INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2026
·
IF 6
Chunpeng Yang,Mengdi Wu,Min Li,Wenbin Niu,Yinan Zhao,Shubiao Zhang
MST and CD quantitatively confirmed that the flexible ADH-DTDPA spacer preserves strong CD44 binding ( K D = 15.3 μM). • HPMs showed pH/redox-triggered release, with 78.2% payload release in 72 h under tumor-mimicking conditions. • HPMs achieved superior antitumor efficacy at a lower dose while reducing systemic toxicity in vivo . Clinical application of podophyllotoxin (PPT) is significantly hampered by poor aqueous solubility and considerable systemic toxicity. Herein, we engineered dual-targeting and dual-cleavable prodrug micelles (HPMs) by conjugating PPT to hyaluronic acid (HA) backbone via a flexible, dual-responsive spacer, adipic dihydrazide–3,3′-dithiodipropionic acid (ADH-DTDPA). In vitro , HPMs demonstrated efficient CD44-mediated internalization in NCI-H1299 cells and rapidly disassembled under tumor microenvironment (TME) conditions (pH 5.0/GSH). Crucially, microscale thermophoresis (MST) provided quantitative evidence of the targeting mechanism, revealing a high binding affinity ( K D = 15.3 μM) for the CD44 receptor. In vivo , this design achieved effective accumulation of the micelles at tumor sites. Notably, HPMs (10 mg/kg) achieved superior tumor inhibition compared to free PPT (15 mg/kg) without inducing hepatotoxicity or nephrotoxicity. These findings provide a safe delivery strategy to overcome the clinical limitations of PPT and offer quantitative molecular insights into the rational design of targeted nanomedicines for lung cancer therapy. Download: Download high-res image (244KB) Download: Download full-size image
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Wenhao Ding,Fengzhi Qiao,Shichao Xuan,Meijun Liu,Fan Yang,Cristabelle De Souza,Guanhua Xuan,Peng Lei,Huaxi Yi,Lanwei Zhang,Hong Jiang,Xiangzhao Mao,Kai Lin
Probiotic delivery faces challenges in maintaining bacterial viability and achieving precise targeting of the gastrointestinal tract. In this study, alginate microspheres (ALG MSs) encapsulating Clostridium butyricum (CB) were fabricated using electrospray technology. Hyaluronic acid (HA) was used to modify both the microspheres and the CB surface to enable targeted delivery through the receptor–ligand interaction between HA and CD44. The resulting CBHA@ALGHA MSs exhibited an encapsulation efficiency of 69.23 ± 7.30% and a postdigestion survival rate of 94.56 ± 4.87%. HA modification enhanced adhesion to inflamed Caco-2 cells by 2.7- and 2.3-fold for microspheres and CB, respectively. In vivo fluorescence imaging confirmed a 1.7-fold increase in targeted accumulation at CD44-overexpressing inflamed colonic sites. Oral administration of CBHA@ALGHA MSs alleviated DSS-induced colitis, elevated short-chain fatty acids, restored barrier integrity, and improved gut microbial balance. This strategy ensures probiotic viability and enables inflammation-targeted colonic delivery for advanced probiotic applications.
