ArticleACS nano2025
Role of Serum Stability and Lipoprotein Interactions in Lipid Structure-Tumor Accumulation Relationship.
Article in ACS nano, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Physicochemical and molecular determinants of lipid migration through multicellular assemblies.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
Lipid-based formulations (liposomes, micelles, lipid nanoparticles, emulsions, lipid prodrugs) are the most popular systems for tumor drug delivery. At the same time, there is limited knowledge of the factors controlling the lipid structure-tumor accumulation relationship (STAR). To address this question, we synthesized a compact library of lipids with the shared cyanine Cy3 headgroup but variable tail hydrophobicity and headgroup-tail linkers. A shared fluorophore enabled the straightforward comparison of pharmacokinetics, tumor accumulation, and interactions of lipids with serum and cells. The library was formulated into nanomicelles with DSPE-PEG2000 and screened for tumor accumulation after intravenous injection in the syngeneic 4T1 breast cancer mouse model. Cy3 lipids with ester linkers mostly displayed poor tissue and tumor accumulation, except Cy3-cholesterol. Cy3 lipids with amide linkers and indocarbocyanine derivatives of Cy3 (DiI) showed better tumor accumulation. Nonlipid molecules Cy3-COOH and Cy3-PEG5000 were rapidly cleared with minimal accumulation in tumors. Of all lipids, DiI-C18 and DiI-C22 showed superior accumulation in 4T1 breast, GL261, and CT-2A orthotopic glioma models. Subsequent investigation revealed that chemical and formulation instability negatively affect the lipid pharmacokinetics and tumor accumulation. Lipids with stable linkers and hydrophobic chains caused slow clearance and high tumor buildup. On the other hand, short-chain lipids showed increased interaction with low-density lipoprotein (LDL), with strong evidence indicating accelerated clearance by the liver LDL receptor. The uptake of short-chain lipids by tumor cells in vitro was inhibited by interaction with lipoproteins. Overall, serum stability and lipoprotein interaction emerged as important in vitro predictors of favorable pharmacokinetics and tumor accumulation. These findings provide a framework for designing effective lipid-based therapeutics and imaging agents.
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Registered trials
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