BIOMATERIALS
·
2012
·
IF 7.404
Zhaowei Chen,Zhenhua Li,Youhui Lin,Meili Yin,Jinsong Ren,Xiaogang Qu
Recent insight into the molecular mechanisms of natural biomineralization has enabled biomimetic synthesis of functional organic-inorganic hybrid materials under mild reaction conditions. Here, we describe a novel method to construct organic-inorganic hybrid on mesoporous silica nanoparticles by utilizing electrostatically absorbed hyaluronic acid (HA) as a reaction site for deposition of calcium phosphate (CaP) minerals. The addition of another layer of HA on the CaP surfaces not only stabilizes the nanocomposites but also confers target ability toward CD44 overexpressed cancer cells. The nanomaterials enable controlled release of loaded anticancer drugs in acidic subcellular environments after receptor mediated endocytosis . More importantly, our study demonstrated that the cancer targeting nanomaterials dramatically enhanced cellular uptake and cytotoxicity toward breast carcinoma cells. These results thus open new opportunities for biomineralization guided nanostructure assemblies with great potential for biomedical applications .
研究领域:
材料科学
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纳米技术
·
生物医学工程
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-19
·
IF 10.2
Zhang Peisen,Cui Yingying,Wang Jian,Cheng Junwei,Zhu Lichong,Liu Chuang,Yue Saisai,Pang Runxin,Guan Jiaoqiong,Xie Bixia,Zhang Ni,Qin Meng,Jing Lihong,Hou Yi,Lan Yue
Background Although the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects.Results Herein, a novel pH/Hyaluronidase (HAase) dual-stimuli triggered smart nanoprobe FeIIITA@HA has been designed through the biomineralization of Fe3+ and polyphenol tannic acid (TA) under the control of hyaluronic acid (HA) matrix. With the HA residues on the outer surface, FeIIITA@HA nanoprobes can specifically target the SCC cells through the over-expressed CD44, and accumulate in the carcinoma region after intravenously administration. The abundant HAase in carcinoma microenvironment will trigger the degradation of HA molecules, thereby exposing the FeIIITA complex. After ingesting by tumor cells via CD44 mediated endocytosis, the acidic lysosomal condition will further trigger the protonation of TA molecules, finally leading to the Fe3+ release of nanoprobe, and inducing a hybrid ferroptosis/apoptosis of tumor cells through peroxidase activity and glutathione depletion. In addition, Owing to the outstanding T1 magnetic resonance imaging (MRI) performance and phototermal conversion efficiency of nanoprobes, the MRI-guided photothermal therapy (PTT) can be also combined to complement the Fe3+-induced cancer therapy. Meanwhile, it was also found that the nanoprobes can promote the recruitment of CD4+ and CD8+ T cells to inhibit the tumor growth through the cytokines secretion. In addition, the FeIIITA@HA nanoprobes can be eliminated from the body and no obvious adverse side effect can be found in histological analysis, which confirmed the biosafety of them.Conclusion The current FeIIITA@HA nanoprobe has huge potential in clinical translation in the field of precise diagnosis and intelligent synergistic therapy of superficial SCC. This strategy will promisingly avoid the surgical defects, and reduce the systemic side effect of traditional chemotherapy, paving a new way for the future SCC treatment.Graphical Abstract
研究领域:
纳米技术
·
癌症治疗
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生物医学工程
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Ying Zhang,Ruirui Ma,Cuiyu You,Xue Leng,Danyang Wang,Shujing Deng,Binyang He,Ziyang Guo,Zelin Guan,Hengyu Lei,Jie Yu,Qinyuan Zhou,Jianfeng Xing,Yalin Dong
Based on the biocompatibility and macrophage targeting of natural polysaccharides , combined with the physiological and pathological characteristics of the gastrointestinal tract and colonic mucosa of ulcerative colitis (UC), we prepare dexamethasone (Dex)-loaded oral colon-targeted nano-in-micro drug delivery systems coated with multilayers of chitosan (CS), hyaluronic acid (HA), and finally Eudragit S100 (ECHCD MPs) using a layer-by-layer coating technique for UC treatment through regulating the M1/M2 polarization of intestinal macrophages. HA/CS/Dex nanoparticles (HCD NPs) are ingested by macrophages via CD44 receptor-mediated endocytosis to regulate M1-to-M2 macrophage polarization and exert anti-inflammatory effects. Moreover, ECHCD MPs show better colon-targeting properties than Dex-loaded chitosan nanoparticles (CD NPs) and HCD NPs which is demonstrated by stronger mucoadhesion to inflamed colon tissues. After oral administration, ECHCD MPs exert significant anti-UC effects. Therefore, ECHCD MPs are proven to be as promising oral colon-targeting drug delivery systems for Dex and have potential application in UC treatment.