研究领域:
制药技术
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药物递送系统
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微生物学
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生物医学工程
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胃肠病学
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CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Haitong Wen,Yanan Du,Weiqin Wang,Zhihao Zhang,Anqing Zheng,Md. Fardin Khan,YuTong Lu,Huixia Lv
CD44 and TRPV1 are confirmed to be upregulated in the inflamed skin of atopic dermatitis models. • The dual-targeted VHC carrier enhances intradermal drug retention and residence time. • Cur/VHC achieves selective cytotoxicity in inflamed keratinocytes via dual-receptor targeting. • VHC acts as a competitive TRPV1 antagonist, demonstrating anti-pruritic efficacy in vivo . • Cur/VHC integrates antipruritic, anti-inflammatory, and barrier-repair functions in ISDs. Inflammatory skin diseases (ISDs) involve a vicious cycle of inflammation, pruritus, and tissue damage, posing a persistent therapeutic challenge. To interrupt this cycle, a multifunctional amphiphilic polymer (VHC) is engineered by conjugating hyaluronic acid with octadecylamine and vanillyl alcohol, forming a dual-targeting transdermal nanocarrier. VHC markedly enhances intradermal retention (3.4-fold vs. free Cur at 4 h) and cellular uptake (185-fold vs. free C 6 ) by anchoring to CD44 and TRPV1 receptors, while simultaneously inhibiting TRPV1 activation and expression, a central mediator of itch signaling, to alleviate pruritus. Benefiting from its amphiphilic structure, VHC also functions as an efficient carrier for poorly soluble drugs, broadening its therapeutic scope. Encapsulation of the anti-inflammatory agent curcumin (Cur) yields Cur/VHC micelles (~240 nm) with sustained release under mildly acidic conditions. Because CD44 and TRPV1 are overexpressed under inflammatory conditions, Cur/VHC preferentially accumulates in TNF-α-stimulated HaCaT cells, suppresses pathological proliferation, and mitigates oxidative stress. In an atopic dermatitis mouse model, topical VHC and Cur/VHC accelerate inflammation resolution, normalize epidermal architecture, restore barrier proteins (K10 and filaggrin), relieve itch (by reducing IL-31, IgE, and tachykinin precursor 1), promote hair follicle regeneration, and reduce mast cell degranulation. By integrating receptor targeting, TRPV1 inhibition, and anti-inflammatory delivery, VHC offers a multimodal therapeutic platform for ISDs. Scheme 1. Therapeutic effects of VHC and Cur/VHC. By dually targeting CD44 and TRPV1, VHC and Cur-VHC enhance intradermal drug retention, thereby producing anti-inflammatory, antipruritic, and skin-repair effects for the treatment of inflammatory skin diseases. Download: Download high-res image (422KB) Download: Download full-size image
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NANOTECHNOLOGY
·
2025
·Vol. 36
·期 12
·125102
·
IF 2.8
Yanping Wang,Peiyan Qi,Shenbao Shi,Cong Pang,Weijie Wang,Dazhao Fang
Glioblastoma (GBM) is a malignant tumor with highly heterogeneous and invasive characteristics leading to a poor prognosis. The CD44 molecule, which is highly expressed in GBM, has emerged as a highly sought-after biological marker. Therapeutic strategies targeting the cell membrane protein CD44 have emerged, demonstrating novel therapeutic potential. In this study, we constructed a nanodrug system (HA-Liposome@Dox) based on hyaluronic acid-engineered liposomes delivering adriamycin to target GBM. The system efficiently encapsulated Dox inside the liposomes through a hydrophilic-hydrophobic interaction mechanism, and the resulting HA-Liposome@Dox exhibited excellent loading efficacy, attributed to its uniform particle size distribution and negatively charged surface. Further evaluation revealed that HA-Liposome@Dox possessed excellent stability and safety and could promote the effective uptake of drug particles by CD44-overexpressing tumor cells, thus exerting a more potent cell-killing effect. Notably, in the treatment of GBM, HA-Liposome@Dox demonstrated significantly greater tumor growth inhibition compared to free Dox and prolonged the survival of tumor-bearing mice. Taken together, the present study not only verified the feasibility of HA-Liposome@Dox as an effective therapeutic tool against GBM and other CD44-positively expressing tumors, but also opened a promising new avenue for the clinical treatment of this type of refractory malignancies.
