NANOTECHNOLOGY
·
2022
·Vol. 33
·期 27
·275604
·
IF 3.953
Kai Cheng,Jie Zhou,Yujie Zhao,Yu Chen,Lan Ming,Da Huang,Rui Yang,Zhenyu Lin,Daozhen Chen
Herein, an amphiphilic block copolymer CD44-targeting peptide-conjugated polyethylene glycol-block-hydroxyethyl starch-block-poly (L-lactic acid) (CD44p-conjugated PEG-b-HES-b-PLA) are synthesized, which could self-assemble into the pH-responsive and CD44-targeting polymer micelles against breast cancer cells MDA-MB-231. Emodin (Emo) is a natural anthraquino with pharmacological activities in anti-tumor effects. However, Emo suffers from poor water solubility, low biocompatibility, rapid systemic elimination, and off-target side effects, resulting in unsatisfactory treatment outcomes. Nanotechnology-based drug delivery systems have proven great potential for cancer chemotherapy. The constructed polymeric micelles Emo@CD44p-PM have exhibited an average size of 154.5 ± 0.9 nm characterized by DLS and TEM. Further, the Emo@CD44p-PM have effective Emo-loading capacity, good thermal stability, and pH responsiveness. Intracellular uptake study shows the enhanced cellular internalization of Emo@CD44p-PM due to the increased exposure of CD44p enhances the cellular internalization of Emo@CD44p-PM effectively. Furthermore, the in vitro results showed Emo@CD44p-PM has been observed good biocompatibility and anti-tumor effects. Therefore, the polymeric micelles Emo@CD44p-PM provide a promising delivery strategy of targeted therapy for breast cancer.
研究领域:
纳米技术
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药学
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癌症研究
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高分子化学
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产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Fugen Wu,Xingsi An,Shize Li,Chenyu Qiu,Yixuan Zhu,Zhanzheng Ye,Shengnan Song,Yunzhi Wang,Dingchao Shen,Xinyu Di,Yinsha Yao,Wanling Zhu,Xinyu Jiang,Xianbao Shi,Ruijie Chen,Longfa Kou
Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death (ICD), making it a promising strategy for clinical application. Alantolactone (A) was found to augment the anticancer efficacy of paclitaxel (P) at a molar ratio of 1:0.5 (P:A) through induction of more potent ICD via modulation of STAT3 signaling pathways. Nano drug delivery systems can synergistically combine natural drugs with conventional chemotherapeutic agents, thereby enhancing multi-drug chemoimmunotherapy. To improve tumor targeting ability and bioavailability of hydrophobic drugs, an amphiphilic prodrug conjugate (HA-PTX) was chemically modified with paclitaxel (PTX) and hyaluronic acid (HA) as a backbone. Based on this concept, CD44-targeted nanodrugs (A@HAP NPs) were developed for co-delivery of A and P in colorectal cancer treatment, aiming to achieve synergistic toxicity-based chemo-immunotherapy. The uniform size and high drug loading capacity of A@HAP NPs facilitated their accumulation within tumors through enhanced permeability and retention effect as well as HA-mediated targeting, providing a solid foundation for subsequent synergistic therapy and immunoregulation. In vitro and in vivo studies demonstrated that A@HAP NPs exhibited potent cytotoxicity against tumor cells while also remodeling the immune-suppressive tumor microenvironment by promoting antigen presentation and inducing dendritic cell maturation, thus offering a novel approach for colorectal cancer chemoimmunotherapy.
