The Importance of Apparent pKa in the Development of Nanoparticles Encapsulating siRNA and mRNA

被引：138
作者：
Patel, Pratikkumar [1 ]
Ibrahim, Nurudeen Mohammed [1 ]
Cheng, Kun [1 ]
机构：
[1] Univ Missouri, Sch Pharm, Div Pharmacol & Pharmaceut Sci, 2464 Charlotte St, Kansas City, MO 64108 USA
来源：
TRENDS IN PHARMACOLOGICAL SCIENCES | 2021年 / 42卷 / 06期
基金：
美国国家卫生研究院;
关键词：
LIPID-LIKE MATERIALS; IN-VIVO; SYSTEMIC DELIVERY; ENDOSOMAL ESCAPE; TRANSFECTION; EFFICIENCY; CHITOSAN; POLYETHYLENIMINE; TRAFFICKING; VACCINES;
D O I：
10.1016/j.tips.2021.03.002
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Polymer and lipid nanoparticles have been extensively used as carriers to address the biological barriers encountered in siRNA and mRNA delivery. We summarize the crucial role of nanoparticle charge and ionizability in complexing RNAs, binding to biological components, escaping from the endosome, and releasing RNAs into the cytoplasm. We highlight the significant impact of the apparent pKa of nanoparticles on their efficacy and toxicity, and the importance of optimizing pKa in the development of lead formulations for RNAs. We also discuss the feasibility of fine-tuning the pKa in nanoparticles and the applications of this approach in the optimization of delivery systems for RNAs.
引用
收藏
页码：448 / 460
页数：13
相关论文
共 90 条
  • [61] Efficiency of Chitosan/Hyaluronan-Based mRNA Delivery Systems In Vitro: Influence of Composition and Structure
    Soliman, Ousamah Younoss
    Alameh, Mohamad Gabriel
    De Cresenzo, Gregory
    Buschmann, Michael D.
    Lavertu, Marc
    [J]. JOURNAL OF PHARMACEUTICAL SCIENCES, 2020, 109 (04) : 1581 - 1593
  • [62] Combination antitumor immunotherapy with VEGF and PIGF siRNA via systemic delivery of multi-functionalized nanoparticles to tumor-associated macrophages and breast cancer cells
    Song, Yudong
    Tang, Cui
    Yin, Chunhua
    [J]. BIOMATERIALS, 2018, 185 : 117 - 132
  • [63] Enhanced stability and gene silencing ability of siRNA-loaded polyion complexes formulated from polyaspartamide derivatives with a repetitive array of amino groups in the side chain
    Suma, Tomoya
    Miyata, Kanjiro
    Ishii, Takehiko
    Uchida, Satoshi
    Uchida, Hirokuni
    Itaka, Keiji
    Nishiyama, Nobuhiro
    Kataoka, Kazunori
    [J]. BIOMATERIALS, 2012, 33 (09) : 2770 - 2779
  • [64] Noncovalent tagging of siRNA with steroids for transmembrane delivery
    Tai, Wanyi
    Gao, Xiaohu
    [J]. BIOMATERIALS, 2018, 178 : 720 - 727
  • [65] POLYELECTROLYTE TITRATION USING FLUORESCENT INDICATOR .1. DIRECT TITRATION OF ANIONIC AND CATIONIC POLYELECTROLYTES WITH 10(-4)N STANDARD SOLUTIONS
    TANAKA, H
    SAKAMOTO, Y
    [J]. JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY, 1993, 31 (11) : 2687 - 2691
  • [66] Recent Development of pH-Responsive Polymers for Cancer Nanomedicine
    Tang, Houliang
    Zhao, Weilong
    Yu, Jinming
    Li, Yang
    Zhao, Chao
    [J]. MOLECULES, 2019, 24 (01)
  • [67] Tang X., 2010, FRONT ONCOL, V9, P1208
  • [68] Leading RNA Interference Therapeutics Part 1: Silencing Hereditary Transthyretin Amyloidosis, with a Focus on Patisiran
    Titze-de-Almeida, Simoneide S.
    de Paula Brandao, Pedro Renato
    Faber, Ingrid
    Titze-de-Almeida, Ricardo
    [J]. MOLECULAR DIAGNOSIS & THERAPY, 2020, 24 (01) : 49 - 59
  • [69] THE INTRINSIC PKA VALUES FOR PHOSPHATIDYLSERINE AND PHOSPHATIDYLETHANOLAMINE IN PHOSPHATIDYLCHOLINE HOST BILAYERS
    TSUI, FC
    OJCIUS, DM
    HUBBELL, WL
    [J]. BIOPHYSICAL JOURNAL, 1986, 49 (02) : 459 - 468
  • [70] Odd-Even Effect of Repeating Aminoethylene Units in the Side Chain of N-Substituted Polyaspartamides on Gene Transfection Profiles
    Uchida, Hirokuni
    Miyata, Kanjiro
    Oba, Makoto
    Ishii, Takehiko
    Suma, Tomoya
    Itaka, Keiji
    Nishiyama, Nobuhiro
    Kataoka, Kazunori
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2011, 133 (39) : 15524 - 15532
123456789