Nanoscale Advances
·
2021
·Vol. 3
·期 23
·6669-6677
·
IF 4.553
Xinran Sun,Kaixiu Chen,Yingyan Liu,Guoda Zhang,Min Shi,Pengfei Shi,Shusheng Zhang
Photodynamic therapy (PDT) has been rapidly developed as an effective therapeutic approach in clinical settings. However, hypoxia seriously limits the effectiveness of PDT. Here, we report a porphyrin-based metal–organic framework combined with hyaluronate-modified CaO2 nanoparticles (PCN-224-CaO2-HA) to target and enhance PDT efficacy. CaO2 reacts with H2O or weak acid to produce O2, overcoming the hypoxia problem. Hyaluronate protects CaO2 and specifically targets the CD44 receptor, which is highly expressed on tumor cell membranes, performing targeted therapy. After PDT treatment in vitro, the survival rates of 4T1 and MCF-7 tumor cells were 14.58% and 22.45%, respectively. The fluorescence imaging showed that PCN-224-CaO2-HA effectively aggregated in the tumor after 12 h of its intravenous injection into tumor-bearing mice. PCN-224-CaO2-HA exhibited efficacious tumor growth inhibition via enhanced PDT. Overall, this nanosystem providing in situ oxygen production was successfully used for targeted PDT with a significantly enhanced therapeutic efficacy in vitro and in vivo.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Fangzhou He,Conghua Xie,Xiaojuan Xu
Breast cancer is one of the most threatening cancers that poses a great risk to women's health . The anti-tumor drug doxorubicin (DOX) is one of commonly used drugs in the treatment of breast cancer. However, the cytotoxicity of DOX has always been an urgent challenge to be solved. In this study, we report an alternative drug delivery system delivering DOX for reducing its physiological toxicity by using the yeast β-glucan particle (YGP) with a hollow and porous vesicle structure. Briefly, amino groups were grafted onto the surface of YGP with the silane coupling agent, then the oxidized hyaluronic acid (OHA) was attached by Schiff base reaction to get HA-modified YGP ( [email protected] =C-HA), finally DOX was encapsulated into [email protected] =C-HA to get DOX-loaded [email protected] =C-HA ( [email protected] =C-HA/DOX). In vitro release experiments exhibited the pH-responsive DOX release from [email protected] =C-HA/DOX. Cell experiments displayed that [email protected] =C-HA/DOX had good killing effect on both MCF-7 and 4T1 cells and could be internalized into these cells through CD44 receptors, showing targetability to cancer cells. Furthermore, [email protected] =C-HA/DOX could effectively inhibit tumor growth and reduce the physiological toxicity of DOX. Thus, the YGP-based vesicle provides an alternative strategy for lowering the physiological toxicity of DOX in the medical treatment of breast cancer.
研究领域:
药学
·
生物医学工程
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ELECTROCHIMICA ACTA
·
2018
·
IF 5.116
Jing Zhao,Yingying Tang,Ya Cao,Tianshu Chen,Xiaoxia Chen,Xiaoxia Mao,Yongmei Yin,Guifang Chen
Cancer stem cells (CSCs) are recognized as an important source of cancers. Surface biomarkers play a critical role for CSCs profiling and also for diagnostic purposes. In this paper, we propose self-assembled supramolecular nanocomposites assisted multiple signal amplification strategy, and successfully apply it in electrochemical detection of an important CSCs biomarker CD44 as well as identification of breast CSCs. A supermolecular composite, consisting of a binding peptide that is able to bind to the target CD44 and a self-assembled diphenylalanine (FF) nanostructure that provides a template for deposition of gold nanoparticles (AuNPs), is elaborately constructed on the surface of an electrode through the linkage of cucurbit[8]urils. In the presence of CD44, this supramolecule is able to provide amplified electrochemical signals from silver-enhancement on AuNPs after target-protection from trypsin-catalyzed digestion. Whereas in the absence of the target, this supramolecular architecture is destroyed, resulting in suppressed signals. Linear sweep voltammetry results present a satisfactory specificity and sensitivity, which also demonstrate a wide linear range with a limit of detection of 2.17 pg/mL toward CD44 protein and a limit of detection of 8 cells/mL toward CD44-positive cancer cells. Therefore, this work provides a promising prospective for further clinic application in the future.
