AMP functionalized curdlan nanoparticles as a siRNA carrier: Synthesis, characterization and targeted delivery via adenosine A2B receptor

Qingming Bao; Tsogzolmaa Ganbold; Qiburi Qiburi; Mingming Bao; Shuqin Han; Huricha Baigude

doi:10.1016/j.ijbiomac.2021.10.138

AMP functionalized curdlan nanoparticles as a siRNA carrier: Synthesis, characterization and targeted delivery via adenosine A_2B receptor

Int J Biol Macromol. 2021 Dec 15;193(Pt A):866-873. doi: 10.1016/j.ijbiomac.2021.10.138. Epub 2021 Oct 29.

Authors

Qingming Bao¹, Tsogzolmaa Ganbold², Qiburi Qiburi¹, Mingming Bao¹, Shuqin Han³, Huricha Baigude⁴

Affiliations

¹ Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, PR China.
² Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, PR China. Electronic address: Tsogi001@mail.imu.edu.cn.
³ Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, PR China. Electronic address: chem-hshq@imu.edu.cn.
⁴ Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, PR China. Electronic address: hbaigude@imu.edu.cn.

PMID: 34743942
DOI: 10.1016/j.ijbiomac.2021.10.138

Abstract

Receptor-mediated endocytosis has been used for tissue targeted delivery of short interfering RNA (siRNA) drugs. Herein, we investigated adenosine receptor (AR) as a candidate for receptor-mediated siRNA internalization. We synthesized adenosine functionalized cationic curdlan derivatives (denote CuAMP polymers). One of these polymers, CuAMP4, efficiently delivered siRNA to breast cancer cells expressing high level of A_2B receptor. The internalization of siRNA loaded CuAMP4 by cancer cells was inhibited by free AMP as well as endocytosis inhibitors. Moreover, knockdown of A_2BR by siRNA, or pre-treatment of the cells with anti-A_2BR antibody, strongly inhibited the cellular uptake of CuAMP4. Our findings confirmed that A_2BR can be utilized for cell type specific siRNA delivery, and CuAMP4 NP may be a promising delivery system for cancer cell targeted delivery of therapeutic siRNAs.

Keywords: Curdlan; Receptor-mediated endocytosis; siRNA delivery.

MeSH terms

Adenosine Monophosphate / pharmacology*
Animals
Cell Line, Tumor
Humans
Mice
Nanoparticles
RNA, Small Interfering / metabolism
Receptor, Adenosine A2B / metabolism*
beta-Glucans / pharmacology*

Substances

ADORA2B protein, human
RNA, Small Interfering
Receptor, Adenosine A2B
adora2b protein, mouse
beta-Glucans
Adenosine Monophosphate
curdlan