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Review
. 2013 Nov 1;5(11):a016980.
doi: 10.1101/cshperspect.a016980.

Exploiting endocytosis for nanomedicines

Affiliations
Review

Exploiting endocytosis for nanomedicines

Akin Akinc et al. Cold Spring Harb Perspect Biol. .

Abstract

In this article, we briefly review the endocytic pathways used by cells, pointing out their defining characteristics and highlighting physical limitations that may direct the internalization of nanoparticles to a subset of these pathways. A more detailed description of these pathways is presented in the literature. We then focus on the endocytosis of nanomedicines and present how various nanomaterial parameters impact these endocytic processes. This topic is an area of active research, motivated by the recognition that an improved understanding of how nanomaterials interact at the molecular, cellular, and whole-organism level will lead to the design of better nanomedicines in the future. Next, we briefly review some of the important nanomedicines already on the market or in clinical development that serve to exemplify how endocytosis can be exploited for medical benefit. Finally, we present some key unanswered questions and remaining challenges to be addressed by the field.

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Figures

Figure 1.
Figure 1.
Mechanisms of endocytosis and their relationship with size of either endogenous or exogenous cargo.
Figure 2.
Figure 2.
(A) A two-dimensional (2D) phase diagram on the nanoparticle radius ligand density plane characterizes the interrelated effects of particle size and ligand density on the cellular uptake. (From Yuan et al. 2010; adapted, with permission, from the American Physical Society © 2010.) (B) Coarse-grained simulations of curvature-inducing proteins bound on membranes at different times show that a membrane-bound protein cluster drives the formation of vesicles whose size is controlled by the local curvature uptake. (From Reynwar et al. 2007; adapted, with permission, from the Nature Publishing Group © 2010.) (C) Endocytosis efficiency as a function of the polymersome diameter for different patchy cell-active (gold) and cell-inert (blue) nanoparticles.
Figure 3.
Figure 3.
Mechanism of viral and artificial system endosomal escape.
Figure 4.
Figure 4.
General structure of antibody drug conjugates (ADC) and targeted prodrugs.

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