1. Academic Validation
  2. R11 modified tumor cell membrane nanovesicle-camouflaged nanoparticles with enhanced targeting and mucus-penetrating efficiency for intravesical chemotherapy for bladder cancer

R11 modified tumor cell membrane nanovesicle-camouflaged nanoparticles with enhanced targeting and mucus-penetrating efficiency for intravesical chemotherapy for bladder cancer

  • J Control Release. 2022 Oct 10;351:834-846. doi: 10.1016/j.jconrel.2022.09.055.
Bin Zheng 1 Zhenghong Liu 1 Heng Wang 1 Li Sun 1 Wing-Fu Lai 2 Haibao Zhang 3 Jinxue Wang 4 Yang Liu 5 Xiaowen Qin 1 Xiaolong Qi 1 Shuai Wang 1 Youqing Shen 6 Pu Zhang 7 Dahong Zhang 8
Affiliations

Affiliations

  • 1 Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.
  • 2 Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, HongKong, China.
  • 3 Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi An Shanxi 710049, China.
  • 4 Rehabilitation Medcine Center, Department of Neuroelectrophysiology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.
  • 5 Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.
  • 6 Center for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310014, China. Electronic address: [email protected].
  • 7 Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China. Electronic address: [email protected].
  • 8 Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China. Electronic address: [email protected].
Abstract

Intravesical chemotherapy is generally used in the clinic for treating bladder Cancer (BCa), but its efficacy is limited due to the permeation barrier and side effects caused by the off-targeting of normal urothelial cells. In this study, BCa cell-derived membrane nanovesicles were used as drug carriers, and their homologous tumor-targeting capacity was utilized. A BCa-targeting hendeca-arginine peptide was functionalized onto the nanovesicles to impart a mucus-penetrating ability and thus overcome the permeation barrier. The tumor-targeting and mucus-penetrating nanovesicles were stable in urine, were highly permeable to the glycosaminoglycan layer, and specifically targeted BCa. The vesicles were internalized through caveolin-mediated endocytosis, were transported to nonlysosome-localized intracellular regions, and efficiently infiltrated bladder tumor spheroids. In in vivo intravesical chemotherapy, the nanovesicles achieved chemo-resection in murine orthotopic BCa models. This BCa-targeting and mucus-penetrating drug delivery system may be promising for the intravesical chemotherapy of BCa.

Keywords

Bladder cancer; Cell membrane-camouflaged nanoparticle; Intravesical therapy; Mucus-penetrating.

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