ADH-1 blocks the EMT process of tumor cells by selectively inhibiting the function of N-cadherin. Besides, a large number of reactive oxygen species (ROS) were generated by MTN under X-ray irradiation, which could provide a cancer cell killing effect. Cytotoxicity tests showed that ADH-1-HA-MTN/DOX was more toxic to tumor cells than its non-ADH-1 modified counterparts. Western blotting analysis showed that ADH-1-HA-MTN/DOX overcame the drug resistance of tumor cells by preventing the process of epithelial–mesenchymal transition. Taken together, ADH-1-HA-MTN may be a promising targeted drug delivery system to overcome the drug resistance of tumors.
研究领域:
癌症治疗
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-15
·
IF 9.429
Du Bin,Zheng Mei,Ma Huizhen,Huang Jingshu,Jiao Qingqing,Bai Yimeng,Zhao Mengmeng,Zhou Jie
Multidrug resistance is still a major obstacle to cancer treatment. The most studies are to inhibit the activity of the drug transporter P-glycoprotein (P-gp), but the effect is not ideal. Herein, a nanosystem was built based on cascade catalytic consumption of cholesterol. Cholesterol oxidase (natural enzyme, COD) was immobilized on the carrier (NH2-MIL-88B, MOF) through amide reaction, COD catalyzed the consumption of cholesterol, the reaction product H2O2 was further produced by the MOF with its peroxidase-like activity to produce hydroxyl radicals (•OH) with killing effect. Due to the high expression of CD44 receptor on the surface of tumor cells, we encapsulated chondroitin sulfate gel shell (CS-shell) with CD44 targeting and apoptosis promoting effect on the surface of DOX@MOF-COD nanoparticles, which can accurately and efficiently deliver the drugs to the tumor site and improve the effect of reversing drug resistance. Taking drug-resistant cell membrane as "breakthrough", this paper will provide a new idea for reversing multidrug resistance of tumor.Graphical Abstract
研究领域:
纳米技术
·
癌症生物学
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药物科学
·
酶学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Hua Guo,Huimin Wang,Yiyi Zhang,Hong Deng,Ching-Hsuan Tung,Weiqi Zhang
The complex of doxorubicin (Dox) and intracellular iron in cardiomyocytes generates reactive oxygen species (ROS), contributing to commonly observed cardiotoxicity. To enhance the anticancer potency and minimize the cardiotoxicity, here Dox was formulated into a hyaluronan (HA) nanogel using ferric ion (Fe3+) coordination to control the intracellular distribution and release of Dox. Taking advantage of the paramagnetic properties of iron and the fluorescence of Dox, we conveniently monitored the targeted delivery of the HA@Dox nanogel in murine breast tumors through both T1-weighted magnetic resonance imaging and fluorescence imaging. Compared with free Dox, HA@Dox nanogel affords a CD44-targeted delivery, lysosomal distribution, pH-responsive release, and significant tumor inhibition. Mechanistically, the lysosome-enriched HA@Dox produces ROS, causing lysosomal membrane permeabilization, which further promotes the intracellular Dox distribution. This HA@Dox nanogel not only provides a facile cancer-targeted delivery but also successfully relieves Dox toxicity, representing a potent delivery system for Dox.
研究领域:
药理学
·
肿瘤学
·
纳米医学
·
化疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
·
2019
·
IF 4.018
Yong Deng,Shunjie Pan,Jiajun Zheng,Yale Hong,Jie Liu,Haizhou Chang,Yuqing Miao,Yun Sun,Yuhao Li
Photodynamic therapy (PDT) is one of effective cancer therapy methods. It is important to develop a PDT reagent with tumor-targeted ability, high phototoxicity and low dark toxicity. In this study, an iridium(III) complex (Irpy) can electrostatically self-assemble with hyaluronic acid (HA) to form nanostructured Irpy-HA, which exhibited stable spheroid structure and outstanding ability of singlet oxygen ( 1 O 2 ) generation. The photophysical property of Irpy has been well studied, which qualified green light absorption ability and could emit red phosphorescence. The nanostructure and stability of self-assembled Irpy-HA have been well investigated, which can keep its nanostructure at least 30 days. More importantly, Irpy-HA can target to a CD44 receptor in cancer cell membrane for enhancing internalization and selective disintegration. Then, Irpy can accumulate in mitochondria and generate 1 O 2 to realize PDT-induced cell apoptosis by green light irradiation. The Irpy-HA could be used as a nanophotosensitizer for effective photodynamic therapy.
