← Back to Search
Improved Anti-glioblastoma Efficacy By IL-13Rα2 Mediated Copolymer Nanoparticles Loaded With Paclitaxel
B. Wang, L. Lv, Z. Wang, Y. Jiang, Wei Lv, X. Liu, Zhongyuan Wang, Yue Zhao, Hongliang Xin, Qunwei Xu
Published 2015 · Chemistry, Medicine
Download PDFAnalyze on Scholarcy
Glioma presents one of the most malignant brain tumors, and the therapeutic effect is often limited due to the existence of brain tumor barrier. Based on interleukin-13 receptor α2 (IL-13Rα2) over-expression on glioma cell, it was demonstrated to be a potential receptor for glioma targeting. In this study, Pep-1-conjugated PEGylated nanoparticles loaded with paclitaxel (Pep-NP-PTX) were developed as a targeting drug delivery system for glioma treatment. The Pep-NP-PTX presented satisfactory size of 95.78 nm with narrow size distribution. Compared with NP-PTX, Pep-NP-PTX exhibited significantly enhanced cellular uptake in C6 cells (p < 0.001). The in vitro anti-proliferation evaluation showed that the IC50 were 146 ng/ml and 349 ng/ml of Pep-NP-PTX and NP-PTX, respectively. The in vivo fluorescent image results indicated that Pep-NP had higher specificity and efficiency in intracranial tumor accumulation. Following intravenous administration, Pep-NP-PTX could enhance the distribution of PTX in vivo glioma section, 1.98, 1.91 and 1.53-fold over that of NP-PTX group after 0.5, 1 and 4 h, respectively. Pep-NP-PTX could improve the anti-glioma efficacy with a median survival time of 32 days, which was significantly longer than that of PTX-NP (23 days) and Taxol® (22 days). In conclusion, Pep-NP-PTX is a potential targeting drug delivery system for glioma treatment.
This paper references
Interleukin‐13 receptor as a unique target for anti‐glioblastoma therapy
S. R. Husain (2001)
A Review of the
Robert Wolpert (1985)
Scientific RepoRts | 5:16589 | DOI: 10
Modern methods for delivery of drugs across the blood-brain barrier.
Y. Chen (2012)
Novel anti–brain tumor cytotoxins specific for cancer cells
W. Debinski (1998)
BBB-Genomics: creating new openings for brain-drug targeting.
W. Pardridge (2001)
Progress on new vaccine strategies for the immunotherapy and prevention of cancer.
J. Berzofsky (2004)
Invasion as target for therapy of glioblastoma multiforme.
Anne Vehlow (2013)
An interleukin 13 receptor α 2-specific peptide homes to human Glioblastoma multiforme xenografts.
Hetal Pandya (2012)
The interleukin-13 receptor alpha2 chain: an essential component for binding and internalization but not for interleukin-13-induced signal transduction through the STAT6 pathway.
K. Kawakami (2001)
A Phase II study of paclitaxel in patients with recurrent malignant glioma using different doses depending upon the concomitant use of anticonvulsants
S. Chang (2001)
Folic acid-Pluronic F127 magnetic nanoparticle clusters for combined targeting, diagnosis, and therapy applications.
Jia-Jyun Lin (2009)
Phase I study of paclitaxel in patients with recurrent malignant glioma: a North American Brain Tumor Consortium report.
S. Chang (1998)
Interleukin-13 fusion cytotoxin as a potent targeted agent for AIDS-Kaposi's sarcoma xenograft.
S. R. Husain (2000)
Current data and strategy in glioblastoma multiforme
G. Iacob (2009)
Glioma therapy using tumor homing and penetrating peptide-functionalized PEG-PLA nanoparticles loaded with paclitaxel.
Q. Hu (2013)
Tight Junctions of the Blood–Brain Barrier
U. Kniesel (2004)
Efficacy of interleukin-13 receptor–targeted liposomal doxorubicin in the intracranial brain tumor model
A. B. Madhankumar (2009)
Uptake of ANG1005, A Novel Paclitaxel Derivative, Through the Blood-Brain Barrier into Brain and Experimental Brain Metastases of Breast Cancer
F. Thomas (2009)
The Authors Declare No Competing Financial Interests. 2 Significance Statement
Odorranalectin-conjugated nanoparticles: preparation, brain delivery and pharmacodynamic study on Parkinson's disease following intranasal administration.
Ziyi Wen (2011)
LyP-1-conjugated PEGylated liposomes: a carrier system for targeted therapy of lymphatic metastatic tumor.
Zhiqiang Yan (2012)
PEGylated poly(trimethylene carbonate) nanoparticles loaded with paclitaxel for the treatment of advanced glioma: in vitro and in vivo evaluation.
Xinyi Jiang (2011)
IL-13Ralpha2 is a glioma-restricted receptor for interleukin-13.
A. Mintz (2002)
Passive and active drug targeting: drug delivery to tumors as an example.
V. Torchilin (2010)
Molecular physiology and pathophysiology of tight junctions in the blood–brain barrier
J. Huber (2001)
Tight junctions and the regulation of gene expression.
