A Urinary Drug-Disposing Approach as an Alternative to Intravesical Chemotherapy for Treating Nonmuscle Invasive Bladder Cancer.
A Urinary Drug-Disposing Approach as an Alternative to Intravesical Chemotherapy for Treating Nonmuscle Invasive Bladder Cancer.
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DOI：
10.1158/0008-5472.can-21-2897
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发表时间：
2022-04-01
期刊：
影响因子：
11.2
通讯作者：
Law B
中科院分区：
文献类型：
--
作者：
Bellat V;Michel AO;Thomas C;Stokol T;Choi BB;Law B
一种无创的药物输送方法，其针对尿液系统，以克服当前面临有效治疗膀胱癌的屏障。
非肌肉浸润性膀胱癌（NMIBC）的标准治疗是肿瘤的尿道切除术，其次是静脉治疗（IT），其中包括对芽孢杆菌的溶液直接灌输芽孢杆菌疫苗或化学疗法的溶液这种疾病的速度仍然不可接受。导管插入过程是侵入性的，痛苦的，并且具有增加的感染风险，导致患者的生活质量和依从性不足。通过肾脏清理，当将治疗用于NMIBC时，这种“缺点”可以是有利的。改善NMIBC处理的方法。携带人类膀胱肿瘤的小鼠与该肿瘤不同（静脉注射）。临床上使用了这种UDD方法来治疗肾脏肿瘤，并提供其他药物（例如阿霉素）。尿液系统。
一种无创的药物输送方法，其针对尿液系统，以克服当前面临有效治疗膀胱癌的屏障。
A noninvasive drug delivery approach that targets the urinary system overcomes the current barriers facing effective treatment of bladder cancer. The standard treatment of nonmuscle invasive bladder cancer (NMIBC) is transurethral resection of the tumors, followed by intravesical therapy (IT), which comprises a direct instillation of a solution of Bacillus Calmette-Guérin vaccine or chemotherapy into the bladder. However, the recurrence rate in this disease remains unacceptably high. IT is a local treatment that fails to reach tumors developed in the upper urinary tract (ureter and renal pelvis). The catheterization procedure required for IT is invasive, painful, and poses an increased infection risk, resulting in poor patient quality of life and compliance. There is an unmet need for a potent, comprehensive, and noninvasive option. Without chemical modifications, peptides are rapidly removed by renal clearance. This “shortcoming” can be advantageous when used as a drug carrier for directing therapy to NMIBC. Here we develop a urinary drug-disposing (UDD) approach to improve NMIBC treatment. A 12-amino acid bio-inert peptide (Bdd) that can be exclusively eliminated via renal filtration was generated for delivering the microtubule inhibitor DM1 to NMIBC with minimal nonspecific accumulation in other organs. The UDD approach prolonged survival of mice bearing human bladder tumors. Unlike IT, the treatment was given noninvasively (intravenously). Furthermore, it was more effective at suppressing tumor growth than clinically used IT (mitomycin) and safer than free DM1. The application of this UDD approach to treat kidney tumors and deliver other drugs such as doxorubicin was also demonstrated. Overall, the rapid renal clearance of peptides can be exploited to direct cancer therapies to the urinary system. A noninvasive drug delivery approach that targets the urinary system overcomes the current barriers facing effective treatment of bladder cancer.
影响因子：
6.2
作者：
Bellat V;Lee HH;Vahdat L;Law B
通讯作者：
Law B