研究领域:
肿瘤学
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药剂学
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分子生物学
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2020
·
IF 2.734
Nan Zhang,Jing Zhang,Baocheng Tian,Keke Li,Baohuan Wu,Jingtian Han
CD44 play a pivotal role in tumor progression and metastasis. Targeting CD44 expressing cells using hyaluronic acid (HA) is a promising approach in the treatment of many types of tumors. Here, CD44-targeted conjugate was introduced by hyaluronic acid-deoxycholic acid (HA-DOCA) through the connection of the ester bond. Hydrophilic drug Gemcitabine (GEM) and hydrophobic DOCA are linked by the amide linkage. The DOCA-GEM was mixed with HA-DOCA to form mixed micelles (MMs) with low critical micelle concentration . Dynamic laser light scattering and transmission electron microscope measurements revealed that HA-DOCA/DOCA-GEM MMs displayed sphericity, with an average diameter of 149 ± 3 nm, and negative zeta potential . Hemolysis and cytotoxicity studies confirmed the safety of the HA-DOCA conjugate. The in vitro drug release was investigated, demonstrating that the intracellular-mimicking microenvironment could accelerated the GEM release of the HA-DOCA/DOCA-GEM MMs. The HA-DOCA/DOCA-GEM MMs showed higher cellular uptake efficiency by MCF-7 cells according to confocal laser scanning microscopy and flow cytometry, therefore achieving much stronger anticancer efficacy than free GEM and DOCA-GEM micelles. Our results suggest that HA-DOCA/DOCA-GEM MMs might be a potential candidate for cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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MICROCHEMICAL JOURNAL
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2025
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IF 5.1
Shiwei Xu,Guofeng Wang,Yueyue Feng,Liying Huang,Zhongyu Yang,Yu Zhang,Jiacheng Dong,Yajun Wang,Nannan Liu
Gastric cancer (GC) is one of the leading causes of cancer-related mortality worldwide. miRNA-106a is a small non-coding RNA that is significantly up-regulated in GC cells. CD44 protein serves as a cell adhesion molecule in GC, and its high expression is associated with tumor invasiveness and metastatic potential. Detection of these two biomarkers for GC can significantly improve the sensitivity and specificity of tests, thus identifying patients more accurately and facilitating early diagnosis and intervention. In this study, we proposed a bottom-up assembly method of silica nanowires (SiNWs) modified glass microtube to construct a glass microsensor based on the functionalization of SiNWs-dual probes (SiNWs@DGM), which can be used for the simultaneous detection of the two gastric cancer markers mentioned above in a highly sensitive and specific manner. The detection limit of the sensor is as low as 1 aM for the target miRNA-106a and 1 pg/mL for CD44 protein. The constructed SiNWs@DGM demonstrates excellent selectivity, high anti-interference ability, specificity, and good storage stability in sample analysis without any amplification. Therefore, our biosensing strategy can reduce false positive and false negative results, providing more reliable support for gastric cancer management and ultimately improving patient prognosis and survival rates.
研究领域:
生物医学工程
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分子诊断学
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Journal of Biomedical Nanotechnology
·
2017
·Vol. 13
·期 11
·1457-1467
·
IF 4.521
Zhu Yuyang,Li Wei,Zhao Xin,Zhou Zhengjie,Wang Yitong,Cheng Yiyun,Huang Quan,Zhang Qiang
Targeted photothermal therapy (PTT) can improve the therapeutic outcomes and reduce side effects in cancer treatment. However, additional functionality means additional synthetic steps, increased risk of toxicity and complex behavior and effects in vivo. Herein, we developed
a one-pot method to prepare tumor-targeted photothermal nanoparticles. Hyaluronic acid (HA), an anionic glycosaminoglycan that targets tumors via overexpressed cluster determinant 44 (CD44), was used as a polymer stabilizer to synthesize HA-encapsulated platinum nanoparticles (HA/Pt). The
in vitro experiments demonstrated that HA/Pt were more efficiently internalized by cancer cells overexpressing CD44 compared with the non-tumor targeting alginate acid-encapsulated Pt nanoparticles (AA/Pt). The in vivo studies revealed that HA/Pt accumulated more in CD44-overexpressing
