Pre-instillation of tumor microparticles enhances intravesical chemotherapy of nonmuscle-invasive bladder cancer through a lysosomal pathway

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• 作者：Xun Jin^a ; ¹ ; Jingwei Ma^b ; ^c ; ¹ ; Xiaoyu Liang^a ; ¹ ; Ke Tang^b ; Yuying Liu^a ; Xiaonan Yin^a ; Yi Zhang^a ; Huafeng Zhang^a ; Pingwei Xu^b ; Degao Chen^a ; Tianzhen Zhang^a ; Jinzhi Lu^a ; Zhuowei Hu^d ; Xiaofeng Qin^e ; Xiaoyong Zeng^f ; Longcheng Li^g ; Bo Huang^a ; ^b ; ^{tjhuangbo@hotmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Bladder cancer cell ; Microparticles ; Lysosomes ; Chemosensitizer ; Recurrence
• 刊名：Biomaterials
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：113
• 期：Complete
• 页码：93-104
• 全文大小：3750 K

文摘

Nonmuscle-invasive bladder cancer (NMIBC) is treated with transurethral resection followed by intravesical chemotherapy. However, drug-resistant tumorigenic cells cannot be eliminated, leading to half of the treated cancers recur with increased stage and grade. Innovative approaches to enhance drug sensitivity and eradicate tumorigenic cells in NMIBC treatment are urgently needed. Here, we show that pre-instillation of tumor cell-derived microparticles (T-MP) as natural biomaterials markedly enhance the inhibitory effects of intravesical chemotherapy on growth and hematuria occurrence of orthotropic bladder cancer in mice. We provide evidence that T-MPs enter and increase the pH value of lysosomes from 4.6 to 5.6, leading to the migration of drug-loaded lysosomes along microtubule tracks toward the nucleus and discharging the drugs whereby for the entry of the nucleus. We propose that T-MPs may function as a potent sensitizer for augmenting NMIBC chemotherapy with unprecedented clinical benefits.