研究领域:
药学
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药物递送系统
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炎症
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胃肠病学
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巨噬细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2017
·
IF 6.402
Wei Chen,Lin Li,Xiaofen Zhang,Yuan Liang,Zhijun Pu,Lingfeng Wang,Jingxin Mo
Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease with no approved targeted therapy. Curcumin has shown therapeutic potential against TNBC, but it shows low bioavailability and low efficacy when administered as a free drug. Here we describe a novel vehicle for in vivo delivery of curcumin based on the phosphorylated calixarene POCA4C6. Curcumin-loaded POCA4C6 micelles (CPM) were prepared using the thin-film method and they showed a unilamellar structure with an average particle size of 3.86 nm. The micelles showed high curcumin encapsulation efficiency and loading was based on liquid chromatography-tandem mass spectrometry. Studies with cell cultures suggest that CPM can sustainably release curcumin in a pH-dependent manner. The micelles efficiently inhibited proliferation, invasion, migration and tumor spheroid formation by BT-549 human breast cancer cells. These effects involved increased apoptosis and reduced levels of nuclear β-catenin and androgen receptor. After injection into tumor xenografts, CPM persisted in the tumor tissue and efficiently inhibited tumor growth without causing obvious systemic toxicity. CPM also significantly reduced levels of CD44+/CD133+ breast cancer stem cells. Our results highlight the potential of CPM as an effective therapy against TNBC.
研究领域:
肿瘤学
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药剂学
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药物递送系统
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癌症干细胞
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Qiuxing Liu,Xin Ding,Xiaoyu Xu,Hualu Lai,Zishan Zeng,Ting Shan,Tao Zhang,Meixu Chen,Yanjuan Huang,Zeqian Huang,Xiuling Dai,Meng Xia,Shengmiao Cui
Tumor cells with innate oxidative stress are more susceptible to exogenous ROS-mediated oxidative damage than normal cells. However, the generated ROS could be scavenged by the overexpressed GSH in cancer cells, thus causing greatly restricted efficiency of ROS-mediated antitumor therapy. Herein, using cinnamaldehyde (CA) as a ROS generator while β-phenethyl isothiocyanate (PEITC) as a GSH scavenger, we designed a tumor-targeted oxidative stress nanoamplifier to elevate intracellular ROS level and synchronously suppress antioxidant systems, for thorough redox imbalance and effective tumor cells killing. First, an amphiphilic acid-sensitive cinnamaldehyde-modified hyaluronic acid conjugates (HA-CA) were synthesized, which could self-assemble into nano-assembly in aqueous media via strong hydrophobic interaction and π-π stacking. Then, aromatic PEITC was appropriately encapsulated into HA-CA nano-assembly to obtain HA-CA/PEITC nanoparticles. Through enhanced permeability retention (EPR) effect and specific CD44 receptor-mediated endocytosis, HA-CA/PEITC nanoparticles could accumulate in tumor tissues and successfully release CA and PEITC under acidic lysosomal environment. Both in vitro and in vivo results showed that the nanoparticles could efficiently boost oxidative stress of tumor cells via generating ROS and depleting GSH, and finally achieve superior antitumor efficacy. This nanoamplifier with good biosafety provides a potential strategy to augment ROS generation and suppress GSH for enhanced oxidation therapy.
研究领域:
纳米技术
·
药学
·
肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Jun Hou,Yanbao Zhao,Lei Sun,Xueyan Zou
Hyaluronic acid (HA) is a naturally polysaccharide that has been used for drug delivery, but is limited by low drug loading capacity and drug leakage in circulation. To improve drug delivery efficient, HA modified porous silica (pSiO 2 ) nanocarriers were successfully prepared for drug delivery and combining therapy. pSiO 2 nanocarriers have stable porous structure and high loading capacity, and pSiO 2 /HA nanocarriers would possess advantages of HA-based carriers and pSiO 2 nanoparticles . Herein, pSiO 2 nanocarriers were prepared by two-phase process, followed by embedding Ag 2 S QDs in the pore walls of pSiO 2 carriers, which render the carriers photothermal effect. pSiO 2 nanocarriers have size of 30 nm, large channels, and high loading capacity (29.3 %). To graft HA, a sensitive linker with alkyl amine and disulfide bond was conjugated on the surface of Ag 2 S/pSiO 2 nanocarriers by three-step reaction. After loading doxorubicin (DOX), HA was grafted via sensitive linker onto the surface of Ag 2 S/pSiO 2 carriers via the formation of amide bonds to seal the loaded drugs. The interaction between HA and CD44 confers the carrier targeting ability to cancer cells. HA coating can be degraded by hyaluronidase resulting in the release of internal cargo. The Ag 2 S/pSiO 2 /HA nanocarriers performs responsive drug release and combining photothermal chemotherapy.
