Department of Urology, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen, 518000, China.
Shenzhen Following Precision Medical Research Institute, Shenzhen, 518000, China.
Small. 2019 Jun;15(25):e1900936. doi: 10.1002/smll.201900936. Epub 2019 May 10.
Surgical intervention combined with intravesical instillation of chemotherapeutics to clear residual cancer cells after operation is the current standard treatment method for bladder cancer. However, the poor bioavailability of active pharmaceutical ingredients for bladder cancer cells on account of the biological barriers of bladder mucosa, together with significant side effects of currently used intravesical medicine, have limited the clinical outcomes of localized adjuvant therapy for bladder cancer. Aiming at improved intravesical instillation therapy of bladder cancer, a fluorinated polyethylenimine (F-PEI) is employed here for the transmucosal delivery of an active venom peptide, polybia-mastoparan I (MPI), which shows selective antiproliferative effect against various bladder cancer cell lines. Upon simple mixing, MPI and F-PET would coassemble to form stable nanoparticles, which show greatly improved cross-membrane and transmucosal penetration capacities compared with MPI alone or nonfluorinated MPI/PEI nanoparticles. MPI/F-PEI shows higher in vivo tumor growth inhibition efficacy for local treatment of a subcutaneous tumor model. More excitingly, as further demonstrated in an orthotopic bladder cancer model, MPI/F-PEI offers remarkably improved therapeutic effects compared to those achieved by free MPI or the first-line bladder cancer drug mitomycin C. This work presents a new transmucosal delivery carrier particularly promising for intravesical instillation therapy of bladder cancer.
手术干预联合膀胱内化疗药物灌注以清除术后残留癌细胞是目前膀胱癌的标准治疗方法。然而，由于膀胱黏膜的生物学屏障，膀胱癌细胞的活性药物成分生物利用度差，再加上目前使用的膀胱内药物的显著副作用，限制了膀胱癌局部辅助治疗的临床效果。为了改善膀胱癌的膀胱内灌注治疗，本研究采用氟化聚乙烯亚胺（F-PEI）作为活性毒液肽多形木叶蠊抗菌肽 I（MPI）的跨黏膜传递载体，其对多种膀胱癌细胞系具有选择性的抗增殖作用。MPI 和 F-PET 简单混合后会共组装形成稳定的纳米颗粒，与单独的 MPI 或未氟化的 MPI/PEI 纳米颗粒相比，其跨膜和跨黏膜渗透能力大大提高。MPI/F-PEI 对皮下肿瘤模型的局部治疗显示出更高的体内肿瘤生长抑制效果。更令人兴奋的是，正如在原位膀胱癌模型中进一步证明的那样，与游离 MPI 或一线膀胱癌药物丝裂霉素 C 相比，MPI/F-PEI 提供了显著改善的治疗效果。这项工作提出了一种新的跨黏膜传递载体，特别有希望用于膀胱癌的膀胱内灌注治疗。
