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Nanoparticle-Mediated Small RNA Deliveries for Molecular Therapies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Ramasamy Paulmurugan, Uday Kumar Sukumar, Tarik F. Massoud
In one study, a lipoplex for delivering siRNA targeting VE-cadherin in the endothelial cells was developed by using E-selectin targeted antibody conjugated cationic lipid (anti-E-selectin–SAINT lipoplex (SAINTarg)). It effectively transfected human umbilical vein endothelial cells (HUVECs) and showed biological function by downregulating E-cadherin expression [8]. Lipids such as 1,2-di-O-octadecenyl-3-trimethylammonium (DOTMA), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and dioleoylphosphatidylethanolamine (DOPE) are commonly used for making lipoplexes for transfection of nucleic acids, including siRNAs. Addition of cholesterol to lipoplexes makes these lipids deliver the loaded siRNAs into cells without encountering endosomes. This process is also called a fusogenic delivery mechanism [9]. PEGylated DC-Chol/DOPE liposomes loaded with siRNA targeting kinesin spindle protein (KSP) has shown an enhanced anticancer property against ovarian cancer in a preclinical mouse model without activating the immune system [10]. The use of polyethylene glycol (PEG) with lipids in lipoplex preparations has shown improved biodistribution of loaded siRNAs in the circulation, which facilitated improved tumor specific uptake in vivo. However, the use of PEG in lipoplexes can reduce the amount of siRNAs that can be complexed with the lipids [11].
siRNA Delivery for Therapeutic Applications Using Nanoparticles
Published in Yashwant Pathak, Gene Delivery, 2022
Several lipid-based transfection agents are commercially available and are being used in vivo to study the mechanism and effects of siRNA delivery in mammalian cells. These include jetSi-ENDO, Lipofectamine RNAiMAX, siPORT NeoFX, DharmaFECT, X-tremeGENE, and TriFECTin. DOTAP, 1,2-dioleoyl-3-trimethylammonium-propane, and their in vivo siRNA delivery has been examined. Recently, a combinatorial library has been implemented for one by one screening and synthesis of cationic lipids for siRNA delivery. Lipidoid was developed for the efficient delivery of siRNA to the cells. It known as a combinatorial library of 1200 lipid like materials, which synthesize to primary or secondary amine with conjugation with alkyl-acrylates or alkyl-acrylamides. A number of materials were identified to substantially improve silencing over delivery of naked siRNA in vitro and in vivo in mice, rats, and nonhuman primates [15].
Organic Nanocarriers for Brain Drug Delivery
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
Marlene Lúcio, Carla M. Lopes, Eduarda Fernandes, Hugo Gonẹalves, Maria Elisabete C. D. Real Oliveira
Other advantages of liposomes, as potential ONCs for brain drug delivery, are related to their very adjustable properties which may change with size, preparation method and lipid composition, which also defines the type of charge and charge density of the liposomal surface [2, 65, 66]. In terms of brain delivery, it may be beneficial to include cationic lipids, such as 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), dioctadecyldimethylammonium bromide (DODAB) or dioctadecyldimethylammonium chloride (DODAC), in the composition of the liposomes, rendering them with a positively charged surface. Cationic liposomes cross the BBB through the AMT mechanism [2, 14, 75, 76]. Moreover, cationic liposomes may also be used as transfection carriers to deliver genetic material into the cells, avoiding lysosomal digestion [77]. In this case, besides bearing cationic lipids, liposomes are also composed of neutral-charged helper lipids, like 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or monoolein, with fusogenic properties [77, 78]. These nucleic acid-loaded NCs, called lipoplexes, are formed by nucleic acid complexation and compaction, a process which initiates with electrostatic interaction between the cationic liposomal surface and anionic phosphate groups in nucleic acid material [77] (Fig. 4.4).