研究领域:
纳米技术
·
生物医学工程
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药学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Panpan Song,Zhongxia Lu,Tianze Jiang,Wenwei Han,Xiangyan Chen,Xia Zhao
The complex tumor microenvironment (TME) makes it difficult for single chemotherapy to achieve satisfactory therapeutic effects. Here, chitosan-coated hyaluronic acid micelles (R/C/ [email protected] ) that co-delivers doxorubicin (DOX) and programmed death-ligand 1 small interfering RNA (siPD-L1) are developed to enhance anti-tumor effect by combination of immunotherapy and chemotherapy. The pH/reduction dual-responsive co-delivery micelles R/C/ [email protected] are spherical particles about 180 nm, and have good drug loading performance, stability, biocompatibility, and TME-responsive drug release properties. The CD44 receptor targeting HA significantly enhances the cellular uptake of DOX and siPD-L1, and siPD-L1 causes the immune infiltration of CD4 + /CD8 + T cells by silencing PD-L1 expression. In vivo studies show that R/C/ [email protected] exhibits significantly stronger anti-breast cancer effect than that of free DOX and micelles loaded only DOX. Therefore, the dual-stimulus responsive micelles provide a promising strategy for combining chemotherapy and siRNA-based immunotherapy to enhance efficacy.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Yilin Wang,Wenting Cheng,Yang Chen,Hailong Tian,Canhua Huang,Ka Li
Cancer stemness in colorectal cancer (CRC) drives immune evasion and fosters an immunosuppressive tumor microenvironment (TME), limiting the efficacy of immunotherapy. To counteract this stemness-driven immune evasion, we developed a hyaluronic acid (HA) surface-modified dual-targeting nanoplatform (HA/pCe6-Ato NPs) that induces both endoplasmic reticulum stress and mitochondrial dysfunction. HA functionalization facilitates tumor-specific targeting via CD44 receptor-mediated endocytosis. The nanoplatform incorporates an ER-targeting photosensitizer, pCe6, synthesized by conjugating Chlorin e6 with p-Toluenesulfonamide, and the mitochondrial respiratory chain inhibitor atovaquone (Ato), which self-assembles into nanoparticles. Upon activation, HA/pCe6-Ato NPs induce ER stress and mitochondrial dysfunction, disrupting cancer stemness and reprogramming the immunosuppressive TME. Preclinical evaluations showed that HA/pCe6-Ato NPs promote apoptosis and accelerate reactive oxygen species production in cancer stem-like cells (CSCs), while reducing immunosuppressive factor secretion and enhancing immune effector cell infiltration. These effects synergistically enhance the efficacy of immunotherapy, achieving superior tumor inhibition compared with conventional monotherapies. Collectively, HA/pCe6-Ato NPs highlight the potential of organelle-targeting strategies to dismantle cancer resilience mechanisms, providing a foundation for dual-targeting nanomedicines to overcome resistance and enhance immunotherapy in CRC.
研究领域:
纳米医学
·
癌症免疫治疗
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分子靶向治疗
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肿瘤生物学
·
活性氧信号通路
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-18
·
IF 10.6
Huai Manxiu,Pei Mingliang,Chen Jie,Duan Xiaoyan,Zhu Yun,Yang Fan,Ge Wensong
The damnification of mitochondrion is often considered to be an important culprit of inflammatory bowel disease (IBD), however, there are fewer reports of mechanisms of mitochondria-mediated IBD treatment. Therefore, we first proposed to reboot mitochondrial energy metabolism to treat IBD by capturing the double-sided factor of ROS and creatine (Cr)-assisted energy adjustment. Herein, an oral Cr-modified selenium-based hyaluronic acid (HA) nanogel (HASe-Cr nanogel) was fabricated for treatment of IBD, through ROS elimination and energy metabolism upgradation. More concretely, due to IBD lesion-specific positive charge and the high expression of CD44, HASe-Cr nanogel exhibited dual targeted inflammatory bio-functions, and ROS-driven degradation properties in high-yield ROS levels in inflammation areas. As expected, multifunctional HASe-Cr nanogel could effectively ameliorate IBD-related symptoms, such as mitochondrial biological function restoration, inhibition of M1-like macrophage polarization, gut mucosal reconstruction, microbial ecological repair, etc., thus excellently treating IBD. Overall, the proposed strategy underlined that the great potentiality of HASe-Cr nanogel by restarting mitochondrial metabolic energy in colitis lesions, providing new a pavement of mitochondrion-mediated colitis treatment in clinical applications.
