Cellular and Molecular Life Sciences

, Volume 66, Issue 17, pp 2873–2896 | Cite as

Nanocarriers’ entry into the cell: relevance to drug delivery

  • Hervé Hillaireau
  • Patrick CouvreurEmail author


Nanocarriers offer unique possibilities to overcome cellular barriers in order to improve the delivery of various drugs and drug candidates, including the promising therapeutic biomacromolecules (i.e., nucleic acids, proteins). There are various mechanisms of nanocarrier cell internalization that are dramatically influenced by nanoparticles’ physicochemical properties. Depending on the cellular uptake and intracellular trafficking, different pharmacological applications may be considered. This review will discuss these opportunities, starting with the phagocytosis pathway, which, being increasingly well characterized and understood, has allowed several successes in the treatment of certain cancers and infectious diseases. On the other hand, the non-phagocytic pathways encompass various complicated mechanisms, such as clathrin-mediated endocytosis, caveolae-mediated endocytosis and macropinocytosis, which are more challenging to control for pharmaceutical drug delivery applications. Nevertheless, various strategies are being actively investigated in order to tailor nanocarriers able to deliver anticancer agents, nucleic acids, proteins and peptides for therapeutic applications by these non-phagocytic routes.


Liposomes Nanoparticles Polymeric micelles Endocytosis Phagocytosis Clathrin Caveolae Macropinocytosis 



Blood-brain barrier


Clathrin-mediated endocytosis


Caveolae-mediated endocytosis


Folic acid


Human serum albumin


Intracellular cell adhesion molecule 1


Monoclonal antibody








Poly(lactic acid)


Poly(lactic-co-glycolic acid)




Reticuloendothelial system


Receptor-mediated endocytosis


Short-interfering RNA


Trans-activating transcriptional activator peptide




Transferrin receptor


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Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  1. 1.School of Engineering and Applied SciencesHarvard UniversityCambridgeUSA
  2. 2.Faculté de Pharmacie, UMR CNRS 8612Université Paris-Sud 11Châtenay MalabryFrance

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