Anti-glioblastoma efficacy and safety of paclitaxel-loading Angiopep-conjugated dual targeting PEG-PCL nanoparticles.
Therapeutic effect of glioma is often limited due to low permeability of delivery systems across the Blood-Brain Barrier (BBB) and poor penetration into the tumor tissue. In order to overcome the two barriers, we proposed Angiopep-conjugated PEG-PCL nanoparticles (ANG-PEG-NP) as a dual targeting drug delivery system for glioma treatment basing on low density lipoprotein receptor related protein (LRP) receptor not only over-expressed on BBB but also on glioma cells. This system could transport across BBB through LRP-mediated transcytosis and then targeted glioma via LRP-mediated endocytosis. In this study, we evaluated the preliminary availability and safety of ANG-PEG-NP for glioma treatment. The penetration, distribution, and accumulation into 3D glioma spheroid and in vivo glioma region of ANG-PEG-NP were obviously higher than that of plain PEG-PCL nanoparticles (PEG-NP). The anti-glioblastoma efficacy of paclitaxel (PTX) loading ANG-PEG-NP was significantly enhanced as compared to that of Taxol and PEG-NP. Preliminary safety results showed that no acute toxicity to hematological system, liver, kidney and brain tissue was observed after intravenous administration with a dose of 100 mg/kg blank ANG-PEG-NP per day for a week. Results indicate that Angiopep-conjugated dual targeting PEG-PCL nanoparticle is a potential brain targeting drug delivery system for glioma treatment.
Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai 201203, China.
Hongliang
H
Xin
Xianyi
X
Sha
Xinyi
X
Jiang
Wei
W
Zhang
Liangcen
L
Chen
Xiaoling
X
Fang
D000595:Amino Acid Sequence; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism
C531860:Angiopep-2; D000972:Antineoplastic Agents, Phytogenic; D010455:Peptides; D011092:Polyethylene Glycols; D017239:Paclitaxel