研究领域:
癌症研究
·
材料科学
·
纳米技术
·
光化学
✓ 已验证
DOI
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2022
·
IF 3.784
Xiaomei Wu,Zhumei Wei,Hui Feng,Hongli Chen,Jiaxiu Xie,Yupeng Huang,Mengyao Wang,Chanjuan Yao,Jianchun Huang
Betulinic acid (BA) is a natural pentacyclic triterpenoid with broad-spectrum anticancer activity, which has great development potential as an anti-cancer drug. In this study, a novel hyaluronic acid (HA)-modified BA liposome (BA-L) was developed for use in targeted liver cancer therapy. The size, polymer dispersity index (PDI), zeta potential , and entrapment efficiency were measured. Cell viability, cell migration and clonogenicity, cellular uptake, immunohistochemistry of CD44, and protein expression of ROCK1/IP3/RAS were also investigated. BA, BA-L, and HA-BA-L had no inhibitory effect on the activity of LO2 normal hepatocytes, but they inhibited the proliferation of HepG2 and SMMC-7721 cells in a dose- and time-dependent manner, with HA-BA-L exhibiting the most prominent inhibitory effect. Compared with the BA-L group, the expression of CD44 in HepG2 cells in the HA-BA-L group was decreased. The results of WB showed that BA, BA-L, and HA-BA-L downregulated the expression of ROCK1, IP3, and RAS in HepG2 cells, and the expression level in the HA-BA-L group was significantly decreased. The easily prepared HA-BA-L was demonstrated to be an excellent CD44-mediated intracellular delivery system capable of targeting effects. Further mechanistic research revealed that the inhibition of HA-BA-L on HepG2 cells may be mediated by blocking the ROCK1/IP3/RAS signaling pathways.
研究领域:
药理学
·
肿瘤学
·
生物技术
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Rangrang Fan,Caili Chen,Junshan Hu,Min Mu,Di Chuan,Zhouyun Chen,Gang Guo,Jianguo Xu
Collateral damage to healthy tissue, uneven heat distribution, inflammatory diseases, and tumor metastasis induction hinder the translation of high-temperature photothermal therapy (PTT) from bench to practical clinical applications. In this report, a multifunctional gold nanorod (GNR)-based nanosystem was designed by attaching siRNA against B7-H3 (B7-H3si), glucose oxidase (GOx), and hyaluronic acid (HA) for efficient low-temperature PTT. Herein, GOx can not only exhaust glucose to induce starvation therapy but also reduce the heat shock protein (HSP), realizing the ablation of tumors without damage to healthy tissues. Evidence shows that B7-H3, a type I transmembrane glycoprotein molecule, plays essential roles in growth, metastasis, and drug resistance. By initiating the downregulation of B7-H3 by siRNA, siRNA-GOx/ [email protected] NPs may promote the effectiveness of treatment. By targeting cluster of differentiation 44 (CD44) and depleting B7-H3 and HSPs sequentially, siRNA-GOx/ [email protected] NPs showed 12.9-fold higher lung distribution than siRNA-GOx/GNR NPs. Furthermore, 50% of A549-bearing mice in the siRNA-GOx/GNR NPs group survived over 50 days. Overall, this low-temperature phototherapeutic nanosystem provides an appropriate strategy for eliminating cancer with high treatment effectiveness and minimal systemic toxicity. Statement of significance To realize efficient tumor ablation under mild low-temperature (42–45 ℃) and RNA interference simultaneously, here we developed a multifunctional gold nanorod (GNR)-based nanosystem (siRNA-GOx/ [email protected] NPs). This nanoplatform can significantly inhibit tumor cell proliferation and induce cell apoptosis by downregulation of HSP90α, HSP70, B7-H3, p-AKT, and p-ERK and upregulation of cleaved caspase-9 at mild low-temperature due to its superior tumor homing ability and the combined effect of photothermal effect, glucose deprivation-initiated tumor starvation, and B7-H3 gene silence effect. It is believed that this multifunctional low-temperature photothermal nanosystem with efficient and specific anticancer properties, shows a potential application in clinical tumor treatment.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
分子生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Xiaowei Wang,Wenjun Zhang,Sheng Zeng,Liudi Wang,Bin Wang
Hepatic fibrosis is a common pathological process in chronic liver diseases, characterized by excessive reactive oxygen species (ROS), activated hepatic stellate cells (HSCs), and massive synthesis of extracellular matrix (ECM), which are important factors in the development of liver cirrhosis, liver failure, and liver cancer. During the development of hepatic fibrosis, ECM collagen produced by activated HSCs significantly hinders medication delivery to targeted cells and reduces the efficiency of pharmacological therapy. In this study, we designed a multifunctional hyaluronic acid polymeric nanoparticle (HA@PRB/COL NPs) based on autophagy inhibitor probucol (PRB) and collagenase type I (COL) modification, which could enhance ECM degradation and accurately target HSCs through specificity binding CD44 receptor in hepatic fibrosis therapy. Upon encountering excessive collagen I-deposition formed barrier, HA@PRB/COL NPs performed the nanodrill-like function to effectively degrade pericellular collagen I, leading to greater ECM penetration and prominent HSCs internalization capacity of delivered PRB. In mouse hepatic fibrosis model, HA@PRB/COL NPs were efficiently delivered to HSCs through binding CD44 receptor to achieve efficient accumulation in fibrotic liver. Further, we showed that HA@PRB/COL NPs executed the optimal anti-fibrotic activity by inhibiting autophagy and activation of HSCs. In conclusion, our novel dual-functional co-delivery system with degrading fibrotic ECM collagen and targeting activated HSCs exhibits great potentials in the treatment of hepatic fibrosis in clinic. Statement of significance The excess release of extracellular matrix (ECM) such as collagen in hepatic fibrosis hinders medication delivery and decreases the efficiency of pharmacological drugs. We aimed to develop a nano-delivery carrier system with protein hydrolyzed surfaces and further encapsulated an autophagy inhibitor (PRB) to enhance fibrosis-related ECM degradation-penetration and hepatic stellate cells (HSCs) targeting in hepatic fibrosis niche (HA@PRB/COL NPs). The COL of HA@PRB/COL NPs successfully worked as a scavenger to promote the digestion of the ECM collagen I barrier for deeper penetration into fibroid liver tissue. It also accurately targeted HSCs through specifically binding to the CD44 receptor and subsequently released PRB to inhibit autolysosome and ROS generation, thus preventing HSCs activation. Our HA@PRB/COL NPs system provided a promising therapeutic strategy for hepatic fibrosis in a clinic setting.
