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

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
• nanoformulations
• cancer
• neurodegenerative disorder
• hepatic disorder
• drug delivery

Acknowledgement

All the authors acknowledge CARE for infrastructural and financial support. PP acknowledges CARE for providing fellowship.

Disclosure statement

The authors report there are no competing interests to declare.

Authors contribution

KG collected data and prepared the initial draft, PP was involved in the preparation of drawings, and AG was involved in the conception, designing, and additional data collection, analysis, and final manuscript preparation. All the listed authors approved the final draft.

Data availability statement

All the data are available in the manuscript.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.