研究领域:
生物技术
·
纳米技术
·
电化学
·
癌症生物学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2022
·Vol. 12
·期 23
·14707-14715
·
IF 4.036
Hongbing Yang,Zhenyan Yu,Shuaishuai Ji,Jie Yan,Lei Han,Yang Liu,Yanjuan Wang,Yimin Niu,Qiang Huo,Ming Xu
Tumor bone metastasis is an important cause of tumor recurrence and death. Although bone-targeting nanoparticles decorated with targeting ligands have shown good affinity for bone tissues with the properties of adhesion to the bone matrix, it is not easy to detach from the surface of the bone matrix in the tumor-bone microenvironment, attributed to the robust coordination force between the targeting ligands, such as bisphosphates with bone-deposited calcium. This may hinder the transport of nanoparticles from bone tissue to bone metastatic tumors. In this research, we designed a bone-targeting nanocarrier with detachable bone-targeting character for the therapy of bone metastases. The nanoparticles were constructed by using ZIF-8 and bone-targeting and MMP enzyme sensitive polypeptide-modified hyaluronic acid as a carrier and proteasome inhibitor Bortezomib (BTZ) as cargo. The results show that the constructed D8-M3-HA-ZIF8@BTZ nanoparticles possessed several favorable properties such as good colloidal stability, acid-sensitive drug release, D8 peptide mediated bone targeting and MMP enzyme-responsive desorption. Besides, nanoparticle endocytosis and cytotoxicity were enhanced through HA-mediated targeting to CD44 over-expressing tumor cells. Altogether, this study provides a potential cascade targeting strategy for improving the delivery effects of bone targeted nanoparticles for the delivery of proteasome inhibitors.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Meng-Wen Ma,Kai-Lin He,Chao-Qing Li,Xiao-Ting Xie,Sui Zhou,Bin Zhang,Xiao-Lin Hou,Cheng Li,Yuan-Di Zhao,Ling-Li Dong,Bo Liu
Rheumatoid arthritis (RA) is an autoimmune disease, in which inflammatory macrophages play a crucial role by secreting a large number of proinflammatory factors to aggravate inflammatory response. In addition, reactive oxygen species (ROS) are abundant in hypoxic joints, inducing chondrocyte apoptosis and causing irreversible bone destruction. In this work, we synthesized hyaluronic acid-modified platinum-tellurium nanorods (HPT) as a photothermal agent to target RA joints, ablating inflammatory macrophages and scavenging ROS in the microenvironment. Hyaluronic acid can specifically bind to the CD44 receptors, which are over-expressed on the surface of inflammatory macrophages, achieving active targeting and improving therapy effectiveness. Under the irradiation of an 808 nm laser, thermal energy produced by HPT, which has high photothermal conversion efficiency is sufficient to induce apoptosis of inflammatory macrophages. Simultaneously, platinum particles on the surface of tellurium nanorods can effectively remove a variety of ROS, reducing oxidative stress and alleviating inflammatory response in RA joints. Collagen-induced arthritis (CIA) mice had been used to study the therapeutic potential of HPT. The results revealed that the clinical scores in CIA mice injected with HPT and irradiated with a near-infrared laser were significantly reduced. The inflammatory response was also obviously relieved, when compared with CIA mice injected with PBS. Micro-CT imaging revealed that bone erosion was visibly reduced in the HPT + Laser group. These results demonstrate that multifunctional HPT is promising to serve as a therapeutic platform for the treatment of RA.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