研究领域:
药学
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纳米技术
·
胃肠病学
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线粒体生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Xiaoxia Yang,Pengfei Shang,Jianbo Ji,Christina Malichewe,Zhiyin Yao,Jing Liao,Dandan Du,Chao Sun,Lei Wang,Ya-jie Tang,Xiuli Guo
In this study, a chitosan-based, self-assembled nanosystem that codelivered microRNA34a (miR34a) and doxorubicin (Dox) with hyaluronic acid (HA) modification (named CCmDH NPs) was developed to reverse the resistance of breast cancer (BCa) cells to Dox. The CCmDH NPs had a diameter of 180 ± 8.3 nm and a ζ potential of 16.5 mV with a slow-release effect for 96 h. The codelivery system could protect miR34a from nuclease and serum degradation and transport miR34a and Dox into drug-resistant MCF-7/A cells. In addition, the CCmDH NPs could inhibit proliferation and promote apoptosis by regulating the protein expression of B-cell lymphoma-2 (Bcl-2) and poly(ADP-ribose) polymerase (PARP) and inhibit invasion, metastasis, and adhesion by regulating E-cadherin, N-cadherin, MMP2, CD44, and Snail molecules. The CCmDH NPs induced a 73.7% tumor reduction in xenograft tumor growth in nude mice in vivo. This study provides evidence for the anticancer activity of CCmDH NPs carrying Dox and miR34a in BCa, especially metastatic Dox-resistant BCa models.
研究领域:
药学
·
癌症研究
·
纳米技术
·
分子生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
·
2022
·
IF 6.814
Feng Ouyang,Xiaoli Zhang,Li Zhang,Yu Liu,Qi Shuai
The treatment efficacy of anticancer drugs in complex physiological environments is still restricted by multi-drug resistance. To overcome this issue, a nanodrug system of HA-SS@CuS@ZIF-8@TPZ&TBMACN (HSCZTT) that breaks through the detoxification barrier for tirapazamine (TPZ) delivery was developed in this manuscript. In addition to the photothermal effect aroused by CuS in HSCZTT, which can damage tumour cells, TBMACN with photostable fluorescence in the aggregate state can also generate sufficient reactive oxygen species (ROS) to destroy tumour cells. The continuous consumption of oxygen in PDT aggravates the hypoxic environment of tumours, which further activates the TPZ released in the acidic microenvironment of the tumour to achieve apoptosis of the tumour cells. The HSCZTT can not only target the CD44 receptor overexpressed on the surface of the cancer cell , but can also effectively consume a large amount of glutathione (GSH) through the disulphide bond-modified hyaluronic acid, which serves as a targeted disulphide bond, interfering with the detoxification barrier. Our finding presents a rational strategy to overcome multidrug resistance for the improved efficacy of anticancer drugs by the targeting of Hyaluronic acid (HA), release of the drug by the acid response of ZIF-8, breakthrough of the detoxification barrier, precise positioning of the drug release and combined treatment with phototherapy and hypoxia-activated chemotherapy.
研究领域:
癌症治疗
·
纳米医学
·
药物科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Ruijie Chen,Xinlu Lin,Qian Wang,Xingsi An,Xinyu Zhao,Yujie Lin,Tuyue Sun,Chenyang Yan,Aimin Cai,Weilan Cao,Youting Zhang,Qing Yao,Longfa Kou
Ulcerative colitis (UC) is a chronic recurrent disease of the gastrointestinal tract. Though the exact etiology is still unknown, inflamed enterocytes, activated macrophages, and the crosstalk between them have been widely believed to play vital roles in the UC progression. Therefore, simultaneously modulating both injured intestinal epithelial cells and activated immune cells could effectively normalize the intestinal microenvironment by regulating cell-specific activities and breaking the vicious loop between them. Herein, we designed a PepT1 and CD44 dual-targeted celecoxib nanoparticle ( [email protected] ) that could selectively deliver celecoxib to both the inflamed enterocytes and the activated M1 macrophages for UC treatment. [email protected] exhibited excellent cell-specific targeting ability to both inflamed epitheliums and M1 macrophages. In vitro studies showed that [email protected] could exert an enhanced anti-inflammatory effect and improve the colonic inflammatory microenvironment via directly modulating Nrf2/HO-1 and NF-κB pathways in epithelial cells and promoting M1 to M2 macrophage polarization. In a DSS-induced mice model, [email protected] significantly attenuated bodyweight loss, reduced colon length shortening, lowered the disease activity index score and alleviated colon histological damage. In addition, [email protected] could also regulate the intestinal flora in UC mice toward a healthier state with improved species uniformity and abundance as well as restored species diversity. Notably, both in vivo and in vitro data proved that [email protected] had more robust therapeutic activity than both Cel solution and single targeted nanoparticle. This study provides a potential strategy for UC drug delivery and effective treatment.
研究领域:
药学
·
生物医学工程
·
免疫学
·
胃肠病学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）