ArticleJournal of controlled release : official journal of the Controlled Release Society2019
Tailoring the lipid composition of nanoparticles modulates their cellular uptake and affects the viability of triple negative breast cancer cells.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 101 citations in OpenAlex.
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- Machine learning-driven exosome-mimetic lipid nanoparticles for tumor-specific targeting.Nano convergence · 2026Article
- Liposome-mediated gene delivery: A comprehensive review of biophysical parameters, lipid composition and targeting strategies.ADMET & DMPK · 2026Review
- Lipid Nanoparticle-Mediated Antifungal and Immunomodulatory Therapy for Neuromycoses.International journal of nanomedicine · 2026Review
- Antiviral Activity of Liposomes Containing Natural Compounds Against CHIKV.Pharmaceutics · 2025Article
- Eliciting antitumor immunity via therapeutic cancer vaccines.Cellular & molecular immunology · 2025Review
- Nanoparticles for Cancer Immunotherapy: Innovations and Challenges.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Gold Nanoparticle Adsorption and Uptake are Directed by Particle Capping Agent.Small science · 2025Article
- The role of excipients in lipid nanoparticle metabolism: implications for enhanced therapeutic effect.Therapeutic delivery · 2025Review
- Optimized and Functionalized Carvacrol-Loaded Nanostructured Lipid Carriers for Enhanced Cytotoxicity in Breast Cancer Cells.Pharmaceutics · 2025Article
- Advances in Targeted Engineered Nanoparticle-Based Therapeutics for Respiratory Diseases: Current Insights and Future Perspectives.International journal of nanomedicine · 2025Review
- Cell Membrane Fatty Acids and PIPs Modulate the Etiology of Pancreatic Cancer by Regulating AKT.Nutrients · 2024Article
- Exploring the landscape of Lipid Nanoparticles (LNPs): A comprehensive review of LNPs types and biological sources of lipids.International journal of pharmaceutics: X · 2024Review
- Optimized microfluidic formulation and organic excipients for improved lipid nanoparticle mediated genome editing.Lab on a chip · 2024Article
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- Computational biology and artificial intelligence in mRNA vaccine design for cancer immunotherapy.Frontiers in cellular and infection microbiology · 2024Review
- Liposomal Nano-Based Drug Delivery Systems for Breast Cancer Therapy: Recent Advances and Progresses.Anti-cancer agents in medicinal chemistry · 2024Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Lipid nanoparticles are used widely as anticancer drug and gene delivery systems. Internalizing into the target cell is a prerequisite for the proper activity of many nanoparticulate drugs. We show here, that the lipid composition of a nanoparticle affects its ability to internalize into triple-negative breast cancer cells. The lipid headgroup had the greatest effect on enhancing cellular uptake compared to other segments of the molecule. Having a receptor-targeted headgroup induced the greatest increase in cellular uptake, followed by cationic amine headgroups, both being superior to neutral (zwitterion) phosphatidylcholine or to negatively-charged headgroups. The lipid tails also affected the magnitude of cellular uptake. Longer acyl chains facilitated greater liposomal cellular uptake compared to shorter tails, 18:0 > 16:0 > 14:0. When having the same lipid tail length, unsaturated lipids were superior to saturated ones, 18:1 > 18:0. Interestingly, liposomes composed of phospholipids having 14:0 or 12:0-carbon-long-tails, such as DMPC and DLPC, decreased cell viability in a concertation dependent manner, due to a destabilizing effect these lipids had on the cancer cell membrane. Contrarily, liposomes composed of phospholipids having longer carbon tails (16:0 and 18:0), such as DPPC and HSPC, enhanced cancer cell proliferation. This effect is attributed to the integration of the exogenous liposomal lipids into the cancer-cell membrane, supporting the proliferation process. Cholesterol is a common lipid additive in nanoscale formulations, rigidifying the membrane and stabilizing its structure. Liposomes composed of DMPC (14:0) showed increased cellular uptake when enriched with cholesterol, both by endocytosis and by fusion. Contrarily, the effect of cholesterol on HSPC (18:0) liposomal uptake was minimal. Furthermore, the concentration of nanoparticles in solution affected their cellular uptake. The higher the concentration of nanoparticles the greater the absolute number of nanoparticles taken up per cell. However, the efficiency of nanoparticle uptake, i.e. the percent of nanoparticles taken up by cells, decreased as the concentration of nanoparticles increased. This study demonstrates that tuning the lipid composition and concentration of nanoscale drug delivery systems can be leveraged to modulate their cellular uptake.
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