研究领域:
药理学
·
纳米技术
·
肝病学
·
细胞生物学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 15
·3453-3472
·
IF 7
Fan Xu,Minghua Li,Zujun Que,Mingliang Su,Wang Yao,Yu Zhang,Bin Luo,Yan Li,Zhanxia Zhang,Jianhui Tian
Combining chemotherapy and immunotherapy is a promising strategy for the treatment of non-small cell lung cancer (NSCLC) metastasis. However, platinum-based chemotherapeutics and immune checkpoint blockade-based cancer immunotherapy have toxic side effects and limitations. Ursolic acid (UA) and astragaloside IV (AS-IV) are natural compounds with anticancer activity sourced from Traditional Chinese medicine (TCM). However, their poor water solubilities and targeted deletions limit their medicinal value. In this study, we fabricated hyaluronic acid (HA)-modified UA/(AS-IV)-loaded polydopamine (PDA) nanomedicine (UA/(AS-IV)@PDA-HA) with a high yield at a low cost via simple synthesis. This represents a novel multifunctional nanomedicine that combines chemotherapy, photothermal therapy (PTT), and immunotherapy with an active tumor-targeting ability. The as-prepared nanomedicine not only increased the aqueous solubilities of UA and AS-IV, but also improved their active targeting abilities. HA binds specifically to the overexpressed cluster of differentiation 44 (CD44) on the surface of most cancer cells, thereby improving drug targeting. While evaluating the anticancer effect of UA/(AS-IV)@PDA-HA in vitro and in vivo, the PDA nanodelivery system significantly improved UA-mediated cytotoxicity and anti-metastatic ability against NSCLC cells. In addition, the system also improved the AS-IV-mediated self-immune response of tumor-related antigens, which further inhibited the growth and distant metastasis of NSCLC. Further, PDA nanomaterial-mediated PTT inhibited tumor growth substantially. UA/(AS-IV)@PDA-HA not only significantly eradicated the primary tumor but also strongly inhibited the distant metastasis of NSCLC in vitro and in vivo. Thus, it has immense potential for development as an efficient anti-metastatic agent for NSCLC.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Xu Enyu,Liu Xinbo,Chen Xuelian,Chen Huimin,Chen Yin,Chen Yan
In this study, hollow mesoporous silica (HMSN) was created to facilitate drug distribution using the hard template method. The oxidized hyaluronic acid (oxiHA) was coated on the carrier surface by the Schiff base reaction, producing the pH-responsive nanoparticles HMSNs-DOX-oxiHA targeted by CD44 and preventing drug leakage from mesopores. The prepared nanoparticles had a size of 151.79 ± 13.52 nm and a surface potential of −8.42 ± 0.48 mV. The rich mesoporous structure and internal cavity of HMSNs-NH 2 achieved the effective encapsulation and loading rates of doxorubicin (DOX) at 76.84 ± 0.24 % and 18.73 ± 0.05 %, respectively. Owing to the pH sensitivity of imine bonds, HMSNs-DOX-oxiHA has a good pH response and release performance. The in vitro experiments showed that the nanoparticles were not cytotoxic and could enhance HCT-116 uptake efficiency by hyaluronic acid/CD44 receptor-mediated endocytosis , effectively inhibiting tumor cell proliferation and reducing toxic side effects on normal cells. In summary, the polysaccharide-based nano-drug delivery system constructed in this experiment not only has the basic response properties of a carrier but also introduces the bioactive advantages of natural polysaccharides.
研究领域:
纳米技术
·
药学
·
生物材料
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Sun Junpeng,Du Jiaqun,Liu Xiaobang,An Jinyu,Hu Yu,Wang Jing,Zhu Fu,Feng Huicong,Cheng Shuai,Tian He,Mei Xifan,Wu Chao
Rheumatoid arthritis (RA) is a chronic autoimmune disease of yet undetermined etiology that is accompanied by significant oxidative stress, inflammatory responses, and damage to joint tissues. In this study, we designed chondroitin sulfate (CS)-modified tragacanth gum–gelatin composite nanocapsules (CS-Cur-TGNCs) loaded with curcumin nanocrystals (Cur-NCs), which rely on the ability of CS to target CD44 to accumulate drugs in inflamed joints. Cur was encapsulated in the form of nanocrystals into tragacanth gum–gelatin composite nanocapsules (TGNCs) by using an inborn microcrystallization method, which produced CS-Cur-TGNCs with a particle size of approximately 80 ± 11.54 nm and a drug