Negatively charged phospholipids doped liposome delivery system for mRNA with high transfection efficiency and low cytotoxicity
Published in Drug Delivery, 2023
Lin Wang, Huanchun Xing, Shuai Guo, Wenbin Cao, Zinan Zhang, Lijuan Huang, Sui Xin, Yuan Luo, Yongan Wang, Jun Yang
Traditional liposome (Figure 1) consists of cationic lipids, electrically neutral auxiliary phospholipids, cholesterol, and phospholipids containing polyethylene glycol (PEG) (Liu et al., 2021). The most classic and highly efficient cationic lipid, 1,2-Dioleoyl-3-trimethylammonium-propane (DOTAP), was chosen as the core cation component of the liposome to guarantee effective transfection (Simberg et al., 2004). In previous reports, electrically neutral 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) were applied as auxiliary phospholipids to form the skeleton of liposomes (Cheng & Lee, 2016; Yanez Arteta et al., 2018). However, in this study, phosphatidyl serine (PS) was applied to replace DOPE or DSPC for increasing the safety of the system because the PS as a negatively charged phospholipids can neutralize part of the positive charge of DOTAP (Zhao et al., 2022) and reduce the overall charge of the particle (Figure 1). EGFP mRNA was chosen as targeted mRNA loaded by liposome due to the accessibility of the fluorescence of EGFP expressed by the mRNA (Baeken & Yokobayashi, 2022; Larson et al., 2022).
Polysialic acid-functionalized liposomes for efficient honokiol delivery to inhibit breast cancer growth and metastasis
Published in Drug Delivery, 2023
Xin Li, Shuang Guan, Henan Li, Dong Li, Dan Liu, Jing Wang, Wenquan Zhu, Guihua Xing, Liling Yue, Defu Cai, Qi Zhang
HNK was purchased from Dalian Meilun Biotech Co., Ltd. (Dalian, China). Egg yolk phosphatidylcholine (EPC) was provided by LIPOID GmbH Ludwigshafen, Germany. 1, 2-Dioleoyl-3-trimethylammonium-propane (chloride salt) (DOTAP) and dioleoyl phosphoethanolamine (DOPE) were supplied by Xi’an Ruixi Biological Technology Co., Ltd. (Xi’an, China). PSA (with MW of 80 kDa) were produced by Zhenjiang Changxing Pharmaceutical Co., Ltd. Cholesterol, Sephadex G-50, coumarin-6 (Cou6), Hoechst 33258, sulforhodamine B (SRB), tri-chloroacetic acid (TCA), and Tris base were all purchased from Sigma-Aldrich (Shanghai, China). The fluorometric TUNEL apoptosis detection kit was purchased from Promega (Wisconsin, USA). RPMI-1640 medium and penicillin–streptomycin were obtained from Macgene (Beijing, China). Fetal bovine serum (FBS) was purchased from Wisent (Nanjing, China).
Emergence of mRNA vaccines in the management of cancer
Published in Expert Review of Vaccines, 2023
Mohamad Irfan Mohamad Razif, Nabilah Nizar, Nur Hannah Zainal Abidin, Syasya Nasuha Muhammad Ali, Wan Nurul Najihah Wan Zarimi, Junaidi Khotib, Deny Susanti, Muhammad Taufiq Mohd Jailani, Muhammad Taher
These parenteral routes have different effectiveness in activation of immune cells as different injection sites would have different levels of immune cells, APCs, and DCs. Based on an independent study, subcutaneous and intramuscular routes displayed no difference in antibody activation. Theoretically, administration via subcutaneous route should elicit higher level of immunogenic effect than intramuscular due to the fact that dermis contains higher number of immune cells compared to muscle tissue [45]. For example, when HIV gp140 surface glycoprotein-encoding saRNA vaccination formulated with LNP based on the ionizable lipid DLin-DMA was tested for its immunogenicity with different route of administration, IM route is more effective when compared with the ID and SC routes but there was no significant difference between IM and ID routes. In another experiment, HA-mRNA-LNP vaccine was used, and HAI titers were considerably higher in ID route than IM route. However, 2 weeks after vaccination boost, it was found that both administration routes had similar yields [46]. In addition to the parenteral route, nebulization of mRNA encapsulated in 1,2-Dioleoyl-3-trimethylammonium propane-based LNP was demonstrated in an animal study. The study found that the nebulization approach had no influence on the mRNA integrity or the efficiency of encapsulation [47].