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Review
. 2023 Dec;30(1):2284684.
doi: 10.1080/10717544.2023.2284684. Epub 2023 Nov 21.

Intricate subcellular journey of nanoparticles to the enigmatic domains of endoplasmic reticulum

Koyeli Girigoswami  1 , Pragya Pallavi  1 , Agnishwar Girigoswami  1
Affiliations
Review

Intricate subcellular journey of nanoparticles to the enigmatic domains of endoplasmic reticulum

Koyeli Girigoswami et al. Drug Deliv. 2023 Dec.

Abstract

It is evident that site-specific systemic drug delivery can reduce side effects, systemic toxicity, and minimal dosage requirements predominantly by delivering drugs to particular pathological sites, cells, and even subcellular structures. The endoplasmic reticulum (ER) and associated cell organelles play a vital role in several essential cellular functions and activities, such as the synthesis of lipids, steroids, membrane-associated proteins along with intracellular transport, signaling of Ca2+, and specific response to stress. Therefore, the dysfunction of ER is correlated with numerous diseases where cancer, neurodegenerative disorders, diabetes mellitus, hepatic disorder, etc., are very common. To achieve satisfactory therapeutic results in certain diseases, it is essential to engineer delivery systems that can effectively enter the cells and target ER. Nanoparticles are highly biocompatible, contain a variety of cargos or payloads, and can be modified in a pliable manner to achieve therapeutic effectiveness at the subcellular level when delivered to specific organelles. Passive targeting drug delivery vehicles, or active targeting drug delivery systems, reduce the nonselective accumulation of drugs while reducing side effects by modifying them with small molecular compounds, antibodies, polypeptides, or isolated bio-membranes. The targeting of ER and closely associated organelles in cells using nanoparticles, however, is still unsymmetrically understood. Therefore, here we summarized the pathophysiological prospect of ER stress, involvement of ER and mitochondrial response, disease related to ER dysfunctions, essential therapeutics, and nanoenabled modulation of their delivery to optimize therapy.

Keywords: ER stress; cancer; drug delivery; hepatic disorder; nanoformulations; neurodegenerative disorder.

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Conflict of interest statement

The authors report there are no competing interests to declare.

Figures

Figure 1.
Figure 1.
Schematic representation of structure and function of endoplasmic reticulum and mitochondria.
Figure 2.
Figure 2.
The major roles of endoplasmic reticulum and route to ER stress dependant unfolded protein response.
Figure 3.
Figure 3.
The diagram focuses on how UPR functions in cancer and how they are affected by extrinsic stress that can lead to protein folding in the endoplasmic reticulum.
Figure 4.
Figure 4.
Schematically represented how the lipids, proteins, and calcium are metabolized and homeostasized by the ER due to direct or indirect communication with other cell organelles.
Figure 5.
Figure 5.
Targeting ER stress and UPR to control neurodegenerative disorder.
Figure 6.
Figure 6.
Amphiphilic structure of lipid molecules to formulate nanoparticles.
Figure 7.
Figure 7.
Schematic description of transportation of nanoparticles.
See this image and copyright information in PMC

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