loading capacity of 54.18 ± 5.17%. In an in vitro drug release assay, CS-Cur-TGNCs showed MMP-2-responsive properties. During the treatment of RA, CS-Cur-TGNCs significantly inhibited oxidative stress, promoted the polarization of M2-type macrophages to M1-type macrophages, and decreased the expression of inflammatory factors (TNF-α, IL-1β, and IL-6). In addition, it also exerted excellent anti-inflammatory effects, and significantly alleviated the swelling of joints during the treatment of gouty arthritis (GA). Therefore, CS-Cur-TGNCs, as a novel drug delivery system, could lead to new ideas for clinical therapeutic regimens for RA and GA. Graphical Abstract
研究领域:
药剂学
·
免疫学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Teng Liu,Mingyan Yang,Yawen Yu,Xinxin Bai,Yaping He,Fei Yao,Yami Wu,Guangcan Zhou,Yanmei Wang,Dong Qi,Huaying Fan
Acute kidney injury (AKI) is a common clinical syndrome characterized by a rapid decline in kidney function, with inflammation being a key driver. In this study, the hydrophobic drug Rhein was conjugated to hyaluronic acid (HA) via esterification of its carboxyl group. The HA was then modified with 4-hydroxymethylphenylboronic acid pinacol ester (PBAP), which is responsive to reactive oxygen species (ROS). Finally, curcumin was loaded onto this construct to develop a ROS-responsive nanodelivery system (RHP@Cur). In vitro, the nanoparticles showed good ROS responsiveness in H 2 O 2 medium and successfully targeted the CD44 receptors on macrophages. Compared to curcumin alone, RHP@Cur significantly inhibited the secretion of NO and TNF-α and blocked NF-κB activation, with more pronounced effects. RHP itself also exhibited some anti-inflammatory effects. In an in vivo AKI model, the anti-inflammatory effects of RHP@Cur were consistent with the in vitro results. H&E staining results showed that RHP@Cur significantly improved kidney pathological damage. Immunohistochemical results revealed that it reduced the deposition of kidney injury molecule-1 (KIM-1) in the kidneys, with better effects than curcumin and RHP. These results suggest that Rhein exerts a synergistic anti-inflammatory effect, and its potential for combined use with curcumin for kidney therapy makes RHP@Cur more effective than RHP in treating AKI. In addition, since RHP@Cur delivers Cur, it enhances the therapeutic effect of Cur. Therefore, RHP@Cur provides a potential effective means for the treatment of acute kidney injury.
研究领域:
药物纳米技术
·
炎症疾病研究
·
药物递送系统
·
急性肾损伤治疗
·
生物聚合物化学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2024
·
IF 4.4
Kangyuan Hu,Xiuhua Li,Zhaodan Tan,Yan Shi
Ovarian cancer is the most common malignant tumor in women. Shikonin (SHK), an herbal extract from Chinese medicine, shows promise in treating ovarian cancer by inducing reactive oxygen species (ROS). However, its clinical use is limited by poor tumor targeting and low bioavailability, and its therapeutic potential is further compromised by the elevated levels of antioxidants such as glutathione (GSH) within tumor cells. In this study, a novel formulation of ROS-responsive micelles loaded with SHK was developed using hyaluronic acid-phenylboronic acid pinacol ester conjugation (HA-PBAP) for targeted therapy of ovarian cancer through disruption of intracellular redox homeostasis. The SHK@HA-PBAP exhibits targeted delivery to ovarian cancer cells through the interaction between HA and CD44 receptors. Upon internalization by cancer cells, the high levels of intracellular ROS triggered the degradation of SHK@HA-PBAP and simultaneously released SHK and generated GSH scavenger quinone methide (QM). The SHK and QM released from the SHK@HA-PBAP effectively induce the production of ROS and deplete intracellular GSH, leading to the disruption of intracellular redox homeostasis and subsequent induction of cell death. These characteristics collectively inhibit the growth of ovarian cancer. In vitro and in vivo studies have demonstrated that SHK@HA-PBAP micelles exhibit superior antitumor efficacy compared to free SHK in both A2780 cells and A2780 tumor-bearing mice. The ROS-responsive SHK@HA-PBA presents a promising therapeutic approach for the treatment of ovarian cancer.
研究领域:
药学
·
癌症生物学
·
纳米技术
·
药物递送系统
✓ 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）