Abstract
Nucleic acid-based macromolecules, including protein-expressing plasmid DNA (pDNA) and messenger RNA (mRNA), antisense oligonucleotides (ASOs), small interfering RNA (siRNA), genome editing systems, and so on, have paved new avenues for the development of therapeutic interventions against various types of diseases. Several nucleic acid-based drug have been approved for clinical application, and many more are under clinical evaluation. However, it should be noted that their clinical translation is dependent on the successful delivery to the target site and cells. Among these formulations, the clinically validated polylactide (PLA)-based nanocarriers have attracted wide attention. Unfortunately, PLA nanocarriers inefficiently encapsulated nucleic acid. In this regard, a cationic lipid-assisted PEG-b-PLA nanoparticle (CLAN) is explored to high efficiently encapsulate nucleic acid drug inside its aqueous core through double emulsion method. In this protocol, siRNA is used as a model nucleic acid drug, and the preparation and characterization of siRNA-loaded CLAN are described. And, all nucleic acid drugs could be loaded into the CLAN formulation with the same procedures. The present results demonstrate that the CLAN formulation displayed an extreme high encapsulation efficiency (>95%), an efficient cellular uptake of siRNA-loaded CLAN by tumor cells, and thereby improving the downregulation of targeted gene in vitro and in tumor models.
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References
Akinc A, Maier MA, Manoharan M, Fitzgerald K, Jayaraman M, Barros S, Ansell S, Du XY, Hope MJ, Madden TD, Mui BL, Semple SC, Tam YK, Ciufolini M, Witzigmann D, Kulkarni JA, Van Der Meel R, Cullis PR (2019) The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat Nanotechnol 14(12):1084–1087
Anzalone AV, Koblan LW, Liu DR (2020) Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors. Nat Biotechnol 38(7):824–844
Cun DM, Foged C, Yang MS, Frokjaer S, Nielsen HM (2010) Preparation and characterization of poly(DL-lactide-co-glycolide) nanoparticles for siRNA delivery. Int J Pharm 390(1):70–75
Ding SK, Serra CA, Vandamme TF, Yu W, Anton N (2019) Double emulsions prepared by two-step emulsification: history, state-of-the-art and perspective. J Control Release 295:31–49
Dominici JT, Clark S, Scheetz J, Eleazer PD (2005) Analysis of heat generation using ultrasonic vibration for post removal. J Endod 31(4):301–303
Friedmann T, Roblin R (1972) Gene therapy for human genetic disease? Science 175(4025):949–955
Hoy SM (2018) Patisiran: first global approval. Drugs 78(15):1625–1631
Jilek S, Merkle HP, Walter E (2005) DNA-loaded biodegradable microparticles as vaccine delivery systems and their interaction with dendritic cells. Adv Drug Deliver Rev 57(3):377–390
Khurana A, Allawadhi P, Khurana I, Allwadhi S, Weiskirchen R, Banothu AK, Chhabra D, Joshi K, Bharani KK (2021) Role of nanotechnology behind the success of mRNA vaccines for COVID-19. Nano Today 38:101142
Kong A (1963) Possible integration of viral nucleic acid into the genome of animal cells. Prog Med Virol 5:169–218
Luu YK, Kim K, Hsiao BS, Chu B, Hadjiargyrou M (2003) Development of a nanostructured DNA delivery scaffold via electrospinning of PLGA and PLA-PEG block copolymers. J Control Release 89(2):341–353
Lv HT, Zhang SB, Wang B, Cui SH, Yan J (2006) Toxicity of cationic lipids and cationic polymers in gene delivery. J Control Release 144(1):100–109
Moghimi SM, Patel HM (1998) Serum-mediated recognition of liposomes by phagocytic cells of the reticuloendothelial system – the concept of tissue specificity. Adv Drug Deliver Rev 32(1–2):45–60
Murata N, Takashima Y, Toyoshima K, Yamamoto M, Okada H (2008) Anti-tumor effects of anti-VEGF siRNA encapsulated with PLGA microspheres in mice. J Control Release 126(3):246–254
Opalinska JB, Gewirtz AM (2002) Nucleic-acid therapeutics: basic principles and recent applications. Nat Rev Drug Discov 1(7):503–514
Patil Y, Panyam J (2009) Polymeric nanoparticles for siRNA delivery and gene silencing. Int J Pharm 367(1–2):195–203
Rogers S, Lowenthal A, Terheggen HG, Columbo JP (1973) Induction of arginase activity with the Shope papilloma virus in tissue culture cells from an argininemic patient. J Exp Med 137(4):1091–1096
Setten RL, Rossi JJ, Han SP (2019) The current state and future directions of RNAi-based therapeutics. Nat Rev Drug Discov 18(6):421–446
Singh M, Briones M, Ott G, O’Hagan D (2000) Cationic microparticles: a potent delivery system for DNA vaccines. Proc Natl Acad Sci U S A 97(2):811–816
Van Den Berg AIS, Yun CO, Schiffelers RM, Hennink WE (2021) Polymeric delivery systems for nucleic acid therapeutics: approaching the clinic. J Control Release 331:121–141
Yang XZ, Dou S, Sun TM, Mao CQ, Wang HX, Wang J (2011) Systemic delivery of siRNA with cationic lipid assisted PEG-PLA nanoparticles for cancer therapy. J Control Release 156(2):203–211
Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG (2014) Non-viral vectors for gene-based therapy. Nat Rev Genet 15(8):541–555
Zuckerman JE, Gritli I, Tolcher A, Heidel JD, Lim D, Morgan R, Chmielowski B, Ribas A, Davis ME, Yen Y (2014) Correlating animal and human phase la/lb clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA. Proc Natl Acad Sci U S A 111(31):11449–11454
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Zhao, L., Yang, X. (2022). Development of Cationic Lipid-Assisted PEG-b-PLA Nanoparticle for Nucleic Acid Therapeutics. In: Tian, H., Chen, X. (eds) Gene Delivery. Biomaterial Engineering. Springer, Singapore. https://doi.org/10.1007/978-981-16-5419-0_29
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DOI: https://doi.org/10.1007/978-981-16-5419-0_29
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