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Validation of ZIP4 as a tumour-associated antigen for nanotargeting
Ruixue Xu1, Neus Martinez-Bosch2, Francisco Rivera-Hueto3
1Integrative Biomedical Materials and Nanomedicine Lab, Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, PRBB, Barcelona, Spain.
Abstract:
Pancreatic ductal adenocarcinoma remains a highly aggressive and untreatable cancer. There is a need to develop a new PDAC-associated antigen-targeting drug delivery system to tackle this disease. We validated choosing ZIP4 as a putative target in PDAC theranostics. We developed a nanosystem composed of a fluorescent polystyrene core coated with gold nanoparticles onto which a ZIP4-specific polyclonal antibody is attached. The polystyrene core's fluorescence properties allow the nanosystem tracking by intravital imaging. We also developed two ZIP4-expressing cell lines by stably transfecting HEK293 and RWP1 cells with a ZIP4-coding plasmid that simultaneously provides cells with puromycin resistance. We studied the cell internalisation of the as-synthesised nanoparticles and demonstrated that ZIP4-expressing HEK293 and ZIP4-expressing RWP1 cells tended to take up more ZIP4-targeting nanoparticles. Moreover, we observed that ZIP4-targeting nanoparticles accumulated more in ZIP4-expressing HEK293 and RWP1 tumours when injected intravenously in a subcutaneous xenograft and an orthotopic in vivo model, respectively. Furthermore, the administration of these nanoparticles did not induce any significant systemic toxicity as determined by histological analysis of all organs. Altogether, these results provide the first evidence of the feasibility of using a ZIP4-targeting nanosystem further to design efficient therapeutic and diagnostic tools for PDAC.
Insights
Researchers developed a novel nanosystem targeting ZIP4 for pancreatic cancer theranostics. This ZIP4-targeting system shows promise for improved diagnosis and treatment of pancreatic ductal adenocarcinoma.
Area of Science:
- Oncology
- Nanotechnology
- Biomedical Engineering
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with limited treatment options.
- There is a critical need for novel targeted drug delivery systems for PDAC theranostics.
- ZIP4 has been identified as a potential target antigen for PDAC therapy.
Purpose of the Study:
- To develop and validate a novel nanosystem targeting the PDAC-associated antigen ZIP4.
- To evaluate the efficacy of the ZIP4-targeting nanosystem in preclinical models of PDAC.
- To assess the safety and biodistribution of the developed nanosystem.
Main Methods:
- A nanosystem was engineered with a fluorescent core, gold nanoparticles, and a ZIP4-specific antibody.
- ZIP4-expressing cell lines (HEK293 and RWP1) were created for in vitro and in vivo studies.
- Nanoparticle uptake, tumor accumulation, and systemic toxicity were evaluated in xenograft and orthotopic PDAC models.
Main Results:
- ZIP4-targeting nanoparticles demonstrated enhanced cellular uptake in ZIP4-expressing cells.
- Significant accumulation of nanoparticles was observed in tumors of both subcutaneous and orthotopic PDAC models.
- Histological analysis confirmed no significant systemic toxicity associated with nanoparticle administration.
Conclusions:
- The developed ZIP4-targeting nanosystem is feasible for PDAC theranostics.
- This nanosystem shows potential for the development of advanced diagnostic and therapeutic tools for pancreatic cancer.
- Further research is warranted to translate this nanosystem into clinical applications for PDAC treatment.
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