研究领域:
肿瘤学
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药学
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纳米技术
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Qing-zhu Zhang,Hui-yuan Xu,Chao-yan Feng,Chu-hao Zhang,Kun Ren,Ying-ni Pan,Dong-mei Wang,Shu-meng Ren,Xiao-qiu Liu
Ethnopharmacological relevance The leaves of Quercus dentata Thunb. (QD), a member of the Fagaceae family and genus Quercus , with distributions in China, Japan, Korea, and other regions. As recorded in the Ben Cao Gang Mu (Compendium of Materia Medica) and other classical Chinese medical texts, QD has been traditionally employed in Traditional Chinese Medicine (TCM) for their hemostatic and diuretic effects and has been used to treat urinary stones ( Lin Zheng ). It is also the main ingredient of the Mishitong capsule (MST), a Chinese patent drug, used for kidney stones and ureteral stones. Nonetheless, the specific active ingredients and the mechanisms of QD in treating kidney stones remain to be elucidated, which is crucial for advancing the scientific understanding and clinical application of this traditional medicine. Aim of study This study aimed to identify the active constituents of QD water extract (QDWE), explore its inhibitory effects on kidney stones through in vitro and in vivo studies, and elucidate the underlying mechanisms of the OPN/CD44 axis and the NLRP3 signaling pathway to provide a full understanding of its potential as a novel treatment approach against kidney stones. Materials and methods The micromolecular components in the supernatant of QDWE (QDS) were analyzed by UPLC-Q-Exactive-Orbitrap-MS and the monosaccharide composition of the macromolecular polysaccharide components in the crude polysaccharide (QDP) was determined by pre-column derivatization in HPLC. The effects of QDWE, QDS and QDP on the shape, size, and structure of calcium oxalate (CaOx) crystals in vitro were explored by XRD, FTIR and SEM. The effects of QDWE, QDS and QDP on CaOx kidney stones in SD rats induced by ethylene glycol and VD 3 were compared in vivo . Furthermore, the underlying mechanisms of OPN/CD44 and NLRP3 pathways were investigated by Western blot analysis. Results There were 32 compounds identified in QDS. The monosaccharide composition ratio of QDP was Man: L-Rha: D-GlcA: D-GalA: D-Glc: D-Gal: L - Ara = 1.01: 22.52: 8.27: 38.61: 3.43: 17.80: 6.38, indicating a mixture of pectin-type acidic heteropolysaccharides. QDP had a more significant inhibitory effect on CaOx crystals in vitro than QDWE, which can inhibit the formation of CaOx monohydrate crystals (COM) and convert them into thermodynamically unstable CaOx dihydrate (COD) crystals. The high dose of QDWE exhibited significant in vivo efficacy ( P < 0.05), including anti-calculus, diuretic effects, and kidney protection, marked by decreased calcification and stone formation, alongside improved kidney vitality. Furthermore, the protective effects of QDWE were demonstrated to be associated with the OPN/CD44 and NLRP3 pathways. Conclusion The studies identified and analyzed the active constituents of QDWE. Among these, QDP significantly inhibited CaOx crystal generation in vitro and could be a potential component for the treatment of urinary stones in QDWE. Moreover, the results indicated that QDWE had a remarkable therapeutic effect on CaOx stones by modulating the OPN/CD44 axis to affect stone formation and the NLRP3 signaling pathway to mediate inflammation, providing an experimental basis for the mechanism of anti-urinary stone and deep development of QD.
研究领域:
药理学
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民族药理学
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泌尿学
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传统中药
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Qiang Chen,Chunjing Guo,Xiudi Zhou,Yanguo Su,Huimin Guo,Min Cao,Jing Li,Yue Zhang,Weiyi Zhao,Xin Gao,Shuqi Mi,Daquan Chen
Currently, very limited therapeutic approaches are available for the drug treatment of atherosclerosis(AS). H 2 S-donor is becoming a common trend in much life-threatening research. Several studies have documented that H 2 S-lyase is predominantly present in endothelial cells. N-Acetylneuraminic acid (SA), natural carbohydrate, binds specifically to the E -selectin receptor of endothelial cells. Meanwhile, recent studies related to Chondroitin sulfate have excellent target binding ability with CD44 receptor. We conjecture that the N-Acetylneuraminic acid and Chondroitin sulfate modified nanomicelles not only enhances the accumulation of the drug but also cleaves the H 2 S donor in the lesion, thus one stone two birds. Given these findings, we synthesized two kinds of nanoparticles, Carrier I (SCCF) and Carrier II (SCTM), for atherosclerosis to validate our guesses. Initially, S-allyl-L-cysteine and 4-methoxyphenylthiourea were used as H 2 S donors for SCCF and SCTM, respectively. After the introduction of ROS-sensitive groups. Then, micelles with N-Acetylneuraminic acid and Chondroitin sulfate were prepared to load rapamycin(RAP). Further, in atherosclerosis Oil Red O staining (ORO) results confirmed remarkable treatment effect with [email protected] and [email protected] Thus, we conclude that the effect of dual-targeting nanomicelles with ROS-sensitive H 2 S donor based on N-Acetylneuraminic acid and Chondroitin sulfate will have a better role in atherosclerosis.