tumor than AA/Pt, and more efficiently inhibited tumor growth via PTT. Our study developed an innovative method for facile fabrication of tumor-targeting photothermal nanoparticles.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qi Xiong,Yiwu Wang,Jingyuan Wan,Pei Yuan,Huali Chen,Liangke Zhang
In this study, a novel hyaluronic acid-based quercetin nanoformulation (QUT/HA-NF) was constructed for targeted tumor therapy. QUT/HA-NFs have the advantages of simple operation steps, low production cost and good industrialization prospects. Moreover, surfactants, solvents and chemicals are not involved in the preparation process, which avoid the cumbersome extraction of surfactants and the side effects caused by residual solvents or chemicals. The QUT/HA-NFs we prepared have small particle size and high drug loading. In vitro studies have shown that QUT/HA-NFs can significantly enhance tumor cell uptake and tumor cell killing through CD44 receptor mediation. In a xenograft mouse model of 4T1 tumor, QUT/HA-NFs showed stronger inhibition of tumor growth compared with quercetin alone. The QUT/HA-NFs proposed in this study are expected to provide a potential candidate for the treatment of tumors.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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高影响因子
ACS Sensors
·
2022
·
IF 9.618
Meiling Lian,Yuqing Shi,Liuxing Chen,Yongji Qin,Wei Zhang,Jingbo Zhao,Da Chen
The inactive adsorption and interference of biomolecules in electrochemical biosensors is a topic of intense interest. Directly utilizing native cell membranes to endow electrochemical surfaces with antifouling and biocompatible features is a promising strategy, rather than attempting to synthetically replicate complex biological interface properties. In this study, we present a facial and sensitive sandwich-type antifouling immunoassay through platelet membrane/Au nanoparticle/delaminated V2C nanosheet (PM/AuNPs/d-V2C)-modified electrode as the substrate of sensing interface and methylene blue/aminated metal organic framework (MB@NH2-Fe-MOF-Zn) as an electrochemical signal probe. The biosensor perfectly integrates the high conductivity of AuNPs-loaded V2C MXene with the excellent loading property of NH2-Fe-MOF-Zn to improve the electrochemical sensing performance. In addition, the excellent antifouling properties of the homogeneous cell membrane can effectively prevent the non-specific adsorption of model proteins. The obtained antifouling biosensor possesses the capability of ultrasensitive detection of CD44 and CD44-positive cancer cell in complex liquids and exhibits good analytical performance for the analysis of CD44 with a linear range from 0.5 ng/mL to 500 ng/mL. This strategy of developing cell membrane-based biosensing systems with enhanced antifouling capability can be easily expanded to the construction of other complex biosensors, and the advanced biological probes and analytical methods provide a favorable means to accurately quantify biomarkers associated with tumor progression.
研究领域:
生物化学
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生物技术
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材料科学
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分析化学
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癌症研究
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高影响因子
CARBOHYDRATE POLYMERS
·
2018
·
IF 5.158
Jing-Bo Hu,Shu-Juan Li,Xu-Qi Kang,Jing Qi,Jia-Hui Wu,Xiao-Juan Wang,Xiao-Ling Xu,Xiao-Ying Ying,Sai-Ping Jiang,Jian You,Yong-Zhong Du
Based on the abnormally increased expression of CD44 receptors on renal tubule epithelial cells during ischemia/reperfusion-induced acute kidney injury (AKI), we developed a hyaluronic acid-curcumin (HA-CUR) polymeric prodrug targeting to epithelial cells and then relieving oxidative stress damages. The water solubility of HA-CUR was significantly enhanced and approximately 27-fold higher than that of CUR. Cellular uptake test showed HA-CUR was preferably internalized by H 2 O 2 -pretreated tubular epithelial (HK-2) cells compared with free CUR benefiting from the specific binding between HA and CD44 receptors. Biodistribution results further demonstrated the increased accumulation of HA-CUR in kidneys with 13.9-fold higher than that of free CUR. Pharmacodynamic studies indicated HA-CUR effectively ameliorated AKI, and the exact mechanism was that HA-CUR protected renal tubule epithelial cells from oxidative stress damage via inhibiting PtdIns3K-AKT-mTOR signaling pathway. Taken together, this study provides a new therapeutic strategy for the treatment of AKI based on the pathogenesis of the disease.
