Title:
NUCLEIC ACID-DRUG CONJUGATE, DRUG DELIVERY SYSTEM, AND PREPARATION METHODS THEREFOR AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2020/150915
Kind Code:
A1
Abstract:
A nucleic acid-drug conjugate based on a phosphorothioate-modified nucleic acid, a drug delivery system, and preparation methods therefor. The nucleic acid-drug conjugate is formed by reacting and binding a phosphorothioate group in a phosphorothioate modified nucleic acid and a group that is modified on a drug molecule and that is capable of experiencing an electrophilic reaction with the phosphorothioate group; in addition, by selecting different nucleic acid sequences comprising functional nucleic acids, the nucleic acid-drug conjugate can self-assemble into various forms of drug-containing nanocarriers for drug delivery. Compared to the prior art, the above nucleic acid-drug conjugate can be achieved by simple solid-phase synthesis technology, and the grafting sites and assembly forms of drug molecules on the nucleic acid backbone can be precisely controlled; in addition, the described method has universality for chemotherapeutic drugs; moreover, the physical and chemical properties as well as the in vivo distribution properties of chemotherapeutic drugs may be significantly improved and the therapeutic effects thereof may be promoted; moreover, the combined treatment of gene therapy and chemotherapy may be achieved.
Inventors:
ZHANG CHUAN (CN)
ZHANG JIAO (CN)
GUO YUANYUAN (CN)
ZHANG JIAO (CN)
GUO YUANYUAN (CN)
Application Number:
PCT/CN2019/072790
Publication Date:
July 30, 2020
Filing Date:
January 23, 2019
Export Citation:
Assignee:
UNIV SHANGHAI JIAOTONG (CN)
International Classes:
A61K31/4745; A61K47/54; A61K45/00; A61P35/00; C07H1/00; C07H21/02
Domestic Patent References:
| WO2014022357A1 | 2014-02-06 |
Foreign References:
| CN108671235A | 2018-10-19 |
Other References:
VEKHOFF, P. ET AL.: "Optimized Synthesis and Enhanced Efficacy of Novel Triplex-Forming Camptothecin Derivatives Based on Gimatecan", BIOCONJUGATE CHEM., vol. 20, 23 March 2009 (2009-03-23), pages 666 - 672, XP055723435, DOI: 20191011145059X
BOUSMAIL, D. ET AL.: "Precision Spherical Nucleic Acids for Delivery of Anticancer Drugs", CHEM. SCI., vol. 8, 31 December 2017 (2017-12-31), pages 6218 - 6229, XP055723438, DOI: 20191011145127X
LI, FANGFEI ET AL.: "A Water-Soluble Nucleolin Aptamer-Paclitaxel Conjugate for Tumor-Specific Targeting in Ovarian Cancer", NATURE COMMUNICATIONS, vol. 8, 31 December 2017 (2017-12-31), pages 1390 - 1403, XP055723439, DOI: 20191011145530A
BOUSMAIL, D. ET AL.: "Precision Spherical Nucleic Acids for Delivery of Anticancer Drugs", CHEM. SCI., vol. 8, 31 December 2017 (2017-12-31), pages 6218 - 6229, XP055723438, DOI: 20191011145127X
LI, FANGFEI ET AL.: "A Water-Soluble Nucleolin Aptamer-Paclitaxel Conjugate for Tumor-Specific Targeting in Ovarian Cancer", NATURE COMMUNICATIONS, vol. 8, 31 December 2017 (2017-12-31), pages 1390 - 1403, XP055723439, DOI: 20191011145530A
Attorney, Agent or Firm:
SHANGHAI HANGSOME INTELLECTUAL PROPERTY LTD (CN)
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