研究领域:
药学
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纳米技术
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心血管疾病
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Liting Zhu,Linjie Mu,Xiaoqiu Ni,Feng Wang,Xinyi Peng,Yujiu Gao,Tingting Wei,Congcong Zeng,Yongheng Bai,Fangyan Wang,Zhengzhong Yuan,Jinguo Cheng
Ethnopharmacological relevance Xin-Zi-Sheng-Wan Decoction (XZSWD), a formulation rooted in the classic Zi-Sheng Pill first recorded in the Qing-dynasty compendium “ Golden Mirror of Medicine ,” is traditionally employed to resolve turbid pathogenic stagnation and restore metabolic equilibrium. Modern ethnopharmacological studies reveal a marked uric acid–lowering effect, although its precise molecular mechanisms have yet to be fully clarified. Aim of the study This study aimed to evaluate the therapeutic efficacy of XZSWD in hyperuricemia (HUA)-induced kidney injury and to elucidate its molecular mechanisms. Methods UPLC-QTOF/MS was used to identify compounds in XZSWD medicated serum. A HUA mouse model was induced by potassium oxonate and hypoxanthine to evaluate the therapeutic effects of XZSWD on renal injury. RNA-Seq, qRT-PCR, Western blot, immunofluorescence, and flow cytometry were applied to investigate immune infiltration and key signaling pathways. A THP-1/HK-2 co-culture system combined with SPP1 overexpression and knockdown was used to explore the molecular mechanisms. Results 99 compounds were identified in XZSWDS. XZSWD improved renal function, reduced serum uric acid levels, and downregulated macrophage-related inflammatory genes while modulating mixed M1/M2 polarization. XZSWD also inhibited the SPP1-CD44 axis and downstream SRC/FAK/β-Catenin signaling to reduce renal extracellular matrix (ECM) deposition. In vitro, SPP1 was identified as a critical target mediating these effects. Conclusions XZSWD alleviates HUA-induced renal injury by suppressing macrophage-mediated inflammation via regulation of the SPP1–CD44 axis and SRC/FAK/β-Catenin signaling, highlighting its therapeutic potential for HUA-related renal dysfunction.