研究领域:
药理学
·
肾病学
·
药物递送系统
·
分子生物学
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高影响因子
Nano Today
·
2026
·
IF 10.9
Tianwei Lan,Xiaoping Guo,Chang Liu,Pai Wang,Shichen Zhang,Lei Guo,Siyuan Wang,Lu Wang,Rui Zhou,Xinran Yan,Baiqiao Chen,Mujie Kan,Fang Wang,Caina Xu
Allergic asthma (AAS) is a chronic inflammatory airway disease. While zileuton (ZIL) has the efficient ability to relieve AAS symptoms, its systemic, untargeted administration could lead to adverse neurological effects. Thus, we constructed a drug combination nanomicelle (NMs) platform, H(BZP)-NMs, to reach synergistic effect therapy. It was comprised of a hydrophilic end formed from methoxy poly(ethylene glycol) (mPEG) and poly( L -glutamic acid) (PGlu), and a ROS/pH dual-sensitive hydrophobic core. The core was created by coupling 4-(hydroxymethyl)phenylboronic acid (HPBA) to betamethasone (BMZ). Zileuton (ZIL) was strategically loaded in the core. Hyaluronic acid (HA) functionalization further enabled CD44-targeting ability. In pathological microenvironments, the boronate ester bonds undergo responsive cleavage, causing the parallel delivery of the drugs. The slow-release profile addressed the need for rapid early-stage control and prolonged late-stage relief. In vivo, H(BZP)-NMs significantly decreased Penh values, lowered the IL-4, IL-5, IL-13, and LTB4 levels, and ameliorated airway pathological injuries. Given the molecular docking and verification of network pharmacology, these effects were associated with the dual-drug synergistic inhibition of the TLR4-MyD88-NF-κB p65 signals. Collectively, this study shows that H(BZP)-NMs are an inventive nanomedicine approach that unifies targeted delivery and extended co-release, offering promise for accurate and synergistic treatment of AAS.
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eLife
·
2019
·
IF 7.551
Xuefei Yan,Beibei Tang,Biao Chen,Yongli Shan,Huajun Yang,Reproducibility Project: Cancer Biology,Elizabeth Iorns,Rachel Tsui,Alexandria Denis,Nicole Perfito,Timothy M Errington
As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Li et al., 2015), that described how we intended to replicate selected experiments from the paper ‘The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44’ (Liu et al., 2011). Here we report the results. We found the microRNA, miR-34a, was expressed at twice the level in CD44+ prostate cancer cells purified from xenograft tumors (LAPC4 cells) compared to CD44- LAPC4 cells, whereas the original study reported miR-34a was underexpressed in CD44+ LAPC4 cells (Figure 1B; Liu et al., 2011). When LAPC4 cells engineered to express miR-34a were injected into mice, we did not observe changes in tumor growth or CD44 expression; however, unexpectedly miR-34a expression was lost in vivo. In the original study, LAPC4 cells expressing miR-34a had a statistically significant reduction in tumor regeneration and reduced CD44 expression compared to control (Figure 4A and Supplemental Figures 4A,B and 5C; Liu et al., 2011). Furthermore, when we tested if miR-34a regulated CD44 through binding sites in the 3’UTR we did not find a statistically significant difference, whereas the original study reported miR-34a decreased CD44 expression that was partially abrogated by mutation of the binding sites in the CD44 3’UTR (Figure 4D; Liu et al., 2011). Finally, where possible, we report meta-analyses for each result.
研究领域:
肿瘤学
·
分子生物学
·
癌症生物学
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PubMed
高影响因子
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