Frontiers in Chemistry
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2020
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IF 3.693
Ai Qiushuang,Fu Qiang,Liang Feng
Recognition tunneling technique owns the capability for investigating and characterizing molecules at single molecule level. Here, we investigated the conductance value of cucurbit[7]uril (CB[7]) and melphalan@CB[7] (Mel@CB[7]) complex molecular junctions by using recognition tunneling technique. The conductances of CB[7] and Mel@CB[7] with different pH values were studied in aqueous media as well as organic solvent. Both pH value and guest molecule have an impact on the conductance of CB[7] molecular junction. The conductances of CB[7] and Mel@CB[7] both showed slightly difference on the conductance under different measurement systems. This work extends the molecular conductance measurement to aqueous media and provides new insights of pH-responsive host-guest system for single molecule detection through electrical measurements.
研究领域:
生物物理学
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纳米科学
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分子电子学
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PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2026
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IF 9.6
Siyu Shuai,Zhaoxin Ji,Qiang Zhang,Yu Miao,Baoye Ma,Jingjing Shen,Haibin Zhao,Yuan Fang,Zhuyu Hou,Muchao Chen,Xianglei Wu,Qian Chen,Yang Yang
Chemotherapy, a cornerstone in cancer treatment, faces significant challenges including inadequate drug targeting and tumor microenvironment limitations. Herein, we developed a small molecule self-assembled hydrogel loaded with nitric oxide (NO) donors S-nitrosoglutathione (GSNO) and chemotherapy drug Melphalan (Mel), termed GSNO-Mel hydrogel (GM Gel) by leveraging the unique property of Mel, self-assembled into hydrogels under ultrasonic conditions. Importantly, the sustained co-released of NO and Mel demonstrated synergistic therapeutic effects, not only inducing apoptosis and cell cycle arrest but also triggering a more potent immunogenic cell death (ICD), which may be attributed to NO's potential to reverse Mel-induced multidrug resistance in tumor cells, thereby significantly improving tumor-killing efficacy. The subsequent release of damage-associated molecular patterns (DAMPs) further amplified the immune response by activating dendritic cells. Additionally, NO played a critical role in remodeling the tumor microenvironment by polarizing tumor-associated macrophage toward M1 phenotype and alleviating hypoxia. Notably, the GM Gel system significantly suppressed tumor growth while eliciting anti-tumor immunity, highlighting its potential as a multifaceted therapeutic strategy for cancer treatment. Consequently, this work develops a facile strategy for engineering NO donor-integrated self-assembling hydrogels based on chemotherapeutic drugs, offering a promising approach to achieve chemoimmunotherapy through multiple mechanisms. Download: Download high-res image (163KB) Download: Download full-size image
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DOI
PubMed
高影响因子
BIOMATERIALS
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2022
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IF 15.304
Kuan Jiang,Xingyan Fan,Yang Hu,Shengyu Yao,Yu Liu,Changyou Zhan,Weiyue Lu,Gang Wei
Retinoblastoma is the most common primary intraocular malignancy in infancy with a metastases-related death risk. However, a safe and convenient treatment without enucleation is still an unmet clinical need. In this work, a cell-penetrating peptide, 89WP, was conjugated with melphalan (89WP-Mel), which achieved high tumor inhibition effects as intravitreally injected melphalan via topical instillation for the first time. Notably, the “outside-in” diffusion of instilled 89WP-Mel created a protective shield surrounding the eye, efficiently preventing tumor metastases, while the mice treated with intravitreally injected melphalan suffered more brain metastases related death. The ocular absorption of 89WP-conjugated melphalan and other small molecules , both hydrophobic and hydrophilic , occurred via non-corneal pathway with high safety and a prolonged residence duration in retina up to 24 h. The present work paves a new avenue for simultaneous intraocular tumor inhibition and extraocular metastases prevention in a safe and convenient way via topical instillation.