研究领域:
民族药理学
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肾脏病学
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免疫学
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信号转导
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植物化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Duo Li,Xiaoli Wang,Kaishuo Han,Yaqian Sun,Ting Ren,Guohui Sun,Na Zhang,Lijiao Zhao,Rugang Zhong
Carmustine (BCNU) is a typical chemotherapy used for treatment of cerebroma and other solid tumors, which exerts antitumor effect by inducing DNA damage at O 6 position of guanine. However, the clinical application of BCNU was extremely limited due to the drug resistance mainly mediated by O 6 -alkylguanine-DNA alkyltransferase (AGT) and absence of tumor-targeting ability. To overcome these limitations, we developed a hypoxia-responsive nanomicelle with AGT inhibitory activity, which was successfully loaded with BCNU. In this nano-system, hyaluronic acid (HA) acts as an active tumor-targeting ligand to bind the overexpressing CD44 receptors on the surface of tumor cells. An azo bond selectively breaks in hypoxic tumor microenvironment to release O 6 -benzylguanine (BG) as AGT inhibitor and BCNU as DNA alkylating agent. The obtained HA-AZO-BG NPs with shell core structure had an average particle size of 176.98 ± 11.19 nm and exhibited good stability. Meanwhile, HA-AZO-BG NPs possessed a hypoxia-responsive drug release profile. After immobilizing BCNU into HA-AZO-BG NPs, the obtained HA-AZO-BG/BCNU NPs exhibited obvious hypoxia-selectivity and superior cytotoxicity in T98G, A549, MCF-7 and SMMC-7721 cells with IC 50 at 189.0, 183.2, 90.1 and 100.1 μm, respectively, under hypoxic condition. Near-infrared imaging in HeLa tumor xenograft models showed that HA-AZO-BG/DiR NPs could effectively accumulate in tumor site at 4 h of post-injection, suggesting its good tumor-targetability. In addition, in vivo anti-tumor efficacy and toxicity evaluation indicated that HA-AZO-BG/BCNU NPs was more effective and less harmful compared to the other groups. After treatment, the tumor weight of HA-AZO-BG/BCNU NPs group was 58.46 % and 63.33 % of the control group and BCNU group, respectively. Overall, HA-AZO-BG/BCNU NPs was expected to be a promising candidate for targeted delivery of BCNU and elimination of chemoresistance.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Yinzhuo Xie,Wei Xu,Zheng Jin,Kai Zhao
Curcumin (CUR) has a regulatory effect on the gut microbiota (GM), and its significant anti-inflammatory properties make it a research hotspot for inflammatory bowel disease (IBD) treatment. However, the low bioavailability and poor pharmacokinetic properties of CUR limit its practical application. Herein, CD44 and GM dual-targeted nanoparticles (NPs) loaded with CUR ( [email protected] NPs) were derived from a quaternized chitosan and surface functionalization with chondroitin sulfate (Chs). The generated [email protected] NPs had an ideal average particle size (238.9 nm), a uniform size distribution, and a positive surface charge (+41.93 mV). Strikingly, the [email protected] NPs had a good sustained-release effect in a simulated gastrointestinal environment and exhibited the full drug release when in a simulated colon environment. Moreover, Chs functionalization endowed the NPs with a notable CD44-targeted drug delivery ability and thereby enhanced the CUR content in the plasma of SD rats. The biodistribution of the [email protected] NPs in vivo indicated that the NPs could prolong the intestinal residence time, thereby promoting the interaction between CUR and GM. Most importantly, in a DSS-induced colitis mouse model, the [email protected] NPs decreased the disease activity index, improved the oxidative stress and inflammation condition, promoted the production of short-chain fatty acids (SCFAs), regulated immune cells, and maintained intestinal microbiome homeostasis. This study demonstrates that [email protected] NPs, which exhibit excellent biocompatibility and biodegradability, on-demand drug release property, and CD44 and GM dual-targeted capacities, have the potential for further application in the treatment of colitis.
研究领域:
药学
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生物技术
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纳米技术
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胃肠病学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2019
·
IF 0
Beibei Lu,Zhourui Xiao,Zhenyuan Wang,Binshen Wang,Weiwei Zhao,Xing Ma,Jiaheng Zhang
Redox-responsive ferrocene (Fc)-grafted supramolecular block copolymers functionalized with hyaluronic acid (HA-g-β-CD/Fc-polymers or HAP) or folic acid (FA-g-β-CD/Fc-polymers or FAP) were synthesized by host–guest interaction. The copolymer structures were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, and gel permeation chromatography. The block copolymers self-assemble into spherical micellar aggregates in aqueous solution, and exhibit reversible redox characteristics in the presence of an oxidant and reductant. The tunable redox response was evaluated by transmission electron microscopy, ultraviolet–visible spectroscopy, cyclic voltammetry and dynamic light scattering. The micelles rapidly release DOX under oxidative and acidic condition in vitro. Furthermore, presence of HA and FA on the micelles enabled effective uptake by the CD44 and FA receptor-overexpressing cancer cells. Taken together, the redox responsive Fc-block copolymer micelles have good biocompatibility, biodegradability, low toxicity, and high selectivity, and are a highly promising drug delivery system for cancer therapy.
