Nanopharmaceuticals and Their Applications in Bladder Cancer Therapy: a Mini Review

The primary treatment for high-grade non-muscle invasive bladder cancer (NMIBC) is based on surgery by transurethral resection of bladder tumor (TURBT), followed by intravesical immunotherapy with Bacillus Calmette-Guerin (BCG) to prevent recurrence and to reduce the tumor progression. However, BCG therapy shows several undesirable effects. The current treatment on NMIBC is doxorubicin (DOX), but with high toxicity. Our nanotechnology strategy was done through scaffolds for the NMIBC treatment: graphene oxide (GO) and a nanostructured lipid carrier (NLC). A GO hybrid for administration of DOX and small interfering RNA (siRNA) was developed. This hybrids administered in vivo against NMIBC in rats gave absence of lesions. NLC was prepared by using a mixture of two lipids stabilized by a surfactant and DOX by high homogenization pressure technique. In this case showed a 20% of the animals exhibited benign lesions (papillary hyperplasia), however, in the presence of siRNA reached 40% of rats with benignant lesions. These two scaffolds are potential new drugs for DOX for bladder cancer treatment without any cardiotoxicity problems.

高级别非肌层浸润性膀胱癌（high-grade non-muscle invasive bladder cancer, NMIBC）的一线治疗方案以经尿道膀胱肿瘤切除术（transurethral resection of bladder tumor, TURBT）为核心术式，术后辅以膀胱内卡介苗（Bacillus Calmette-Guerin, BCG）免疫疗法，以预防肿瘤复发并延缓疾病进展。然而，卡介苗疗法存在多种不良反应。当前临床用于非肌层浸润性膀胱癌的治疗药物为多柔比星（doxorubicin, DOX），但该药物毒副作用较强。本研究针对非肌层浸润性膀胱癌的治疗开发了两种纳米支架载体：氧化石墨烯（graphene oxide, GO）与纳米结构脂质载体（nanostructured lipid carrier, NLC）。本研究成功研发出一种可同时递送多柔比星与小干扰RNA（small interfering RNA, siRNA）的氧化石墨烯杂化递送载体，将该载体应用于大鼠非肌层浸润性膀胱癌模型的体内实验后，未观察到任何病变反应。纳米结构脂质载体（NLC）采用高压均质技术制备，以表面活性剂稳定的双脂质混合物作为载体骨架负载多柔比星，该载体的单独给药实验显示，20%的受试大鼠出现良性病变（乳头状增生）；而当该载体联合小干扰RNA使用时，出现良性病变的大鼠比例升至40%。上述两种纳米支架载体有望成为替代多柔比星的新型膀胱癌治疗制剂，且不会引发任何心脏毒性问题。