An optimized ionizable cationic lipid for brain tumor-targeted siRNA delivery and glioblastoma immunotherapy

Liu, Shuhan; Liu, Ji; Li, Haisong; Mao, Kuirong; Wang, Haorui; Meng, Xiandi; Wang, Jialiang; Wu, Chenxi; Chen, Hongmei; Wang, Xin; Cong, Xiuxiu; Hou, Yue; Wang, Ye; Wang, Ming; Yang, Yong-Guang; Sun, Tianmeng

doi:10.1016/j.biomaterials.2022.121645

Cited by 54 publications

(46 citation statements)

References 62 publications

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“…The electrostatic interactions between ILNPs and the negative surface of the endosomal lumen are further promoted, which can accelerate the fusion of ILNPs with the cell membrane. The cell uptake can be enhanced and the completion of the uptake process facilitated [ 134 ]. Specifically, The IDDSs based on DODMA to deliver siRNA in cells are widely studied.…”

Section: Delivery Mechanisms Of Iddssmentioning

confidence: 99%

“…Some studies have shown that most nanoparticles are difficult to be released into the cytoplasm after entering endolysosomes [ 136 – 138 ]. ILNPs play an important role in delivering nucleic acid drugs to cells [ 134 ]. During cellular uptake, the formation of cellular vesicles (early endosomes) with a pH between 5.5 and 6.2 is required to engulf ILNPs.…”

Section: Delivery Mechanisms Of Iddssmentioning

confidence: 99%

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Ionizable drug delivery systems for efficient and selective gene therapy

Zhang

Guo²,

Chen³

et al. 2023

Military Med Res

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Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function. However, a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells. To be excited, the development of ionizable drug delivery systems (IDDSs) has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019 (COVID-19) in 2021. Compared with conventional cationic gene vectors, IDDSs can decrease the toxicity of carriers to cell membranes, and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures. Despite the progress, there remain necessary requirements for designing more efficient IDDSs for precise gene therapy. Herein, we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms. The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of pDNA and four kinds of RNA. In particular, organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity. We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future, and indicate ideas for developing next generation gene vectors.

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Section: Delivery Mechanisms Of Iddssmentioning

confidence: 99%

Section: Delivery Mechanisms Of Iddssmentioning

confidence: 99%

Ionizable drug delivery systems for efficient and selective gene therapy

Zhang

Guo²,

Chen³

et al. 2023

Military Med Res

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show abstract

“…The regulation of the tumor microenvironment of GBM multiforme with the ILNP showed promising results and holds potential for the treatment of other brain tumors. [31] 4.1.2 | Messenger RNA (mRNA)…”

Section: Small Interfering Rna (Sirna)mentioning

confidence: 99%

“…developed an ILNP that effectively delivers siRNA to the mouse brain by optimizing the chemical and physical properties of the ILNP. The regulation of the tumor microenvironment of GBM multiforme with the ILNP showed promising results and holds potential for the treatment of other brain tumors [31] …”

Section: The Application Of Ins In Treating Brain Diseasesmentioning

confidence: 99%

Nucleic acid delivery by ionizable nanocarriers for brain disease treatment

Xiong

Ling

Zhang

et al. 2023

Brain-X

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The successful application of messenger RNA vaccines in the market has demonstrated the potential of gene therapy in treating various diseases, including infectious diseases, autoimmune disorders, brain diseases, and other cancers. However, gene therapy faces great challenges in treating brain diseases such as brain tumors, infections, and strokes because the limitations of the blood-brain barrier make it difficult for nucleic acid drugs to be delivered safely and effectively into the brain. Therefore, there is a high demand for carriers delivering nucleic acid drugs to the brain. Ionizable nanocarriers (INs) have great advantages in gene therapy due to their pH-responsive properties, which facilitate the safe and efficient delivery of targets, responsive release in the disease microenvironment, and the protection of nucleic acids from degradation. To better understand INs and their potential as therapeutic vectors for brain diseases, the present review describes their biological properties, recent progress in the field, and promising applications. In particular, the related prospects and challenges are discussed to promote the further development of INs. K E Y W O R D S blood-brain barrier (BBB), brain diseases, ionizable nanocarriers (INs), nucleic acidsThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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“…32 The incorporation of disulfide bond into lipid nanoparticles can enhance gene delivery efficiency by promoting lipid degradation and intracellular release of therapeutic cargos via the thiol-disulfide exchange reaction in response to the upregulated reduced glutathione (GSH) in tumor cells. 33,34 Using a lipid screening approach by delivering DNA encoding green fluorescent protein (GFP), we have identified PPPDA-O16B, synthesized from N-Propyl-1,3-propanediamine (PPPDA) and 2-(dodecyldisulfanyl) ethyl acrylate (O16B) as a leading lipid for DNA delivery from a library containing 16 lipids. Detailed study revealed that PPPDA-O16B can encapsulate DNA plasmid, releasing DNA selectively via lipid degradation catalyzed by GSH.…”

Section: Introductionmentioning

confidence: 99%