DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2017
·
IF 2.295
Haohuan Li,Yi Chen,Yueyang Deng,Yue Wang,Xue Ke,Tianyuan Ci
Cationic liposome is a potential nanocarrier to deliver drugs to solid tumor with proven efficiency in targeting tumor tissues. However, the major limitation is their charge-related instability and blood toxicity via intravenous injection. In order to overcome these problems and to maintain tumor targeting potency, we modified the cationic liposomes with low molecular weight heparin (LMWH) to obtain series of liposomes with different surface charges. Both in vitro and in vivo studies including serum stability, blood hemolysis, cellular uptake, cytotoxicity and in vivo biodistribution were evaluated. The results indicated the cationic liposome with surface charge of 5 mV (denoted as LLip-C) had the similar stability in serum and mild hemocytolysis compared with that of anionic liposome (LLip-D), but better cellular uptake owing to electrostatic interaction between cationic liposomes and cell membranes. Furthermore, we prepared curcumin-loaded liposomes to investigate the therapy efficiency. The intracellular distribution of curcumin-loaded LLip-C (Curcumin-LLip-C) was inclined to locate in cytoplasm and nuclei than curcumin-loaded LLip-D (Curcumin-LLip-D). In vitro cytotoxicity of Curcumin-LLip-C also exhibited higher inhibition of tumor cells than that of Curcumin-LLip-D. These results certified that a slightly positive surface charge of nanocarriers could achieve the balance between well antitumor efficiency and mild adverse effects.
研究领域:
药剂学
·
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
ADVANCED MATERIALS
·
2025
·
IF 26.8
Yaqing Kang,Xiaoqing Han,Shijie Zhou,Xingbo Wang,Yanjing Wang,Panpan Song,Xiaochen Su,Mengmeng Qin,Dongyang Qian,Huan Meng,Jiao Yan,Fang Pu,Haiyuan Zhang
Rheumatoid arthritis microenvironment (RAM) contains complex pathogenic mediators that interact dynamically to drive the progression of rheumatoid arthritis (RA). However, most current RA treatments are single-target interventions, exerting limited impact on RAM. Herein, apoptotic extracellular vesicles (ApoEV) are constructed for programmable regulation of the neutrophil-macrophage-ROS pathogenic axis, aiming to reconstruct RAM and improve RA therapy. Mesenchymal stem cells (MSCs) are pretreated with dexamethasone (Dex) and induced apoptosis to produce Dex-loaded and FasL-overexpressing ApoEV (D@ApoEV FasL ), which is further modified with low-molecular-weight heparin (LMWH) through a ROS-responsive cleavage linker to form D@ApoEV FasL ∩L. After intravenous injection into RA mice, D@ApoEV FasL ∩L targeted the inflamed joints based on their MSC-derived feature and blocked neutrophil recruitment through binding to P-selectin on vascular endothelial cells. In response to high ROS, D@ApoEV FasL ∩L shed LMWH and exposed FasL, inducing neutrophil apoptosis through the Fas/FasL signaling pathway. Subsequently, the apoptotic neutrophils triggered macrophage reprogramming from M1 to M2 phenotype, and the released Dex significantly reduced the oxidative damage. Various in vitro and in vivo assessments have confirmed that D@ApoEV FasL ∩L can effectively regulate neutrophils, macrophages, and ROS, trigger an immune cascade, and restore intra-articular immune homeostasis, exhibiting an effective RAM reconstruction ability and a promising therapeutic effect for RA.
研究领域:
免疫学
·
风湿病学
·
纳米医学
·
细胞治疗
·
转化医学
·
炎症生物学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2024
·Vol. 47
·期 17
·2400367
·
IF 2.8
Yang Zhao,Jie Li,Yang Yang,Yujie Bi,Changyu Cai,Yanxiong Ke
In this study, spherical silica with pore size varied from 30 to 200 Å was synthesized by pseudomorphic transformation at atmospheric pressure. 40–80 Å silica particles with a narrow pore distribution were obtained by using quaternary amine cationic surfactants and different kinds of swelling agents, including polypropylene glycol, 1,3,5-trimethylbenzene, alkanes, and alkanols. Alkyl imidazolium ionic liquid surfactants were used to synthesize large pore size distribution silica spheres with pore sizes in the range of 110–200 Å. All these silica particles can be synthesized under mild conditions within 12 h, which provides a facile synthesis method for the preparation of a chromatographic matrix with tunable pore size. The method is reproducible and the relative standard deviation of silica sphere pore structure parameters in scaled-up preparations is less than 6%. The pore size on the fraction of low-molecular-weight heparin (LMWH) was investigated in size exclusion chromatography. Matrixes with different pore size distributions have various size exclusion regions. By using UPS-60-Diol columns in a twin-column recirculation separation process, LMWH with >85% heparin with molecular weight within the range of 3000–8000 Da were separated in five-column volumes.
