Substance P-modified human serum albumin nanoparticles loaded with paclitaxel for targeted therapy of glioma.
10.1016/j.apsb.2017.09.008
- Author:
Chunhui RUAN
1
;
Lisha LIU
1
;
Yifei LU
1
;
Yu ZHANG
1
;
Xi HE
1
;
Xinli CHEN
1
;
Yujie ZHANG
1
;
Qinjun CHEN
1
;
Qin GUO
1
;
Tao SUN
1
;
Chen JIANG
1
Author Information
1. Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China.
- Publication Type:Journal Article
- Keywords:
BBB, blood–brain barrier;
BBTB, blood–brain tumor barrier;
BCECs, brain capillary endothelial cells;
Blood–brain barrier;
Cou-6, coumarin-6;
D2O, deuterium oxide;
DDS, drug delivery system;
DHO, deuterium hydrogen oxide;
DLS, dynamic light scattering;
Drug delivery;
EE, entrapment efficiency;
FACS, fluorescence-activated cell sorting;
GBM, glioblastoma multiforme;
GSH, glutathione;
Glioma;
HPLC, high performance liquid chromatography;
HSA, human serum albumin;
Human serum albumin;
MAL-PEG-NHS, maleimide-polyethylene glycol-ω-succinimidyl carbonate;
MTT, [4, 5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide;
NK-1, neurokinin-1;
NPs, nanoparticles;
PBS, phosphate-buffered saline;
PI, propidium iodide;
PTX, paclitaxel;
Paclitaxel;
PhAsO, phenylarine oxide;
SP, substance P;
SPARC, secreted protein acidic and rich in cysteine;
Substance P;
TEM, transmission electron microscope;
gp60, glycoprotein 60
- From:
Acta Pharmaceutica Sinica B
2018;8(1):85-96
- CountryChina
- Language:English
-
Abstract:
The blood-brain barrier (BBB) and the poor ability of many drugs to cross that barrier greatly limits the efficacy of chemotherapies for glioblastoma multiforme (GBM). The present study exploits albumin as drug delivery vehicle to promote the chemotherapeutic efficacy of paclitaxel (PTX) by improving the stability and targeting efficiency of PTX/albumin nanoparticles (NPs). Here we characterize PTX-loaded human serum albumin (HSA) NPs stabilized with intramolecular disulfide bonds and modified with substance P (SP) peptide as the targeting ligand. The fabricated SP-HSA-PTX NPs exhibited satisfactory drug-loading content (7.89%) and entrapment efficiency (85.7%) with a spherical structure (about 150 nm) and zeta potential of -12.0 mV. The drug release from SP-HSA-PTX NPs occurred in a redox-responsive manner. Due to the targeting effect of the SP peptide, cellular uptake of SP-HSA-PTX NPs into brain capillary endothelial cells (BCECs) and U87 cells was greatly improved. The low IC, prolonged survival period and the obvious pro-apoptotic effect shown by TUNEL analysis all demonstrated that the fabricated SP-HSA-PTX NPs showed a satisfactory anti-tumor effect and could serve as a novel strategy for GBM treatment.
