Lumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer

Abstract

Bo Hu,1 Ying Yan,2 Fei Tong,1 Long Xu,1 Jia Zhu,1 Guangtao Xu,1 Ruilin Shen1 1Department of Oncopathology, Institute of Diabetes and Urological Disease, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, 2Department of Rehabilitation Medicine, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China Background: Lumbrokinase (LK) is an enzyme complex with antithrombotic, antioxidant, antitumor, and immunomodulatory effects. It has been extensively studied and used in clinical anti-tumor therapy. However, its half-life is short, its bioavailability is low, and its toxicity and side effects are great, which greatly limit its clinical application. Therefore, LK is often combined with other drugs (such as immune agents, hormones, or Chinese herbal medicine) to reduce its dosage and side effects and to improve its anti-tumor effects. Methods and results: Here, we described an LK/paclitaxel (PTX) nanocarrier based on poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyoxycarbonyl-l-lysine)-r-poly(l-lysine)) (PEG-b-(PELG-g-(PZLL-r-PLL))). In the present study, LK and PTX were loaded by electrostatic and/or hydrophobic effects under mild conditions, thereby increasing the half-life and bioavailability of the drugs via the sustained release and enhancement of tumor site enrichment by the LK/PTX/PEG-b-(PELG-g-(PZLL-r-PLL)) complex through passive targeting. In this study, using bladder cancer cells (J82 cells) and rat bladder cancer model as the object, the structure of the nanocarrier, the relationship between drugs composition and antitumor properties were systematically studied. Conclusion: We propose that the block copolymer PEG-b-(PELG-g-(PZLL-r-PLL)) may function as a potent nanocarrier for augmenting anti-bladder cancer pharmacotherapy, with unprecedented clinical benefits. Keywords: copolymer nanoparticles, lumbrokinase, paclitaxel, bladder cancer, microvessel density, p53, cyclin B1

Keywords

• copolymer nanoparticles
• lumbrokinase
• paclitaxel
• bladder cancer
• microvessel density
• p53
• cyclin B1