Insight into nanoparticle cellular uptake and intracellular targeting - PubMed (original) (raw)

Review

Insight into nanoparticle cellular uptake and intracellular targeting

Basit Yameen et al. J Control Release. 2014.

Abstract

Collaborative efforts from the fields of biology, materials science, and engineering are leading to exciting progress in the development of nanomedicines. Since the targets of many therapeutic agents are localized in subcellular compartments, modulation of nanoparticle-cell interactions for efficient cellular uptake through the plasma membrane and the development of nanomedicines for precise delivery to subcellular compartments remain formidable challenges. Cellular internalization routes determine the post-internalization fate and intracellular localization of nanoparticles. This review highlights the cellular uptake routes most relevant to the field of non-targeted nanomedicine and presents an account of ligand-targeted nanoparticles for receptor-mediated cellular internalization as a strategy for modulating the cellular uptake of nanoparticles. Ligand-targeted nanoparticles have been the main impetus behind the progress of nanomedicines towards the clinic. This strategy has already resulted in remarkable progress towards effective oral delivery of nanomedicines that can overcome the intestinal epithelial barrier. A detailed overview of the recent developments in subcellular targeting as a novel platform for next-generation organelle-specific nanomedicines is also provided. Each section of the review includes prospects, potential, and concrete expectations from the field of targeted nanomedicines and strategies to meet those expectations.

Keywords: Intracellular distribution; Nanomedicine; Nanoparticle cellular uptake; Non-targeted and targeted nanoparticles; Subcellular targeting.

Copyright © 2014 Elsevier B.V. All rights reserved.

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Conflict of interest statement

The rest of the authors declare no conflict of interest.

Figures

Fig. 1

Fig. 1

Illustration of internalization pathways discussed in this article (phagocytosis, macropinocytosis, clathrin-dependent endocytosis, clathrin-independent endocytosis, and caveolin-dependent endocytosis). The fate of internalized cargo and localization to subcellular compartments are also depicted. ER: endoplasmic reticulum, NLS: nuclear localization signal, NPC: nuclear pore complex, TPP: triphenylphosphonium cation. Adapted and reproduced with permission from [90,92].

Fig. 2

Fig. 2

(A) Schematic illustration of PSMA targeted BIND-014 docetaxel loaded polymeric nanoparticles. (B) Depiction of achievable nanomedicine attribtutes, red line represents the optimized properties. (C) CT scan evidencing a remarkable regression of lung metastases in 51 year male patient treated with two cycles of BIND-014. Reproduced with permission from [18].

Fig. 3

Fig. 3

FcRn targeted nanoparticles can be seen as red puncta in the confocal fluorescence images of sections of mouse duodenum (left panel). Comparison of organ localization of FcRn targeted and non-targeted PLA-PEG nanoparticles (right panel). Reproduced with permission from [136].

Fig. 4

Fig. 4

(A) Synthesis of TPP end capped and QD functionalized PLGA-PEG block copolymers. (B) Schematic illustration of drug loaded targeted nanoparticles. (C) Modulation of size and zeta potential. (D) TEM images of the fabricated nanoparticles. (E) IL-6 and TNF-α secretion profiles of nanoparticles with different zeta potentials (left) and diameters (right). Reproduced with permission from [196].

Fig. 5

Fig. 5

TEM images revealing the effect of the number of L-lysine units on the vector shape (left). A comparison of DNA uptake capacity of pHK10 and pHK15 (middle) and gene expression (right). Reprinted with permission from [198]. Copyright (2013) American Chemical Society.

Fig. 6

Fig. 6

(A) Scanning electron microscopic images of cytoplasmic (upper) and nucleoplasmic sides of nuclear envelope revealing the NPCs. (B) Schematic depiction of receptor mediated transportation across the NPCs. (C) Immunoelectron microscopic image of gold nanoparticles translocation between nucleus (n) and cytoplasm (c). Reproduced with permission from [207].

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