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Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
Active Targeting Significantly Outperforms Nanoparticle Size in Facilitating Tumor-Specific Uptake in Orthotopic
William M MacCuaig1,2, Benjamin L Fouts1, Molly W McNally3,4
1Stephenson Cancer Center, University of Oklahoma, Oklahoma City, Oklahoma 73104, United States.
Abstract:
Nanoparticles are widely studied as theranostic vehicles for cancer; however, clinical translation has been limited due to poor tumor specificity. Features that maximize tumor uptake remain controversial, particularly when using clinically relevant models. We report a systematic study that assesses two major features for the impact on tumor specificity, i.e., active vs passive targeting and nanoparticle size, to evaluate relative influences in vivo. Active targeting via the V7 peptide is superior to passive targeting for uptake by pancreatic tumors, irrespective of nanoparticle size, observed through in vivo imaging. Size has a secondary effect on uptake for actively targeted nanoparticles in which 26 nm nanoparticles outperform larger 45 and 73 nm nanoparticles. Nanoparticle size had no significant effect on uptake for passively targeted nanoparticles. Results highlight the superiority of active targeting over nanoparticle size for tumor uptake. These findings suggest a framework for optimizing similar nonaggregate nanoparticles for theranostic treatment of recalcitrant cancers.
Insights
Active targeting significantly improves nanoparticle uptake in pancreatic tumors compared to passive targeting, with smaller nanoparticles showing better results when actively targeted. This research offers a framework for developing effective cancer theranostic vehicles.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Nanoparticles are promising theranostic agents for cancer treatment.
- Clinical translation is hindered by insufficient tumor specificity and uptake.
- Optimizing nanoparticle features for enhanced tumor targeting remains a critical challenge.
Purpose of the Study:
- To systematically evaluate the impact of active versus passive targeting and nanoparticle size on tumor specificity in vivo.
- To compare the relative influence of these features on pancreatic tumor uptake.
- To provide a framework for designing optimized nanoparticles for cancer theranostics.
Main Methods:
- A systematic in vivo study comparing active targeting (V7 peptide) with passive targeting.
- Evaluation of nanoparticle uptake across different sizes (26 nm, 45 nm, 73 nm).
- In vivo imaging techniques to quantify nanoparticle accumulation in tumors.
Main Results:
- Active targeting via V7 peptide demonstrated superior pancreatic tumor uptake compared to passive targeting, regardless of nanoparticle size.
- For actively targeted nanoparticles, smaller size (26 nm) resulted in higher tumor uptake than larger sizes (45 nm, 73 nm).
- Nanoparticle size did not significantly affect tumor uptake in passively targeted nanoparticles.
Conclusions:
- Active targeting is a more critical factor than nanoparticle size for enhancing tumor uptake.
- The V7 peptide confers significant tumor specificity, outperforming passive targeting strategies.
- Findings support a design framework prioritizing active targeting for developing nonaggregate nanoparticles for recalcitrant cancer theranostics.
