基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Localized Cancer Treatment Using Thiol-Ene Hydrogels for Dual Drug Delivery.
Localized Cancer Treatment Using Thiol-Ene Hydrogels for Dual Drug Delivery.
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可注射水凝胶有望用于联合癌症治疗中的局部、可控药物递送。本研究构建了一种硫醇-烯偶联水凝胶,通过交联巯基修饰透明质酸(HASH)和乙烯砜修饰β-环糊精(CDVS)形成。通过改变HASH分子量(23或99 kDa)及CDVS修饰度(16%或33%),合成四种配方(23Gel-16、23Gel-33、99Gel-16和99Gel-33)。流变学分析证实,黏弹性随分子量和修饰度增加而增强,顺序为99Gel-33>99Gel-16>23Gel-33>23Gel-16。该系统可联合递送多柔比星(DOX)和香芹酚(CRV),并具有肿瘤响应性降解和可调控释放特性。在模拟肿瘤条件下,DOX释放加快(46小时释放100%,而在PBS中为58.7%);CRV则先快速释放,随后持续释放。水凝胶促进间充质干细胞增殖,并有效抑制三阴性乳腺癌细胞。该可注射、肿瘤响应型水凝胶有望成为微创、个体化癌症治疗平台。
Combinatorial cancer therapy benefits from injectable hydrogels for localized, controlled drug delivery.
This study presents a thiol-ene conjugated hydrogel formed by cross-linking thiol-modified hyaluronic acid (HASH) with vinyl sulfone-modified -cyclodextrin (CDVS). Four formulations (23Gel-16, 23Gel-33, 99Gel-16, 99Gel-33) were synthesized by varying HASH molecular weight (23 or 99 kDa) and CDVS modification (16% or 33%). Rheological analysis confirmed enhanced viscoelasticity with increasing molecular weight and modification (99Gel-33 > 99Gel-16 > 23Gel-33 > 23Gel-16).
The system enabled combinatorial delivery of doxorubicin (DOX) and carvacrol (CRV), exhibiting tumor-responsive degradation and tunable release. DOX release accelerated under tumor-mimicking conditions (100% in 46 h vs 58. 7% in PBS), while CRV showed an initial burst followed by sustained release. The hydrogel promoted mesenchymal stem cell proliferation and effectively inhibited triple-negative breast cancer cells. This injectable, tumor-responsive hydrogel system offers a promising platform for minimally invasive, personalized cancer therapy.
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