A holistic analysis of the intrinsic and delivery-mediated toxicity of siRNA therapeutics

Ranjbar, Sheyda; Zhong, Xiao-bo; Manautou, José; Lu, Xiuling

doi:10.1016/j.addr.2023.115052

Cited by 14 publications

(4 citation statements)

References 176 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Organ toxicity is a major concern of liposomal nanodrugs [ 230 ] because they prefer to accumulate in certain organs, such as the liver and spleen, affecting the tissue-specific functionality and potentially causing toxicities [ 231 ]. In addition, liposomes may interact with cell membranes, which can alter cell permeability and integrity, ultimately causing cellular damage [ 232 ]. Addressing these safety concerns requires strategic refinement and optimization.…”

Section: Discussion and Outlookmentioning

confidence: 99%

Lipid-Based Nanotechnology: Liposome

Jiang,

Li,

Wang

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

Over the past several decades, liposomes have been extensively developed and used for various clinical applications such as in pharmaceutical, cosmetic, and dietetic fields, due to its versatility, biocompatibility, and biodegradability, as well as the ability to enhance the therapeutic index of free drugs. However, some challenges remain unsolved, including liposome premature leakage, manufacturing irreproducibility, and limited translation success. This article reviews various aspects of liposomes, including its advantages, major compositions, and common preparation techniques, and discusses present U.S. FDA-approved, clinical, and preclinical liposomal nanotherapeutics for treating and preventing a variety of human diseases. In addition, we summarize the significance of and challenges in liposome-enabled nanotherapeutic development and hope it provides the fundamental knowledge and concepts about liposomes and their applications and contributions in contemporary pharmaceutical advancement.

show abstract

Section: Discussion and Outlookmentioning

confidence: 99%

Lipid-Based Nanotechnology: Liposome

Jiang,

Li,

Wang

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…However, the naked delivery of siRNA has faced many challenges because of their inherent properties-i.e. high molecular weight and negative charge (make them difficult to enter into cells), instability in plasma, immunogenicity, intrinsic toxicity and so on [104][105][106]. Besides, the major barriers for siRNA-based RNAi are depending upon two major factors: (i) the area-of-therapeutic interest-that can be specific tissues or organs-whose accessibility can pose an issue for reaching of siRNA; and (ii) the administration routes (local and systemic)-herein, the local administration route can pose comparative lesser threat.…”

Section: Conventional Delivery and Challengesmentioning

confidence: 99%

Inorganic nanocarriers for siRNA delivery for cancer treatments

Kandasamy,

Maity

2024

Biomed. Mater.

View full text Add to dashboard Cite

RNA interference (RNAi) is one of the emerging methodologies utilized in the treatment of a wide variety of diseases including cancer. This method specifically uses therapeutic RNAs (TpRNAs) like small interfering RNAs (siRNAs) to regulate/silence the cancer-linked genes, thereby minimizing distinct activities of cancer cells and aiding in their apoptosis. But, many complications arise during the transport/delivery of these TpRNAs that include poor systemic circulation, instability/degradation inside the body environment, no targeting capacity and also low cellular internalization. These difficulties can be overcome by using nanocarriers to deliver the TpRNAs inside the cancer cells. The following are the various categories of nanocarriers - viral vectors (e.g., lentivirus and adenovirus) and non-viral nanocarriers (self-assembling nanocarriers and inorganic nanocarriers). Viral vectors suffer from few disadvantages like high immunogenicity as compared to the non-viral nanocarriers. Among non-viral nanocarriers, inorganic nanocarriers gained significant attention as their inherent properties (like magnetic properties) can aid in effective cellular delivery of the TpRNAs. Most of the prior reports have discussed about the delivery of TpRNAs through self-assembling nanocarriers; however very few have reviewed about their delivery using the inorganic nanoparticles. Therefore, in this review, we have mainly discussed the delivery of TpRNAs – i.e., siRNA, especially programmed death ligand-1 (PD-L1), survivin, B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor (VEGF) and other siRNAs using the inorganic nanoparticles – mainly magnetic, metal and silica nanoparticles. Moreover, we have discussed about the combined delivery of these TpRNAs along with chemotherapeutic drugs (mainly doxorubicin) and in vitro and in vivo therapeutic effectiveness.

show abstract

“…[95] Although being used most frequently as the carrier for siRNA drugs in the clinical trials, numerous LNP-based siRNA drugs such as TKM-ApoB and TKM-080301 have failed in clinical trials due to the safety issue rather than the silencing efficiency. [381] Accordingly, there are still a lot of challenges associated with LNP-based siRNA drugs. Of the challenges, de-livering to the target organs other than liver and encountering in vivo cytotoxicity are considered the major two obstacles need to be addressed.…”

Section: Recent Advances and Design Strategies Of Clinical-used Sirna...mentioning

confidence: 99%

Recent Advances in Engineering Carriers for siRNA Delivery

Yang,

Lin,

Zhang

et al. 2024

Macromolecular Bioscience

View full text Add to dashboard Cite

RNA interference (RNAi) technology has been a promising treatment strategy for combating intractable diseases. However, the applications of RNAi in clinical were hampered by extracellular and intracellular barriers. To overcome these barriers, various siRNA delivery systems have been developed in the past two decades. The first approved RNAi therapeutic, Patisiran (ONPATTRO™) using lipids as the carrier, for the treatment of amyloidosis is one of the most important milestones. This has greatly encouraged researchers to work on creating new functional siRNA carriers. In this review, we summarized the recent advances in siRNA carriers consisting of lipids, polymers, and polymer‐modified inorganic particles for cancer therapy. Representative examples are presented to show the structural design of the carriers in order to overcome the delivery hurdles associated with RNAi therapies. Finally, the existing challenges and future perspective for developing RNAi as a clinical modality will be discussed and proposed. We believe that the addressed contributions in this review will promote the development of siRNA delivery systems for future clinical applications.This article is protected by copyright. All rights reserved

show abstract

A holistic analysis of the intrinsic and delivery-mediated toxicity of siRNA therapeutics

Cited by 14 publications

References 176 publications

Lipid-Based Nanotechnology: Liposome

Lipid-Based Nanotechnology: Liposome

Inorganic nanocarriers for siRNA delivery for cancer treatments

Recent Advances in Engineering Carriers for siRNA Delivery

Contact Info

Product

Resources

About