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Updated: Apr 21, 2026
Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform
Published on: February 25, 2021
Increased gene delivery efficiency and specificity of a lipid-based nanosystem incorporating a glycolipid
Mariana Magalhães1, Dina Farinha2, Maria Conceição Pedroso de Lima1
1Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal ; Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal.
Abstract:
Hepatocellular carcinoma (HCC) is the third most common cause of death related to cancer diseases worldwide. The current treatment options have many limitations and reduced success rates. In this regard, advances in gene therapy have shown promising results in novel therapeutic strategies. However, the success of gene therapy depends on the efficient and specific delivery of genetic material into target cells. In this regard, the main goal of this work was to develop a new lipid-based nanosystem formulation containing the lipid lactosyl-PE for specific and efficient gene delivery into HCC cells. The obtained results showed that incorporation of 15% of lactosyl-PE into liposomes induces a strong potentiation of lipoplex biological activity in HepG2 cells, not only in terms of transgene expression levels but also in terms of percentage of transfected cells. In the presence of galactose, which competes with lactosyl-PE for the binding to the asialoglycoprotein receptor (ASGP-R), a significant reduction in biological activity was observed, showing that the potentiation of transfection induced by the presence of lactosyl-PE could be due to its specific interaction with ASGP-R, which is overexpressed in HCC. In addition, it was found that the incorporation of lactosyl-PE in the nanosystems promotes an increase in their cell binding and uptake. Regarding the physicochemical properties of lipoplexes, the presence of lactosyl-PE resulted in a significant increase in DNA protection and in a substantial decrease in their mean diameter and zeta potential, conferring them suitable characteristics for in vivo application. Overall, the results obtained in this study suggest that the potentiation of the biological activity induced by the presence of lactosyl-PE is due to its specific binding to the ASGP-R, showing that this novel formulation could constitute a new gene delivery nanosystem for application in therapeutic strategies in HCC.
Insights
Researchers developed a novel lipid-based nanosystem for gene therapy in hepatocellular carcinoma (HCC). This formulation enhances gene delivery efficiency and specificity by targeting the asialoglycoprotein receptor (ASGP-R) overexpressed in HCC cells.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death globally.
- Current HCC treatments face limitations, driving the need for novel therapeutic strategies.
- Gene therapy offers promise but requires efficient and specific delivery systems.
Purpose of the Study:
- To develop a novel lipid-based nanosystem for targeted gene delivery in HCC.
- To incorporate lactosyl-PE into liposomes for enhanced gene delivery into HCC cells.
- To investigate the mechanism of action and physicochemical properties of the novel nanosystem.
Main Methods:
- Formulation of lipid-based nanosystems containing lactosyl-PE.
- Evaluation of transfection efficiency and transgene expression in HepG2 cells.
- Competition assays with galactose to confirm ASGP-R mediated targeting.
- Assessment of cell binding, uptake, and physicochemical properties (DNA protection, size, zeta potential).
Main Results:
- Incorporation of 15% lactosyl-PE significantly enhanced transgene expression and transfection rates in HepG2 cells.
- Galactose competition assays confirmed specific targeting via the asialoglycoprotein receptor (ASGP-R).
- Lactosyl-PE enhanced cell binding and uptake, improved DNA protection, and reduced nanosystem size and zeta potential.
- The modified lipoplexes exhibited suitable characteristics for in vivo applications.
Conclusions:
- The novel lactosyl-PE-containing nanosystem demonstrates potent and specific gene delivery for HCC therapy.
- Targeting the overexpressed ASGP-R on HCC cells is a viable strategy for enhanced gene therapy.
- This formulation represents a promising new nanocarrier for therapeutic applications in HCC.