研究领域:
材料科学
·
化学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
Xiaoye Yang,Xiaoqun Shi,Jianbo Ji,Guangxi Zhai
The development of imaging-guided smart drug delivery systems for combinational photodynamic/chemotherapy of the tumor has become highly demanded in oncology. Herein, redox-responsive theranostic polymeric nanoparticles (NPs) were fabricated innovatively using low molecular weight heparin (LWMH) as the backbone. Chlorin e6 (Ce6) and alpha-tocopherol succinate (TOS) were conjugated to LMWH via cystamine as the redox-sensitive linker, forming amphiphilic Ce6-LMWH-TOS (CHT) polymer, which could self-assemble into NPs in water and encapsulate paclitaxel (PTX) inside the inner core (PTX/CHT NPs). The enhanced near-infrared (NIR) fluorescence intensity and reactive oxygen species (ROS) generation of Ce6 were observed in a reductive environment, suggesting the cystamine-switched “ON/OFF” of Ce6. Also, the in vitro release of PTX exhibited a redox-triggered profile. MCF-7 cells showed a dramatically higher uptake of Ce6 delivered by CHT NPs compared with free Ce6. The improved therapeutic effect of PTX/CHT NPs compared with mono-photodynamic or mono-chemotherapy was observed in vitro via MTT and apoptosis assays. Also, the PTX/CHT NPs exhibited a significantly better in anti-tumor efficiency upon NIR irradiation according to the results of in vivo combination therapy conducted on 4T1-tumor-bearing mice. The in vivo NIR fluorescence capacity of CHT NPs was also evaluated in tumor-bearing nude mice, implying that the CHT NPs could enhance the accumulation and retention of Ce6 in tumor foci compared with free Ce6. Interestingly, the anti-metastasis activity of CHT NPs was observed against MCF-7 cells by a wound healing assay, which was comparable to LMWH, suggesting LMWH was promising for construction of nanocarriers for cancer management.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2016
·
IF 4.843
Jiang Ni,Fengchun Tian,Fatima Zohra Dahmani,Hui Yang,Deren Yue,Shuwang He,Jianping Zhou,Jing Yao
The low oral bioavailability of numerous drugs has been mostly attributed to the significant effect of P-gp-mediated efflux on intestinal drug transport. Herein, we developed mixed polymeric micelles (MPMs) comprised of curcumin-carboxymethyl chitosan (CNC) conjugate, as a potential inhibitor of P-gp-mediated efflux and gastrointestinal absorption enhancer, and low-molecular-weight heparin-all-trans-retinoid acid (LHR) conjugate, as loading material, with the aim to improve the oral absorption of P-gp substrate drugs. CNC conjugate was synthesized by chemical bonding of curcumin (Cur) and carboxymethyl chitosan (CMCS) taking advantage of the inhibition of intestinal P-gp-mediated secretion by Cur and the intestinal absorption enhancement by CMCS. The chemical structure of CNC conjugate was characterized by 1H NMR with a degree of substitution of Cur of 4.52–10.20%. More importantly, CNC conjugate markedly improved the stability of Cur in physiological pH. Cyclosporine A-loaded CNC/LHR MPMs (CsA-CNC/LHR MPMs) were prepared by dialysis method, with high drug loading 25.45% and nanoscaled particle size (∼200 nm). In situ single-pass perfusion studies in rats showed that both CsA + CNC mixture and CsA-CNC/LHR MPMs achieved significantly higher Ka and Peff than CsA suspension in the duodenum and jejunum segments (p < 0.01), which was comparable to verapamil coperfusion effect. Similarly, CsA + CNC mixture and CsA-CNC/LHR MPMs significantly increased the oral bioavailability of CsA as compared to CsA suspension. These results suggest that CNC conjugate might be considered as a promising gastrointestinal absorption enhancer, while CNC/LHR MPMs had the potential to improve the oral absorption of P-gp substrate drugs.
