A Novel 3DNA® Nanocarrier effectively delivers payloads to pancreatic tumors
Grace A McCarthy1, Aditi Jain2, Roberto Di Niro1
1Department of Surgery, Oregon Health & Science University, 2730 S. Moody Ave, Portland, OR 97201, USA; Brenden-Colson Center for Pancreatic Care, Knight Cancer Institute, Oregon Health & Science University, 2730 S. Moody Ave, Portland, OR 97201, USA.
Introduction:
Standard-of-care systemic chemotherapies for pancreatic ductal adenocarcinoma (PDAC) currently have limited clinical benefits, in addition to causing adverse side effects in many patients. One factor known to contribute to the poor chemotherapy response is the poor drug diffusion into PDAC tumors. Novel treatment methods are therefore drastically needed to improve targeted delivery of treatments. Here, we evaluated the efficacy of the 3DNA® Nanocarrier (3DNA) platform to direct delivery of therapeutics to PDAC tumors in vivo.
Materials And Methods:
A panel of PDAC cell lines and a patient tissue microarray were screened for established tumor-specific proteins to identify targeting moieties for active targeting of the 3DNA. NRG mice with or without orthotopic MIA PaCa-2-luciferase PDAC tumors were treated intraperitoneally with 100 μl of fluorescently labeled 3DNA.
Results:
Folic acid and transferrin receptors were significantly elevated in PDAC compared to normal pancreas. Accordingly, both folic acid- and transferrin-conjugated 3DNA treatments significantly increased delivery of 3DNA specifically to tumors in comparison to unconjugated 3DNA treatment. In the absence of tumors, there was an increased clearance of both folic acid-conjugated 3DNA and unconjugated 3DNA, compared to the clearance rate in tumor-bearing mice. Lastly, delivery of siLuciferase by folic acid-conjugated 3DNA in an orthotopic model of luciferase-expressing PDAC showed significant and prolonged suppression of luciferase protein expression and activity.
Conclusion:
Our study progresses the 3DNA technology as a reliable and effective treatment delivery platform for targeted therapeutic approaches in PDAC.
Insights
This study shows the 3DNA nanocarrier effectively targets pancreatic ductal adenocarcinoma (PDAC) tumors. Conjugated 3DNA enhances drug delivery and suppresses tumor growth, offering a promising new treatment strategy for PDAC.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) treatments face challenges due to poor drug diffusion and limited efficacy.
- Novel strategies are essential for improving targeted therapeutic delivery in PDAC.
- The 3DNA nanocarrier platform is explored for enhanced drug delivery to PDAC tumors.
Purpose of the Study:
- To evaluate the efficacy of the 3DNA nanocarrier platform for targeted therapeutic delivery in pancreatic ductal adenocarcinoma (PDAC).
- To identify and utilize tumor-specific targeting moieties for active targeting of the 3DNA nanocarrier in PDAC.
Main Methods:
- Screening of PDAC cell lines and patient tissues for tumor-specific proteins to identify targeting ligands.
- Utilizing folic acid and transferrin receptors as targeting moieties for 3DNA conjugation.
- In vivo evaluation in NRG mice with orthotopic MIA PaCa-2-luciferase PDAC tumors, assessing 3DNA delivery and therapeutic efficacy.
Main Results:
- Folic acid and transferrin receptors were found to be significantly elevated in PDAC.
- Folic acid- and transferrin-conjugated 3DNA demonstrated significantly increased and specific delivery to PDAC tumors compared to unconjugated 3DNA.
- Targeted 3DNA delivery led to significant and prolonged suppression of luciferase expression in an orthotopic PDAC model.
Conclusions:
- The 3DNA nanocarrier platform shows significant potential for targeted therapeutic delivery in pancreatic ductal adenocarcinoma (PDAC).
- Targeted conjugation enhances 3DNA accumulation in PDAC tumors, improving treatment efficacy.
- This technology represents a promising advancement for developing novel therapeutic strategies against PDAC.