研究领域:
药学
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材料科学
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纳米技术
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癌症研究
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产品关联
DOI
PubMed
Acta Biomaterialia
·
2017
·
IF 6.319
Yang Fan,Qingjie Wang,Guimei Lin,Yanbin Shi,Zili Gu,Tingting Ding
In this study, novel prodrug-modified cationic liposome nanocomplexes (Combo NCs) were reported for gemcitabine (GEM) and docetaxel (DTX) co-delivery. This nanoplatform exhibited multiple favorable characteristics, such as a ‘green’ fabrication with a one-step chemical reaction, appropriate size (∼200 nm) and distribution (PDI < 0.2), low zeta potential (−31.1 mv), high drug-loading efficiency (9.3% GEM plus 3.1% DTX, wt%) and pH and enzymatic dual-stimulus-responsive release properties. Immunofluorescence and cellular uptake studies showed that Combo NCs efficiently targeted overexpressed CD44 in MDA-MB-231 carcinoma. In vitro studies revealed that Combo NCs played a critical role in the synergistic induction of cytotoxicity, apoptosis and inhibition of wound healing. Combo NCs were confirmed to exhibit great potency for increasing S phase arrest and remodeling the CDA and dCK balance by decreasing the mRNA expression of CDA down to 0.09-fold and increasing the mRNA expression of dCK by 1.36-fold, remarkably increasing the dCK/CDA ratio to 15.3-fold compared with the blank control. The biodistribution results obtained in vivo revealed an effective accumulation in tumor foci. All of these advantages of Combo NCs contributed to their remarkable anti-tumor efficacy without systemic toxicity as well as their apoptosis-enhancing and anti-proliferative capacities, as determined by TUNEL and Ki67 immunohistochemistry in vivo . Consequently, such a rationally contemplated co-delivery system demonstrated the promising potential of clinical applications for triple-negative breast cancer therapy. State of Significance The Combo NCs were innovatively applied for co-delivery of hydrophilic GEM and hydrophobic DTX. The ester bond linking and shielding effect of HA-GEM made the carriers achieve synchronous release properties, which was determined in in vitro release study. Due to the HA modification, the vectors own great potency for positive targeting to CD44 overexpressed triple-negative breast cancer cells MDA-MB-231. Cytotoxicity and apoptosis studies confirmed the targeting effect and synergism between two drugs. Interestingly, we found in cell cycle study, drug combinations (free combination or Combo NCs) didn’t show a rise in G2M phase, which was significantly higher when treated DTX alone. We further discovered the role of DTX in combinations may involve in modulating GEM associated enzymes thus enhancing the efficacy of GEM. Consequently, this nanoplatform provided a novel solution for achieving targeted co-delivery and potentiating effect in cancer therapy.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2026
·
IF 6.1
Songbai Tian,Xin Tang,Saijun Zhang,Yuexin Yao,Ran Bi,Haixia Li,Xiaoming Sun,Zhuo Chen
Digital immunoassay allows for the detection of proteins at fg/mL levels by leveraging the principles of Poisson distribution. Nevertheless, the inherent Poisson noise restricts digital sensitivity to targets exceeding 100 molecules, rendering standard digital assays incapable of detecting targets below this threshold. To overcome this constraint, we introduce an integrated CRISPR/Cas12a-digital immunoassay technology. In this system, the CRISPR/Cas12a machinery first acts as a molecular amplifier, converting each target protein into multiple enzymatic reporters. These enzyme molecules are then individually quantified via a digitized readout system, enabling ultrasensitive protein detection. By harnessing the catalytic amplification of CRISPR/Cas12a, the method achieves detection of proteins at copy numbers below 100, effectively surpassing the conventional sensitivity barrier of digital immunoassays. We validated this approach through highly selective and accurate detection of CD44 protein. A linear response was observed across a concentration range of 0.05 to 5 fg/mL, conforming to the calibration model: P(X > 0) = 0.1191c + 0.0036. The limit of detection was determined to be 0.018 fg/mL, equivalent to approximately 36 molecules of CD44. The method was further applied to quantify CD44 in plasma samples from colorectal cancer patients, demonstrating its strong potential for clinical use in early cancer diagnosis and treatment monitoring.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2023
