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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 Couvreur
Review

Abstract

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.

Keywords

Liposomes Nanoparticles Polymeric micelles Endocytosis Phagocytosis Clathrin Caveolae Macropinocytosis 

Abbreviations

BBB

Blood-brain barrier

CME

Clathrin-mediated endocytosis

CvME

Caveolae-mediated endocytosis

FA

Folic acid

HSA

Human serum albumin

ICAM-1

Intracellular cell adhesion molecule 1

MAb

Monoclonal antibody

ODN

Oligonucleotide

PACA

Poly(alkylcyanoacrylate)

PEG

Poly(ethyleneglycol)

PLA

Poly(lactic acid)

PLGA

Poly(lactic-co-glycolic acid)

PSt

Polystyrene

RES

Reticuloendothelial system

RME

Receptor-mediated endocytosis

siRNA

Short-interfering RNA

TAT

Trans-activating transcriptional activator peptide

Tf

Transferrin

TfR

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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