免疫学
·
风湿病学
✓ 已验证
产品关联
DOI
高影响因子
Cancer Nanotechnology
·
2023
·Vol. 14
·期 1
·1-20
·
IF 5.7
Sharifi Majid,Kheradmandi Rasoul,Alizadeh Morteza
For the treatment of triple-negative breast cancer (TNBC), without expression of estrogen, progesterone and HER2 receptors, specific treatment guideline is still under criticism, especially in tumor hypoxia. But assuming the molecular similarity of TNBC with breast cancer gene-1-related cancers, gemcitabine may be used in TNBC treatment on the nanozyme platform combined with photodynamic therapy (PDT). After designing the nanozyme with four components, platinum–cobalt: with catalase/peroxidase capabilities, hyaluronic acid: nanozyme targeting by interacting with CD44 receptor, poly[ethylene glycol]: water-soluble macromolecule for immune escape, and Gem: antitumor drug, its physicochemical properties was investigated by thermogravimetric, X-ray diffraction and energy dispersive X-ray, and therapeutic effects in in vitro and in vivo. The results show that platinum–cobalt@gemcitabine-hyaluronic acid-polyethylene glycol (PtCo@Gem-HA-PEG) especially synergized with PDT has high toxicity on 4T1 cells and tumor by enhancing the catalase-/peroxidase-like activities to produce O2, O2•− and •OH, and increase the intracellular free radicals. PtCo@Gem-HA-PEG inhibits tumor development by increasing drug accumulation in the tumor and enhancing apoptotic mechanisms through synergistic activity with PDT. Nevertheless, the major organ damage confirmed by the histological method in the long-term application of PtCo@Gem-HA-PEG, makes their application challenging due to permanent catalytic activity. However, results of improved drug permeability based on reduced hypoxia, higher drug retention, and enzyme-like activity that could be synergized with other therapeutic approaches like a PDT, have made their use attractive. Hence, this study provides a promising path in the TNBC treatment by nanozymes, which requires further toxicological investigations.Graphic Abstract
研究领域:
肿瘤学
·
纳米技术
·
药学
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Jiao Sun,Min Li,Kexin Lin,Zhanbiao Liu,Zhe Wang,Wei Wang,Yinan Zhao,Yuhong Zhen,Shubiao Zhang
Quercetin (QT) is a very effective anticancer drug in combating breast cancer. However, it has several disadvantages such as poor water solubility, low bioavailability and low targeting, which seriously restrict its clinical application. In this work, amphiphilic hyaluronic acid polymers (dHAD) were synthesized by grafting dodecylamine to hyaluronic acid (HA). The dHAD self-assembles with QT to form drug-carrying micelles (dHAD-QT). The dHAD-QT micelles possessed excellent drug-loading capacities (75.9 %) for QT and showed significantly improved CD44 targeting compared with unmodified HA. dHAD-QT micelles exhibited high cytotoxicity and apoptosis-inducing abilities, which were ascribed to the pH-sensitive dHAD-QT micelles accomplishing rapid drug release of QT under low pH condition. Importantly, in vivo experiments showed that dHAD-QT effectively inhibited tumor growth in tumor-bearing mice, with a tumor inhibition rate of 91.8 %. Furthermore, dHAD-QT prolonged the survival time of tumor-bearing mice and reduced the toxicity of the drug to normal tissues. These findings indicate that the designed dHAD-QT micelles have promising potential as efficient nano-drugs for breast cancer treatment.