·
IF 4.6
Xiaohui Tang,Munire Kurban,Ipargul Hafiz,Qi Shen,Mei Wang
Aims To prepare hyaluronic acid-loaded Harmine polymeric micelles with CD 44 targeting properties and to investigate their anti-breast cancer effects in vitro . Methods The carboxyl group on hyaluronic acid is coupled to the amino group on 3,5-bis(trifluoromethyl)benzylamine by an amidation reaction. And the polymeric micelles self-assemble to encapsulate the Harmine in a hydrophobic core, characterized the polymer micelles by IR, 19 F-NMR, Malvern particle sizing, release, hemolysis, and other experiments. Used CD 44 -positive MDA-MB-231 cells and CD 44 -negative MCF-7 cells as tumor models. The effect of polymer micelles on breast cancer cells in vitro by cytotoxicity assay, confocal, and flow cytometry. Results The prepared polymer micelles had a uniform particle size of about 200 nm, good dispersion, PDI < 0.3, encapsulation rate up to 87%, drug loading of 4.12±0.03%, and negative charge. Hyaluronidase has a good enzymatic effect on polymeric micelles, with a hemolysis rate of less than 1%. It showed some dose-dependent toxicity to both MDA-MB-231 and MCF-7, with increased uptake of polymer micelles by CD 44 -positive MDA-MB-231 compared to CD 44 -negative MCF-7 cells and significant effects of polymer micelles on apoptosis and cycling in both cell types. These results suggest that the hyaluronic acid-loaded Harmine polymer micelles designed in this study are effective in killing breast cancer cells while at the same time reducing the toxicity of Harmine and improving its slow-release targeting.
研究领域:
药剂学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2023
·Vol. 19
·期 12
·2045-2059
·
IF 2.9
Yang Bowen,Huang Luyao,Zhou Zishuo,Yin Shanmei,Xi Mingrong
We aimed to develop an ovarian cancer-directed drug delivery system based on the high affinity of hyaluronic acid for CD44. The effects and mechanisms of hyaluronic acid-containing nanoparticles were investigated. The expression of CD44 in ovarian cancer was also determined. Hyaluronic
acid polymerized nanoparticles (HANPs), FITC-HANPs, and paclitaxel (PTX)-HANPs were prepared, and their characteristics were evaluated. The in vitro targetability and cytotoxicity properties of PTX-HANPs were evaluated through in vitro drug uptake and cytotoxicity assays. The
mechanisms of PTX-HANPs activity were investigated by apoptosis, wound healing, and Transwell invasion assays. In vivo targeting properties of HANPs were observed using a mouse ID8 subcutaneous model. in vitro experiments revealed an improved uptake of FITC-HANPs. The cytotoxicity
of PTX-HANPs in A2780/CP70 and ID8 cells was higher than that of PTX alone. PTX-HANPs increased cell apoptosis in a dose-dependent manner and exhibited a similar ability as PTX to inhibit cell migration. Furthermore, HANPs did not promote A2780/CP70 or ID8 cell migration and showed limited
inhibitory effects on their invasion. In vivo drug tracing experiments demonstrated the targetability of FITC-HANPs. In conclusion, PTX-HANPs improved PTX targetability and exhibited potent tumor-specific therapeutic activities. It may be considered a promising formulation for the preclinical
development of agents targeting epithelial ovarian cancer.
研究领域:
药剂学
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肿瘤学
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生物医学工程
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）