2. Academic Validation
  3. IGF1 receptor-targeted black TiO2 nanoprobes for MRI-guided synergetic photothermal-chemotherapy in drug resistant pancreatic tumor

IGF1 receptor-targeted black TiO2 nanoprobes for MRI-guided synergetic photothermal-chemotherapy in drug resistant pancreatic tumor

  • J Nanobiotechnology. 2022 Jul 6;20(1):315. doi: 10.1186/s12951-022-01525-3.
Kaiwei Xu  # 1,  Lufei Jin  # 1,  Liu Xu  # 1,  Yuchao Zhu 1,  Lu Hong 1,  Chunshu Pan 2,  Yanying Li 2 3,  Junlie Yao 2 3,  Ruifen Zou 2 3,  Weiwei Tang 1,  Jianhua Wang 4,  Aiguo Wu 5 6,  Wenzhi Ren 7 8 9
Affiliations

Affiliations

  • 1 Department of Radiology, the Affiliated Hospital of Medical School, Ningbo University, 247 Renmin Road, Jiangbei District, Ningbo, 315020, Zhejiang, China.
  • 2 Cixi Institute of Biomedical Engineering, International Cooperation Base of Biomedical Materials Technology and Application, Chinese Academy of Science (CAS) Key Laboratory of Magnetic Materials and Devices & Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, CAS, 1219 ZhongGuan West Road, Ningbo, 315201, China.
  • 3 Advanced Energy Science and Technology Guangdong Laboratory, Huizhou, 516000, China.
  • 4 Department of Radiology, the Affiliated Hospital of Medical School, Ningbo University, 247 Renmin Road, Jiangbei District, Ningbo, 315020, Zhejiang, China. wangjianhua@nbu.edu.cn.
  • 5 Cixi Institute of Biomedical Engineering, International Cooperation Base of Biomedical Materials Technology and Application, Chinese Academy of Science (CAS) Key Laboratory of Magnetic Materials and Devices & Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, CAS, 1219 ZhongGuan West Road, Ningbo, 315201, China. aiguo@nimte.ac.cn.
  • 6 Advanced Energy Science and Technology Guangdong Laboratory, Huizhou, 516000, China. aiguo@nimte.ac.cn.
  • 7 Cixi Institute of Biomedical Engineering, International Cooperation Base of Biomedical Materials Technology and Application, Chinese Academy of Science (CAS) Key Laboratory of Magnetic Materials and Devices & Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, CAS, 1219 ZhongGuan West Road, Ningbo, 315201, China. renwzh@nimte.ac.cn.
  • 8 Advanced Energy Science and Technology Guangdong Laboratory, Huizhou, 516000, China. renwzh@nimte.ac.cn.
  • 9 Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, 315016, China. renwzh@nimte.ac.cn.
  • # Contributed equally.
PMID: 35794573 DOI: 10.1186/s12951-022-01525-3
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest malignant tumors with features of matrix barrier caused poor drug permeability, and susceptibility to drug resistance. Herein, a PDAC and its stromal cell dual-targeted photothermal-chemotherapy strategy is explored to loosen the matrix and reverse drug resistance. To achieve this goal, black TiO2-Gd nanocomposites were conjugated with Insulin like growth factor 1 (IGF1), and loaded with gemcitabine (GEM) to construct bTiO2-Gd-IGF1-GEM nanoprobes. In vitro results show that under 808 nm near-infrared irradiation, killing effect of the nanoprobes on drug-resistant MIA PaCa-2 cell is 3.3 times than that of GEM alone. In vivo experiments indicate the synergetic photothermal-chemotherapy not only loosens fibrous matrix of pancreatic tumor model, but also dramatically inhibits tumor growth, and almost completely eradicates the tumor after 12 days of treatment. In addition, relaxation rate of the nanoprobes is 8.2 times than commercial contrast agent Magnevist, therefore boosts the signal of magnetic resonance imaging in pancreatic tumor. In conclusion, our results reinforce that the prepared nanoprobes are promising to break matrix barrier and overcome drug resistance in PDAC.

Keywords

Black TiO2 nanoparticles; Drug resistance; Pancreatic tumor; Targeted photothermal therapy.

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