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Nanocarriers’ entry into the cell: relevance to drug delivery

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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.

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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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Hillaireau, H., Couvreur, P. Nanocarriers’ entry into the cell: relevance to drug delivery. Cell. Mol. Life Sci. 66, 2873–2896 (2009). https://doi.org/10.1007/s00018-009-0053-z

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