研究领域:
肿瘤学
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药理学
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眼科
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2019
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IF 4.784
Jia Li,Jihong Wang,Xuetong Zhang,Xin Xia,Chenchen Zhang
Melphalan (MEL) is an effective chemotherapeutic agent for treatment of retinoblastoma (Rb) which is the most common childhood malignancy. However, the inherent cardiopulmonary toxicity and hazardous integration limit its therapeutic effect on RB. N -Acetylheparosan (AH), a natural heparin-like polysaccharide in mammals with long circulation effect and good biocompatibility, was linked by d-α-tocopherol acid succinate (VES) via and cystamine (CYS) to synthesize reduction-responsive N -acetylheparosan-CYS-Vitamin E succinate (AHV) copolymers. In addition, CYS was replaced by adipic acid dihydrazide (ADH) to obtain a control of non-reduction-responsive polymers N -acetylheparosan-ADH-Vitamin E succinate (ADV). MEL-loaded AHV micelles (MEL/AHV) as well as ADV micelles (MEL/ADV) were prepared with small particle size and high drug loading content. In vitro drug release showed that MEL/AHV micelles presented obvious reduction-triggered release behavior compared with MEL/ADV. In vitro antitumor effects were investigated using WERI-Rb-1 retinoblastoma cells. Cytotoxicity experiments showed that the IC 50 of MEL/AHV was significantly lower than that of free MEL and MEL/ADV, suggesting that MEL/AHV enhanced the cytotoxicity against retinoblastoma cells. Furthermore, MEL/AHV micelles were more easily uptaken by multiple pathways compared with MEL/ADV and free MEL. Therefore, MEL/AHV might be a potential delivery system for enhanced delivery of melphalan to Rb cells.
研究领域:
肿瘤学
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药剂学
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生物材料
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2013
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IF 3.479
Bo Lu,Dan Huang,Hua Zheng,Zhijun Huang,Peihu Xu,Haixing Xu,Yihua Yin,Xia Liu,Dan Li,Xueqiong Zhang
A series of melphalan-O-carboxymethyl chitosan (Mel-OCM-chitosan) conjugates with different spacers were prepared and structurally characterized. All conjugates showed satisfactory water-solubility (160-217 times of Mel solubility). In vitro drug release behaviors by both chemical and enzymatic hydrolysis were investigated. The prodrugs released Mel rapidly within papain and lysosomal enzymes of about 40–75%, while released only about 4–5% in buffer and plasma, which suggested that the conjugates have good plasma stability and the hydrolysis in both papain and lysosomes occurs mostly via enzymolysis. It was found that the spacers have important effect on the drug content, water solubility, drug release properties and cytotoxicity of Mel-OCM-chitosan conjugates. Cytotoxicity studies by MTT assay demonstrated that these conjugates had 52–70% of cytotoxicity against RPMI8226 cells in vitro as compared with free Mel, indicating the conjugates did not lose anti-cancer activity of Mel. Overall these studies indicated Mel-OCM-chitosan conjugates as potential prodrugs for cancer treatment.
研究领域:
药学
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肿瘤学
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DOI
PubMed
高影响因子
Nano Today
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2021
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IF 20.722
Xinyu Zhang,Xiao Duan,Yueying Hu,Zhongmin Tang,Congxiu Miao,Wei Tao,Jun Wu
The clinical applications of polymer-based nanomedicines have been restricted by their complicated synthesis processes, biosafety issues, and uncontrollable drug loading. In this study, we developed a peptide-like polydrug for cancer chemotherapy using the FDA-approved drug melphalan via a simple one-step synthesis strategy. The prepared poly (melphalan) (PMP)-PEG was characterized through standard methods and formulated into sub-100 nm nanoparticles using the nanoprecipitation method. The poly (melphalan)-PEG nanoparticles (PMP NPs) showed controllable drug loading (up to 70 wt%) with high stability in buffers. In vitro cell viability studies showed good cell uptake behavior and high cytotoxicity of the PMP-NPs compared to Evomela controls (a commercial and clinical melphalan formulation). For in vivo mouse models tests, the PMP-NPs could accumulate in the tumor sites for ≥ 1 week and effectively inhibited tumor growth with minimal side-effects. This peptide synthesis strategy and a melphalan based polydrug nanoplatform may be promising for new drug development and effective cancer therapy.
