JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS
·
2019
·
IF 1.976
Yumeng Yang,Shixin Liu,Xiang Cai,Dong Ma,Jun Xu
To obtain an efficient drug and gene co-delivery hydrogel, methoxy polyethylene glycol was reacted with the caprolactone units to form the MPEG-PCL block copolymer through the polymerization reaction, which is amphiphilic and can load the hydrophobic drugs. Then, MPEG-PCL conjugated with a multi-generation poly(L-lysine) dendron to form the guest molecule MPEG-PCL-PLLD. After interacted with α-cyclodextrin through host–guest inclusion, the drug and gene dual carrier of supramolecular hydrogel was obtained. The physical properties of the hydrogel, such as the gelation time, the hydrogel strength, or its shear viscosity, could be modulated by the hose molecule of α-cyclodextrin content. MPEG-PCL-PLLD could co-load the drug and gene effectively. After gelation, the loaded drug and gene could be released sustainedly, and the release rate of them was also modulated by the α-cyclodextrin content. The supramolecular hydrogel showed a sustained effect on tumor cells and could induce the cell apoptosis sustainedly. Moreover, the co-delivery strategy was superior to only drug or gene used in tumor cell inhibition. This supramolecular hydrogel as the high-efficiency and sustained co-delivery system showed a promising application in a long-term tumor therapy.
研究领域:
生物材料学
·
肿瘤治疗学
·
药剂学
✓ 已验证
DOI
高影响因子
Advanced Therapeutics
·
2023
·Vol. 6
·期 7
·2200356
·
IF 4.6
Haixia Liu,Xianxian Yao,Weichu Zhu,Jiaxin Zhang,Shuangping Ma,Daru Lu,Wuli Yang
Colorectal cancer is one of the most common causes of cancer-related deaths worldwide. Ferroptosis is a non-apoptotic form of regulated cell death that can be triggered by excessive lipid peroxidation and provides an alternative cancer treatment option. To design ferroptosis-targeted nanomedicine, a new type of nanoparticle is synthesized. The antineoplastic agent simvastatin (SIM) and specifically designed short hairpin RNA (shRNA) are co-loaded into zeolitic imidazolate framework-8 (ZIF-8) nanoparticles coated with poly(carboxybetaine methacrylate) (PCBMA). The constructed shRNA/ZIF-8@PCBMA-SIM nanoparticles effectively eliminate human colorectal carcinoma cells in vivo, showing superior cytotoxicity against tumors owing to their improved targeting ability and the high retention of antineoplastic agents delivered at tumor sites. Furthermore, SIM and shRNA downregulate the expression of ferroptosis-related enzymes 3-hydroxy-3-methylglutaryl-CoA reductase and glutathione peroxidase 4, thus, triggering ferroptosis in cancer cells. Given that SIM is already approved for clinical use, and shRNA offers high potency to downregulate the cystine/glutamate antiporter (x-CT) system protein (subunit SLC7A11), shRNA/ZIF-8@PCBMA-SIM nanoparticles show great clinical potential to treat colorectal cancer via ferroptosis. This presents an alternative therapy that addresses the limitations of chemotherapy.
研究领域:
肿瘤学
·
纳米技术
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药学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Chemistry
·
2021
·
IF 5.221
Wang Weicai,Liu Xiaofan,Ding Lairong,Jin Hyung Jong,Li Xuemei
Hypoxia is not only the reason of tumor metastasis but also enhances the spread of cancer cells from the original tumor site, which results in cancer recurrence. Herein, we developed a self-assembled RNA hydrogel that efficiently delivered synergistic DNA CpG and short hairpin RNA (shRNA) adjuvants, as well as MnO2 loaded-photodynamic agent chlorine e6 (MnO2@Ce6), and a chemotherapy drug doxorubicin (DOX) into MDA-MB-231cells. The RNA hydrogel consists of one tumour suppressor miRNA (miRNA-205) and one anti-metastatic miRNA (miRNA-182), both of which showed an outstanding effect in synergistically abrogating tumours. The hydrogel would be dissociated by endogenous Dicer enzyme to release loaded therapeutic molecules, and in the meantime induce decomposition of tumor endogenous H2O2 to relieve tumor hypoxia. As a result, a remarkable synergistic therapeutic effect is achieved through the combined chemo-photodynamic therapy, which simultaneously triggers a series of anti-tumor immune responses. Besides, the hydrogel as the carrier which modified aptamer to targeted MDA-MB-231 has the advantages of good biocompatibility and low cytotoxicity. This strategy could be implemented to design any other microRNA (miRNA) as the carrier, combined with other treatment methods to treat human cancer, thereby overcoming the limitations of current cancer therapies.
研究领域:
癌症生物学
·
纳米技术
·
治疗学
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药学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2025
·Vol. 15
·期 29
·23966
·
IF 4.6
Yi Liu,Zheng Zhang,Huyang Du,Xiangjun Chen,Nan Hu,Tingting Yu,Meili Hou,Xiaolin Yu
Chemoresistance poses a critical challenge in cancer therapy across diverse tumor types, including non-small cell lung cancer (NSCLC), where chemotherapy-induced neuroendocrine differentiation (NED) of tumor cells plays a pivotal role in acquiring treatment resistance. This process significantly reduces chemotherapy efficacy, accelerates tumor progression, and ultimately worsens patient survival outcomes. The complex mechanisms underlying chemoresistance involve multiple factors, including enhanced DNA repair pathways, increased drug efflux capacity, and alterations in gene expression. Additionally, the tumor microenvironment, a dynamic ecosystem surrounding cancer cells, fosters a protective niche that exacerbates chemotherapy resistance. To address this challenge, we propose an innovative nanocomposite hydrogel system for the co-delivery of cisplatin and short hairpin RNA (shRNA) targeting protein arginine methyltransferase 5 (PRMT5), a key gene implicated in drug resistance. This system utilizes polyethyleneimine-modified mesoporous silica nanoparticles, which serve as nanocarriers, encapsulating cisplatin within the mesopores and coating the surface with methacryloylated hyaluronic acid (HA-MA). The design enables tumor microenvironment-responsive drug release, triggered by hyaluronidase enzymes abundant within the tumor, resulting in nanoparticle disassembly and the release of cisplatin. Simultaneously, the delivery of shRNA silences PRMT5 expression, enhancing chemosensitivity. By integrating targeted gene therapy with chemotherapy, this system offers a promising strategy for overcoming chemoresistance in NSCLC. Targeting both cancer cells and their microenvironment, this approach holds potential to transform the treatment of chemotherapy-resistant cancers, advancing more effective and personalized oncological therapies. An enzyme-responsive hydrogel to co-deliver cisplatin and shRNA, targeting NED-driven chemoresistance in NSCLC.
研究领域:
肿瘤学
·
纳米医学
·
药物递送
·
分子生物学
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癌症治疗
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）