Study and evaluation of mechanisms of dual targeting drug delivery system with tumor microenvironment assays compared with normal assays.
A dual targeting delivery system was developed to completely conquer the two barriers that glioma treatment faces: the blood-brain barrier (BBB) and the brain-glioma barrier. Recently, a system comprising AS1411 aptamer (for glioma targeting) and TGN peptide (for BBB targeting) modified nanoparticles (AsTNPs) was developed, which can effectively target brain glioma and improve the survival of glioma-bearing mice. However, the in vitro models currently used are far too different from the in vivo tumor microenvironment that the glioma targeting delivery system actually faces. In this study, the pharmacology mechanisms of AsTNPs were explored in several models that imitated the tumor microenvironment. AsTNPs can be selectively taken up by endothelial and glioma cells, effectively penetrating the BBB and brain-glioma barriers to reach glioma cells and display their anti-glioma effect. The cell monolayers, tumor spheroids and coculture systems were more suitable in vitro models for the pharmacology evaluation of targeted drug delivery systems.
Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
Huile
H
Gao
Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
Zhi
Z
Yang
Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
Shuang
S
Zhang
Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
Zhiqing
Z
Pang
Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
Qingfeng
Q
Liu
Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. Electronic address: xgjiang@shmu.edu.cn.
Xinguo
X
Jiang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001681:Biological Assay / Q000379:methods*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis / Q000187:drug effects; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000648:ultrastructure; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D013844:Thiazoles / Q000494:pharmacology; D059016:Tumor Microenvironment / Q000187:drug effects
D003374:Coumarins; D013844:Thiazoles; C517282:coumarin 6
Dual drug delivery system; Evaluation model; Glioma; Tumor microenvironment