研究领域:
药学
·
药物递送系统
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 8
·2172-2188
·
IF 5.831
Haifeng Sun,Dinglingge Cao,Yanhong Liu,Hui Wang,Xue Ke,Tianyuan Ci
Tumor metastasis has become a major obstacle for the clinical treatment of malignant breast cancer. Thus, a delivery system capable of both antitumor and anti-metastasis efficacy is desired. In this work, a low molecular weight heparin (LMWH)-based reduction-sensitive delivery system was developed, aiming to combine the properties of both the antitumor drug and active excipients to achieve a synergistic antitumor and anti-metastatic efficiency as well as resolving the potential adverse effects of both doxorubicin and LMWH. That is, the efficiency of DOX could be enhanced and its toxicity could be lowered. Meanwhile, the biological properties of LMWH could be strengthened and its bleeding risk could also be alleviated. Briefly, drug-loaded crosslinked nanoparticles (DOX/cLLHC2) had a longer blood circulation time and exhibited a rapid reduction-triggered release of DOX. The in vitro assays revealed that DOX/cLLHC2 exhibited a higher cellular uptake and cytotoxicity compared to free DOX. Meanwhile, for the existence of LMWH, DOX/cLLHC2 inhibited cell migration and invasion, as well as effectively inhibited the tube-like formation of human umbilical vein endothelial cells. DOX/cLLHC2 possessed a superior tumor accumulation compared to lipoic acid unmodified nanoparticles and free DOX. Also, DOX/cLLHC2 exhibited encouraging antitumor and anti-metastasis efficiency in an orthotopic breast cancer model. Overall, DOX/cLLHC2 could exert antitumor, anti-metastasis, and anti-angiogenesis efficacy simultaneously as well as having lower systemic toxicity, which makes it suitable for the therapy of metastatic breast carcinoma.
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
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Peiyi She,Hong Xu,Yating Shan,Gaocan Li,Yunbing Wang
As a major causative agent of cardiovascular disease, atherosclerosis (AS) is typically characterized by aberrant lipid buildup and persistent vascular inflammation. However, early AS is difficult to recognize by traditional imaging methods owing to the absence of evident symptoms. Therefore, a reactive oxygen species (ROS)-responsive theranostic nanoplatform (PA/HFLCD) is developed in order to modulate the endothelial cell-macrophage crosstalk in a pathological environment and to enable precise detection of early plaques. π-conjugated polymers (PFDPP-Se) are synthesized by palladium-catalyzed arylation polymerization reaction. β-Cyclodextrin-modified oxidized dextran is self-assembled with ferrocene and linoleic acid co-modified low molecular weight heparin, incorporating PFDPP-Se as photoacoustic contrast agents. Excessive ROS at the plaque facilitates the breakdown of ferrocene binding to β-cyclodextrins, releasing both PFDPP-Se and therapeutic agents to identify lesions by photoacoustic imaging and balancing endothelial cell-macrophage crosstalk. In vivo studies confirm that PA/HFLCD enables precisely targeted photoacoustic diagnostics and regulates the inflammatory microenvironment consisting of endothelial cells and macrophages in ApoE −/− mice, leading to plaque regression. This synergistic amalgamation of diagnostic and therapeutic attributes renders PA/HFLCD not only a formidable instrument in combating AS, but also a reference for the theranostics of various inflammatory diseases.
研究领域:
纳米医学
·
心血管疾病
·
分子影像学
·
诊疗一体化
·
炎症生物学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2016
·Vol. 5
·期 12
·1447-1461
·
IF 5.76
Fatima Zohra Dahmani,Yan Xiao,Juan Zhang,Yao Yu,Jianping Zhou,Jing Yao
Combination of antiangiogenesis and chemotherapy holds vast promise for effective inhibition of tumor proliferation and invasion. Herein, a multifunctional self-assembled nanosystem consisting of amphiphilic c(RGDyK)-functionalized low-molecular-weight heparin–gambogic acid conjugate (cRHG) is developed, using c(RGDyK) peptide as α v β 3 integrin targeting moiety to realize a double-targeted delivery to both tumor cells and angiogenic vasculature. cRHG with a markedly decreased anticoagulant activity can self-assemble into nanosized particles (around 150 nm). cRHG nanoparticles effectively inhibit vascular endothelial growth factor (VEGF)-triggered tube-like formation of HUVEC and neovascularization of subcutaneous Matrigel plugs. More importantly, the targeting ability of cRHG nanoparticles is revealed by their efficient internalization by α v β 3 integrin-positive cells (U87MG and HUVEC) in vitro and obvious accumulation of Cy7/cRHG in the tumor site with strong fluorescence signals in both cancer cells and neovasculature. Besides, cRHG maintains the in vitro cytotoxic activity of gambogic acid, while achieving the highest in vivo antitumor activity in U87MG mouse xenograft model and displaying better safety profile than free drugs solutions. Mechanistic investigations reveal the substantial inhibition of hypoxia-inducible factor-1 alpha, VEGF, and CD31 expression by cRHG nanoparticles with remarkable down-regulation of VEGFR2 phosphorylation. These results suggest that cRHG nanoparticles provide a versatile nanoplatform for efficacious combinatorial tumor therapy.
