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
✓ 已验证
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
✓ 已验证
产品关联
DOI
PubMed
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
✓ 已验证
产品关联
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
✓ 已验证
产品关联
DOI
高影响因子
Materials Today
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2025
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IF 22
Muchao Chen,Yi Yu,Jiaying Hu,Yi-Chi Wang,Dongxu Zhao,Zhaoxin Ji,Lin Xu,Qiang Zhang,Baoye Ma,Yi Liu,Caifang Ni,Lin Gu,Youyong Li,Zhuang Liu,Yang Yang,Qian Chen
Hepatic arterial infusion chemotherapy (HAIC) delivers high local drug concentrations for hepatoma treatment but faces challenges such as catheter-related complications and systemic toxicity. To address these, we developed Mel-gel, an ultrasound-driven hydrogel system formed entirely by the chemotherapeutic agent Melphalan (Mel) without chemical modifications. Under ultrasound, Mel transitions from spherical to worm-like aggregates, rapidly forming a nanofiber-based hydrogel through non-covalent interactions. This innovative system offers sustained drug release, excellent bioavailability, and improved biosafety profiles. Mel-gel enables expedited catheter removal, reduces systemic toxicity, enhances local drug concentration, and prolongs drug-cell interaction time. Compared to conventional HAIC systems, Mel-gel’s unique in situ formation maximizes drug delivery and achieves superior targeting within complex vascular structures. In a rat orthotopic hepatoma model, Mel-gel-assisted HAIC demonstrated remarkable therapeutic efficacy, achieving a tumor inhibition rate of 98.09%, activating anti-tumor immune responses, and curing 60% of treated rats. This novel ultrasound-responsive hydrogel represents a promising advancement in hepatoma treatment, offering enhanced precision, efficacy, and safety. Additionally, Mel-gel’s versatile drug delivery capabilities may enhance the pharmacokinetics of various drugs and support synergistic therapies. This novel hydrogel system offers a promising advancement in hepatoma treatment, aiming to optimize outcomes and expand its application to other therapeutic agents.
研究领域:
肿瘤学
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药物递送
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纳米医学
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生物医学工程
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癌症治疗
✓ 已验证
产品关联
DOI
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
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）