Nanoparticle entry into cells; the cell biology weak link.

Area of Science:

• Biomedical Engineering
• Cell Biology
• Nanotechnology

Background:

• Nanoparticles (NP) are promising for therapeutic delivery of drugs, proteins, and nucleic acids.
• NP development involves chemists, bioengineers, and material scientists (Stage 1) and cell/tissue studies (Stage 2).
• Animal model testing follows in Stage 3.

Purpose of the Study:

• To review current understanding of nanoparticle uptake mechanisms into mammalian cells via endocytosis.
• To identify sub-standard research practices in Stage 2 NP-cell interactions.
• To highlight misconceptions and suggest engagement with cell biologists.

Main Methods:

• Literature review of nanoparticle uptake mechanisms.
• Analysis of endocytosis pathways (phagocytosis, caveolae, macropinocytosis).
• Critique of current research quality in nanoparticle-cell interactions.

Main Results:

• Stage 2 research on NP-cell interactions is often sub-standard compared to Stage 1 chemistry.
• Evidence suggests exaggerated roles for caveolae and macropinocytosis in NP uptake.
• Phagocytosis is likely under-appreciated as a key NP uptake mechanism.

Conclusions:

• Improvement in cell biology research quality is crucial for advancing NP therapeutics.
• Re-evaluation of NP uptake mechanisms is needed, focusing on under-appreciated pathways like phagocytosis.
• Interdisciplinary collaboration between NP scientists and cell biologists is essential.