Multi-responsive mesoporous polydopamine composite nanorods cooperate with nano-enzyme and photosensitiser for intensive immunotherapy of bladder cancer

Immunology. 2022 Oct;167(2):247-262. doi: 10.1111/imm.13534. Epub 2022 Jul 20.

Abstract

Bladder cancer is a common malignancy in the urinary system. Defects of drug molecules in bladder during treatment, such as passive diffusion, rapid clearance of periodic urination, poor adhesion and permeation abilities, lead to low delivery efficiency of conventional drugs and high recurrence rate of disease. In this study, we designed multi-responsive mesoporous polydopamine (PDA) composite nanorods cooperating with nano-enzyme and photosensitiser for intensive immunotherapy of bladder cancer. The strongly adhesive mesoporous PDA with wheat germ agglutinin on nanoparticles could specifically adhere to epithelial glycocalyx and made the nanoparticles aggregate in urinary pathways. Meanwhile, 2,3-dimethylmaleic anhydride could be hydrolysed in acidic conditions of tumour microenvironment, giving it a positive charge (charge reversal), which is more amenable to enter cancer cells. Afterwards, manganese dioxide nanorods could catalyse the reaction of excess H2 O2 in tumour microenvironment to generate active oxygen, so as to change the hypoxic environment in tumour, and achieve a pH-responsive for slow release of PD-L1. After the ICG was irradiated by infrared light, a large amount of singlet oxygen was generated, thereby enhancing the therapeutic effect and reducing toxicity in vivo. Besides, mesoporous PDA with indocyanine green photothermal agent could have a local heat up quickly under the near-infrared light to kill cancer cells, thereby enhancing therapeutic efficacy. Accordingly, this mesoporous PDA composite nanorods shed a light on bladder tumour treatment.

Keywords: adhesion property; composite nanorods; immunotherapy; nano-enzyme; photothermal agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen
  • Cell Line, Tumor
  • Doxorubicin
  • Humans
  • Immunotherapy
  • Indocyanine Green / metabolism
  • Indoles
  • Nanoparticles* / therapeutic use
  • Nanotubes*
  • Photosensitizing Agents
  • Polymers
  • Reactive Oxygen Species
  • Singlet Oxygen
  • Tumor Microenvironment
  • Urinary Bladder Neoplasms* / therapy
  • Wheat Germ Agglutinins

Substances

  • B7-H1 Antigen
  • Indoles
  • Photosensitizing Agents
  • Polymers
  • Reactive Oxygen Species
  • Wheat Germ Agglutinins
  • polydopamine
  • Singlet Oxygen
  • Doxorubicin
  • Indocyanine Green