研究领域:
纳米医学
·
癌症治疗
·
药学科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2018
·
IF 6.383
Fengchun Tian,Fatima Zohra Dahmani,Jianan Qiao,Jiang Ni,Hui Xiong,Tengfei Liu,Jianping Zhou,Jing Yao
Several obstacles are currently impeding the successful treatment of breast cancer, namely impaired drug accumulation into the tumor site, toxicity to normal cells and narrow therapeutic index of chemotherapy, multidrug resistance (MDR) and the metastatic spread of cancer cells through the blood and lymphatic vessels. In this regard, we designed a novel multifunctional nano-sized drug delivery system based on LyP-1 peptide-modified low-molecular-weight heparin-quercetin conjugate (PLQ). This nanosystem was developed for targeted co-delivery of multiple anticancer drugs to p32-overexpressing tumor cells and peritumoral lymphatic vessels, using LyP-1 peptide as active targeting ligand, with the aim to achieve a targeted combinatorial chemo/angiostatic therapy and MDR reversal. The cellular uptake of PLQ nanoparticles by p32-overexpressing breast cancer cells was significantly higher than nonfunctionalized nanoparticles. Besides, the anti-angiogenic activity of PLQ nanoparticles was proven by the effective inhibition of the bFGF-induced neovascularization in subcutaneous Matrigel plugs. More importantly, PLQ/GA nanoparticles with better targeting ability toward p32-positive tumors, displayed a high antitumor outcome by inhibition of tumor cells proliferation and angiogenesis . Immunohistochemistry and western blot assay showed that PLQ/GA nanoparticles significantly disrupted the lymphatic formation of tumor, and inhibited the P-glycoprotein (P-gp) expression in MCF-7 tumor cells, respectively. In conclusion, PLQ/GA nanoparticles provide a synergistic strategy for effective targeted co-delivery of chemotherapeutic and antiangiogenic agents and reversing MDR and metastasis in breast cancer. Statement of Significance Herein, we successfully developed a novel amphiphilic nanomaterial , LyP-1-LMWH-Qu (PLQ) conjugate, consisting of a tumor-targeting moiety LyP-1, a hydrophobic quercetin (a multidrug resistance [MDR]–reversing drug) inner core, and a hydrophilic low-molecular-weight heparin (an antiangiogenic agent) outer shell for encapsulating and delivering a hydrophobic chemotherapeutic agent (gambogic acid). This versatile nanoplatform with multiple targeted features, i.e., dual chemo/angiostatic effects, destruction ability of the peritumoral lymphatic vessels, and reversal of MDR, resulted in a significantly stronger antitumor efficacy and lower toxic side effect than those of nontargeted nanoparticles and the free drug solution. Therefore, this versatile nanosystem might provide a novel insight for the treatment and palliation of breast cancer by targeted co-delivery of chemo/antiangiogenic agents and reversing MDR and metastasis.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
癌症治疗
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Manxiang Wu,Dong Xie,Lianfu Wang,Zhusheng Liu,Hongying Bao,Tao Ye,Chengyuan Hong,Jie Lin,Tianxiang Chen,Aiguo Wu,Qiang Li
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Its pathogenesis involves aberrant activation and aggressive proliferation of fibroblast-like synoviocytes (FLS), excessive macrophage infiltration, and disrupted M1/M2 macrophage polarization within the synovial microenvironment (SME). However, current therapies remain inadequate for precise SME modulation, often leading to limited efficacy and poor prognosis. To address this challenge, we developed a multifunctional nanocapsule, termed RP/HP@Mn/L, which is composed of a low molecular weight heparin (LMWH)-modified, Mn 2+ -doped hollow mesoporous polydopamine (HP) nanocarrier co-loaded with rapamycin (Rap) and paeoniflorin (Pae). This nanocapsule's dual-ligand strategy targets P-selectin on inflamed endothelial cells and integrin αM on inflammatory macrophages, enabling precise spatiotemporal accumulation at the pathological site. This nanocapsule enables spatiotemporally specific targeting of both inflammatory endothelial cells and inflammatory macrophages, thereby enhancing precise drug delivery to pathological sites. Mechanistic investigations revealed that RP/HP@Mn/L, in combination with mild photothermal therapy (PTT) mediated by HP, effectively suppressed FLS proliferation and invasion. Concurrently, it promoted the polarization of macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. These synergistic effects facilitated the remodeling of the SME, thereby alleviating synovitis and enhancing bone repair in RA. In conclusion, this study proposes a spatiotemporally targeted combinatorial nanotherapeutic strategy that integrates multimodal mechanisms for SME modulation. This approach represents a promising therapeutic platform for improving outcomes in RA and other autoimmune disorders.
研究领域:
纳米医学
·
免疫治疗
·
风湿病学
·
生物医学工程
·
药物递送系统
·
炎症性疾病
·
自身免疫性疾病
✓ 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）