研究领域:
药学
·
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
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yundi Wu,Xudong Liu,Can Yao,Jianqiang Chen,Xilong Wu,Mingqiang Zhu
Autophagy is a process that eliminates damaged cells and malfunctioning organelles via lysosomes, which is closely linked to cancer. Primaquine (PQ) was reported to impede autophagy flow by preventing autophagosomes from fusing with lysosomes at the late stage of autophagy. It will lead to cellular metabolic collapse and programmed cell death. Excessive or extended autophagy enhances the efficacy of chemotherapeutic drugs in cancer prevention. The utilization of autophagy inhibition in conjunction with chemotherapy has become a prevalent and reliable approach for the safe and efficient treatment of cancer. In this work, an acid-sensitive nanoprodrug (O@PD) targeting CD44 receptors was produced using Schiff-base linkages or electrostatic interactions from oxidized hyaluronic acid (OHA), PQ, and doxorubicin (DOX). The CD44-targeting prodrug system in triple-negative breast cancer (TNBC) cells was designed to selectively release DOX and PQ into the acidic tumor microenvironment and cellular endosomes. DOX was employed to investigate the cellular uptake and ex-vivo drug distribution of O@PD nanoprodrugs. PQ-induced autophagy suppression combined with DOX has a synergistic fatal impact in TNBC. O@PD nanoprodrugs demonstrated robust anticancer efficacy as well as excellent biological safety, making them suitable for clinical use.
研究领域:
癌症研究
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2020
·
IF 4.152
Beibei Lu,Fan Xiao,Zhenyuan Wang,Binshen Wang,Zuchen Pan,Weiwei Zhao,Zhenye Zhu,Jiaheng Zhang
Currently, available nanoscale anticancer drug delivery systems have low targeting and release efficiency, limiting their therapeutic effects. Thus, tumor-targeting nanocarriers for self-assembly of amphiphilic polymer–drug conjugates are urgently needed to improve drug targeting and treatment efficacy. Here, we report the construction of a stable, reduction-sensitive prodrug conjugate based on hyaluronic acid-grafted pH-sensitive doxorubicin (DOX). The amphiphilic prodrug copolymer self-assembled into spherical nanoparticles in aqueous solution and exhibited an average diameter of 150 nm. Prodrug micelles were stable in a normal physiological environment and achieve selective and rapid release under acidic pH and/or high reduction conditions. Cell Counting Kit-8, flow cytometry, and live cell imaging assays showed that the prodrug had high targeting and antitumor activity against CD44 receptors. Moreover, in vivo pharmacokinetics and biodistribution studies showed that the prodrug had a longer circulation time in BALB/c mice and higher accumulation in 4T1 tumors. Interestingly, the prodrug could effectively treat tumors with few side effects. These results showed that the DOX prodrug micelles developed in this study may have great potential in targeted therapy.
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
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 32
·7233-7252
·
IF 5.344
Hui Zhang,Xin-Yuan Sun,Xue-Wu Chen,Jian-Ming Ouyang
We studied the protection of degraded Porphyra yezoensis polysaccharide (PYP) on human proximal tubular epithelial cells (HK-2) from cytotoxicity of nano-calcium oxalate monohydrate (COM) crystal, and the regulation of adhesion and endocytosis of the COM crystal. Four degraded fractions, namely, PYP1, PYP2, PYP3, and PYP4, were successfully obtained, with molecular weights (Mws) of 576.2, 49.5, 12.6, and 4.02 kDa, respectively. PYP protection reduced the crystal toxicity, prevented the destruction of cell morphology and cytoskeleton, inhibited the production of reactive oxygen species and the decline of lysosomal integrity, and reduced the expression of osteopontin and transmembrane protein (CD44). PYPi inhibited the adhesion and endocytosis of HK-2 cells by nano-COM. Endocytic COM crystals were accumulated in the lysosomes. With decreasing molecular weight, the ability of PYP to reduce cell damage and inhibit cell adhesion and endocytosis increased. PYP4, which has the smallest molecular weight, weaker intramolecular hydrogen bonds and more reducing groups, showed the best biological activity. PYPi can reduce the oxidative damage of the crystal to the cell, inhibit the adhesion and endocytosis of the crystal, and reduce the risk of kidney stone formation. Therefore, PYP, especially PYP4, has potential for use as a green drug to inhibit the formation and recurrence of calcium oxalate stones.
