Targeted and effective glioblastoma therapy via aptamer-modified tetrahedral framework nucleic acid-paclitaxel nanoconjugates that can pass the blood brain barrier

Sirong Shi; Wei Fu; Shiyu Lin; Taoran Tian; Songhang Li; Xiaoru Shao; Yuxin Zhang; Tao Zhang; Zisheng Tang; Yi Zhou; Yunfeng Lin; Xiaoxiao Cai

doi:10.1016/j.nano.2019.102061

Targeted and effective glioblastoma therapy via aptamer-modified tetrahedral framework nucleic acid-paclitaxel nanoconjugates that can pass the blood brain barrier

Nanomedicine. 2019 Oct:21:102061. doi: 10.1016/j.nano.2019.102061. Epub 2019 Jul 22.

Authors

Sirong Shi¹, Wei Fu², Shiyu Lin¹, Taoran Tian¹, Songhang Li¹, Xiaoru Shao¹, Yuxin Zhang¹, Tao Zhang¹, Zisheng Tang³, Yi Zhou⁴, Yunfeng Lin¹, Xiaoxiao Cai⁵

Affiliations

¹ State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
² Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, China.
³ Department of Endodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
⁵ State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address: xcai@scu.edu.cn.

PMID: 31344499
DOI: 10.1016/j.nano.2019.102061

Abstract

Targeted DNA nanoparticles have been identified as one of the most promising nanocarriers in anti-glioma drug delivery. We established a multifunctional nanosystem for targeted glioma therapy. Tetrahedral framework nucleic acid (tFNA), entering U87MG cells and bEnd.3 cells, was chosen to deliver two aptamers, GMT8 and Gint4.T, and paclitaxel. GMT8 and Gint4.T, which specifically bind with U87MG cells and with PDGFRβ, were linked with tFNA, to form Gint4.T-tFNA-GMT8 (GTG). GTG was efficiently internalized by U87MG and bEnd.3 cells and penetrated an in-vitro blood-brain-barrier model. GTG loaded with paclitaxel (GPC) had potentiated anti-glioma efficacy. It inhibited the proliferation, migration, and invasion of U87MG cells, and enhanced apoptosis induction in these cells. The expression of apoptosis-related proteins was significantly changed after treatment with GPC, confirming apoptosis induction. Our study demonstrated that the combination of GTG and paclitaxel has great potential for glioma treatment and tFNA shows great promise for use in drug delivery.

Keywords: Gint4.T-tFNA-GMT8; Gint4.T-tFNA-GMT8/paclitaxel complexes; Glioblastoma multiforme; Tetrahedral framework nucleic acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Aptamers, Nucleotide* / chemistry
Aptamers, Nucleotide* / pharmacokinetics
Aptamers, Nucleotide* / pharmacology
Blood-Brain Barrier* / metabolism
Blood-Brain Barrier* / pathology
Brain Neoplasms* / drug therapy
Brain Neoplasms* / metabolism
Brain Neoplasms* / pathology
Cell Line, Tumor
Glioblastoma* / drug therapy
Glioblastoma* / metabolism
Glioblastoma* / pathology
Humans
Nanoconjugates* / chemistry
Nanoconjugates* / therapeutic use
Paclitaxel* / chemistry
Paclitaxel* / pharmacokinetics
Paclitaxel* / pharmacology
Rats

Substances

Aptamers, Nucleotide
Nanoconjugates
Paclitaxel