肿瘤细胞解离增强型膀胱癌膀胱内化疗

SmartMat Pub Date : 2024-01-22 DOI:10.1002/smm2.1276
Zhaoyu Ma, Zhiduo Sun, Zhichao Ye, Kai Cai, Wenbin Zhong, Weiguang Yuan, Weiyun Zhang, Jin Zhang, Kai Zhang, Huageng Liang, Heyou Han, Yanli Zhao
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引用次数: 0

摘要

频繁的膀胱内化疗仍是膀胱癌术后采用的临床方案,但存在粘附性低、选择性差、渗透性低和耐药性等问题。在此,我们开发了一种巧妙的膀胱癌解离方法,以加强膀胱内化疗和肿瘤与尿液的自我排异。在壳聚糖改性的空心金纳米棒中装入临床上常用的膀胱灌注药物多柔比星(Dox),并在其上包覆癌细胞膜。膀胱灌注后,该纳米平台在同源靶向作用下对膀胱肿瘤具有高亲和力,有助于长期保留。在近红外-II 激光照射下,光热效应加速了货物的卸载,释放出的乙二胺四乙酸通过剥夺和螯合细胞间钙依赖性连接蛋白中的 Ca2+,破坏瘤内连接。随之而来的瘤间解离使 Dox 能够深入渗透,并使脱落的小肿瘤随尿液排出体外。这种独特的肿瘤解离概念为现代临床膀胱内化疗带来了巨大的希望,或许也适用于其他胃肠道恶性肿瘤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Tumor cell dissociation‐enhanced intravesical chemotherapy of orthotopic bladder cancer
Frequent intravesical chemotherapy is still the adopted clinical option after bladder cancer surgery with low adhesion, poor selectivity, low permeability, and drug resistance. Herein, we develop an ingenious bladder cancer dissociation method to enhance intravesical chemotherapy and tumor self‐exclusion with urine. Ethylene diamine tetraacetic acid (EDTA), a common Ca2+ chelator, is loaded with the typical clinical bladder instillation drug doxorubicin (Dox) in chitosan‐modified hollow gold nanorods and subsequently coated with cancer cell membranes. After bladder perfusion, the nanoplatform exhibits high affinity toward bladder tumors under homologous targeting, assisting in long‐term retention. Under NIR‐II laser irradiation, the photothermal effect accelerates the unloading of cargo, and the released EDTA then disrupts intratumoral junctions by depriving and chelating Ca2+ from the intercellular calcium‐dependent connexin. The consequential intertumoral dissociation gives access to the deeper penetration of Dox and allows the exclusion of the shed small tumor masses from the body with the urine. This distinctive tumor dissociation concept holds great promise for modern clinical intravesical chemotherapy and perhaps for other gastrointestinal malignancies.
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