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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药物递送系统
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产品关联
DOI
高影响因子
Acta Pharmaceutica Sinica B
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2025
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IF 14.6
Guoqing Wang,Kai Wu,Zongliang Zhang,Yongdong Chen,Yanfang Li,Xiaoshuang Jiang,Licong Liang,Yiliu Yang,Hongsong Fan,Jing Sun,Aiping Tong,Fang Lu
Retinoblastoma (RB) is the most common primary ocular malignancy in children, arising from the developing retina. While higher doses of local chemotherapy have improved tumor control, concerns regarding retinal toxicity and the development of chemoresistance remain significant. Oncolytic adenovirus (OA) presents a promising therapeutic approach for RB, but rapid clearance often limits its therapeutic effects. In this study, we engineered a genetically modified OA derived from human adenovirus 5 (Ad5), designed to selectively target and lyse RB cells. The combination of OA with low-dose melphalan demonstrates an enhanced antitumor effect, while minimizing retinal toxicity. In vitro and in vivo experiments demonstrated that melphalan significantly enhanced the antitumor effect of OA and extended ocular survival. More importantly, we developed a biocompatible injectable hydrogel delivery system based on the covalent coupling of collagen and aldehyde-modified cyclodextrin, which effectively enhances the loading efficiency of melphalan and enables sustained co-delivery of OA and melphalan. The mouse RB tumor model confirmed that this hydrogel system (OA-Mel@CCA) achieved localized and sustained delivery of both therapeutics, effectively controlling tumor growth and preventing brain metastasis. Additionally, retinal structure and function were notably preserved in mice treated with OA-Mel@CCA, with no observed retinal toxicity. These findings suggest that the injectable hydrogel-based co-delivery of melphalan and oncolytic adenovirus could represent a promising strategy for RB treatment.
研究领域:
肿瘤学
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眼科
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纳米医学
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药物递送
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基因治疗
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转化医学
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生物材料
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产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
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2019
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IF 3.621
Jie Wu,Ximing Tian,Yihua Yin,Meng He,Weiquan Cai,Guanghua He,Wenjin Xu,Yue Dai,Jiahao Mai,Mengqi Gan,Fengxinjia Zhang
To improve hydrolytic stability and biological half-life and anticancer efficacy of the anti-cancer drug melphalan (Mel), a novel esterification strategy was developed to fabricate a pH/enzyme dual-responsive polymer prodrug (mPEG-Mel) via the formation of an ion bond between the carboxyl group in Mel and diazotized p-aminobenzoate-terminated poly(ethylene glycol) monomethyl ether (mPEG-N 2 + ) followed by light-induced conversion of the ionic bond to an ester bond. The prodrug could self-assemble into nanoparticles. Under physiological conditions (pH 7.4), the nanoparticles exhibited a regular core-shell structure with about 100 nm, which could effectively inhibit the hydrolysis of pharmacophores in Mel structure and showed the long-circulation ability. While pH dropped to 5.0, an obvious increase in the nanoparticle size was observed and enhanced by different concentrations of cathepsin B (CTB), reaching a diameter of 675 nm or more in the presence of 2.0 µg/mL CTB. The nanoparticles showed minimal drug release at pH 7.4 (less than 10% in 24 h); however, drug release could be significantly accelerated in a CTB-containing medium at pH 5.0. Cell experiments showed that the half-inhibitory concentration (IC50) of nanoparticles was 1.00 µg/mL, which was about 5 times lower than that of free Mel (5.00 µg/mL), and indicating that the nanoparticles were more cytotoxic to cancer cells (4T1 cells). However, significantly reduced cytostatic effects were observed for normal cells (3T3 cells). In addition, cell uptake observation further supported the above experimental results, a stronger red fluorescence in 4T1 cells was observed for NR-loaded nanoparticles, which meant that the nanoparticles could release drug in response to pH/enzyme stimulation. Thus, mPEG-Mel based pH/enzyme double-response polymer prodrug nanoparticles could effectively enhance drug stability and anticancer 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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药物递送系统
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DOI
高影响因子
危险品化学品经营许可证（带存储）