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Updated: May 10, 2026
Evaluation of Polymeric Gene Delivery Nanoparticles by Nanoparticle Tracking Analysis and High-throughput Flow Cytometry
Published on: March 1, 2013
Trends in polymeric delivery of nucleic acids to tumors
Afrouz Yousefi1, Gert Storm, Raymond Schiffelers
1Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Abstract:
Delivery of nucleic acids to tumors has received extensive attention in the past few decades since these molecules are capable of treating disease by modulating the source of abnormalities. Although high efficiency and low toxicity of numerous delivery systems for nucleic acids have been approved frequently with in vitro assays, contradictions have been observed in many cases between these results and what has occurred in the dynamic in vivo situation. Filling this gap seems to be crucial for further preclinical development of such systems. In this paper, we discuss various barriers which polymeric DNA or siRNA nanoparticles encounter upon systemic administration with an aim to assist in designing more relevant in vitro assays. Furthermore, individual considerations concerning delivery of DNA and siRNA have been addressed.
Insights
Polymeric nanoparticles effectively deliver nucleic acids to tumors, but in vitro results often differ from in vivo outcomes. This study identifies barriers to systemic administration for improved preclinical development.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Gene Therapy
Background:
- Nucleic acid delivery to tumors is critical for disease treatment.
- In vitro studies often show high efficiency and low toxicity for delivery systems.
- A significant gap exists between in vitro findings and in vivo performance.
Purpose of the Study:
- To identify barriers encountered by polymeric DNA or siRNA nanoparticles during systemic administration.
- To guide the design of more predictive in vitro assays for nucleic acid delivery systems.
- To address specific considerations for DNA and siRNA delivery.
Main Methods:
- Review of existing literature on polymeric nanoparticle delivery systems.
- Analysis of challenges in systemic administration of nucleic acids.
- Discussion of in vitro versus in vivo discrepancies.
Main Results:
- Polymeric nanoparticles face multiple barriers upon systemic administration.
- In vitro assays do not fully recapitulate the complex in vivo environment.
- Specific challenges exist for both DNA and siRNA delivery.
Conclusions:
- Understanding in vivo barriers is essential for advancing preclinical nucleic acid delivery research.
- More relevant in vitro assays are needed to bridge the gap between lab results and clinical outcomes.
- Targeted strategies are required to overcome systemic administration hurdles for gene therapy applications.
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