研究领域:
药理学
·
肾病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Yuhui Wang,Shilong Ma,Xuanyu Liu,Yan Wei,Haofeng Xu,Ziwei Liang,Yinchun Hu,Xiaojie Lian,Di Huang
Hepatocellular carcinoma (HCC) is one of the deadliest tumors in the world with a high rate of recurrence and metastasis. Therefore, the most pressing issue today is the development of new drugs, diagnostic and therapeutic approaches for effective cancer treatment. Cancer stem cells (CSCs) play a pivotal role in tumor recurrence, tumor resistance, and tumor metastasis, which provides a new perspective on the development of liver cancer. In the study, a high-temperature thermal breakdown approach was used to create composite magnetic nanocubes modified by polyethyleneimine (PEI) and hyaluronic acid (HA). The Fe 3 O 4 nanocubes can recognize HCC stem cells via receptor−ligand binding of HA and CD44 (HA receptor). While loading a small molecule LDN193189 inhibited the expression of stemness-related genes OCT4 and Nanog . More crucially, the Fe 3 O 4 nanocubes significantly suppressed HCC cell proliferation and migration by regulating the expression of epithelial-mesenchymal transition (EMT) process markers E-cadherin, Vimentin , and N-cadherin. Dual targeting using magnetic and receptor-mediated targeting improved the uptake of the drug delivery system. Our findings imply that the medication delivery method might be a potential therapeutic strategy for HCC.
研究领域:
癌症生物学
·
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
Acta Biomaterialia
·
2016
·
IF 6.008
Zhoujiang Chen,Nan He,Maohua Chen,Long Zhao,Xiaohong Li
Micelles self-assembled from drug-conjugated polymers indicate advantages in alleviating the premature release before reaching the intended site. Hyaluronic acid (HA) is known to specifically bind with a transmembrane glycoprotein CD44 , overexpressed in many types of cancerous cells, and can also be served as micelle carriers. However, an excess amount of drug conjugation to HA backbone may be detrimental to the receptor-mediated cellular uptake. Up to now, the effect of conjugation densities of drugs has never been determined on the physical properties and biological performance of resulting micelles. In the current study, camptothecin (CPT) was conjugated on HA through 3,3′-dithiodipropionic acid to self-assemble into reduction-sensitive micelles. The substitution degrees of CPT on HA backbone were tuned from around 4–20%, to clarify the effects on the cellular uptake efficiency and cytotoxicities of micelles, as well as the tumor accumulation and antitumor efficacy. The CPT substitution degree of around 15% on HA resulted in micelles with a higher cytotoxicity to 4T1 cells and achieved a better balance between the cellular uptake and reduction-triggered drug release, compared with other micelles. In contrast to a fast kidney clearance and an even distribution in major organs after intravenous injection of free CPT, the optimized micelles were accumulated in tumors, livers and lungs. The micelle content indicated a significant decrease in livers after 24 h, while that in tumors displayed a significant increase to 4.9% of the injection dose. The tumor accumulation of micelles led to strong tumor suppression with minimal systemic toxicity. The in situ tumor inhibition and the accumulation of micelles in liver and lungs inhibited tumor metastasis to these tissues. It demonstrates a feasible strategy to develop drug-HA conjugate micelles with a concise and tunable structure for tumor targeting and reduction-triggered release. Statement of Significance Hyaluronic acid (HA) can be served as micelle carriers and targeting ligands to tumor cells. However, the effects of drug conjugation densities on the physical profile and biological performance of resulting micelles have never been investigated. In the current study, camptothecin is conjugated on HA with reduction-sensitive linkers, and the substitution degrees of camptothecin on HA backbone vary from around 4–20%. The micelles with a substitution degree of around 15% achieve a better balance between the cellular uptake and reduction-triggered drug release and a higher cytotoxicity than others. It demonstrates a feasible strategy to develop drug-HA conjugate micelles with a concise and tunable structure for tumor targeting and reduction-triggered release.
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
危险品化学品经营许可证（带存储）