M. Balda (2009)
Current status of local therapy in malignant gliomas--a clinical review of three selected approaches.
T. Juratli (2013)
IL-13Rα2 is a Glioma-Restricted Receptor for Interleukin-13
A. Mintz (2002)
Decreasing expression of the interleukin-13 receptor IL-13Ralpha2 in treated recurrent malignant gliomas.
O. Bozinov (2010)
Understanding tubulin–Taxol interactions: Mutations that impart Taxol binding to yeast tubulin
M. Gupta (2003)
Nanoparticles functionalized with Pep-1 as potential glioma targeting delivery system via interleukin 13 receptor α2-mediated endocytosis.
B. Wang (2014)
Convection-enhanced Delivery of Interleukin-13 Receptor-directed Cytotoxin for Malignant Glioma Therapy*
M. Kioi (2006)
Angiopep-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) nanoparticles as dual-targeting drug delivery system for brain glioma.
Hongliang Xin (2011)
Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review.
H. Maeda (2000)
William Pardridge discusses the lack of BBB research
R. N. Lawrence (2002)
Follicle-stimulating hormone peptide can facilitate paclitaxel nanoparticles to target ovarian carcinoma in vivo.
X. Zhang (2009)
Pharmacokinetics and antitumor activity of a bivalent disulfide-stabilized Fv immunotoxin with improved antigen binding to erbB2.
T. Bera (1999)
Polyethylene glycol–polylactic acid nanoparticles modified with cysteine–arginine–glutamic acid–lysine–alanine fibrin-homing peptide for glioblastoma therapy by enhanced retention effect
J. Wu (2014)
RGD and interleukin-13 peptide functionalized nanoparticles for enhanced glioblastoma cells and neovasculature dual targeting delivery and elevated tumor penetration.
Huile Gao (2014)
Pharmacokinetics and biodistribution of nanoparticles.
Shyh-Dar Li (2008)
wrote the main manuscript text. Z.W. and Y.Z. prepared figures and tables. All authors reviewed the manuscript
Current developments in cancer vaccines and cellular immunotherapy.
A. Ribas (2003)
Antitumour activity of ANG1005, a conjugate between paclitaxel and the new brain delivery vector Angiopep‐2
A. Régina (2008)
Phase II study of paclitaxel in patients with recurrent malignant glioma.
M. Prados (1996)
This paper is referenced by
Nanotherapeutics Engineered to Cross the Blood-Brain Barrier for Advanced Drug Delivery to the Central Nervous System.
J. Kim (2019)
The Investigation of the Uptake of Interleukin-13 Conjugated Nanoparticles into Glioma Cells
Michael J. Porter (2016)
Pep-1 peptide-functionalized liposome to enhance the anticancer efficacy of cilengitide in glioma treatment.
Zhuomin Jiao (2017)
Differential Expression Profile of NLRs and AIM2 in Glioma and Implications for NLRP12 in Glioblastoma
N. Sharma (2019)
Therapeutic nanoplatforms and delivery strategies for neurological disorders
Y. Kang (2018)
IL13RA2 is differentially regulated in Papillary Thyroid Carcinoma versus Follicular Thyroid Carcinoma.
S. T. Chong (2019)
Tumortropic adipose‐derived stem cells carrying smart nanotherapeutics for targeted delivery and dual‐modality therapy of orthotopic glioblastoma
Wen-Chia Huang (2017)
Tumor Microenvironment and Angiogenic Blood Vessels Dual-Targeting for Enhanced Anti-Glioma Therapy.
Q. Hu (2016)
Crossing the Blood–Brain Barrier: Recent Advances in Drug Delivery to the Brain
M. Patel (2017)
Managing CNS Tumors: The Nanomedicine Approach
J. Aparicio-Blanco (2017)
Targeting experimental orthotopic glioblastoma with chitosan-based superparamagnetic iron oxide nanoparticles (CS-DX-SPIONs)
M. Shevtsov (2018)
Tumor targeting peptides: novel therapeutic strategies in glioblastoma.
D. Raucher (2019)
Polymeric Nanocarriers Delivering Anticancer Agents for the Treatment of Chemoresistant Prostate Cancer and Lung Metastatic Melanoma
Ruinan Yang (2018)
Nanomaterial-based blood-brain-barrier (BBB) crossing strategies.
Jinbing Xie (2019)
Repositioning Microtubule Stabilizing Drugs for Brain Disorders
Artemis Varidaki (2018)
Thermo-responsive mesoporous silica/lipid bilayer hybrid nanoparticles for doxorubicin on-demand delivery and reduced premature release.
Q. Zhang (2017)
Enhanced Antiglioblastoma Efficacy of Neovasculature and Glioma Cells Dual Targeted Nanoparticles.
L. Lv (2016)
Biomarkers and Immunotherapeutic Targets in Glioblastoma.
A. Hung (2017)
Targeted Theranostic Nanoparticles for Brain Tumor Treatment
M. Mendes (2018)
Magnetic targeting of paclitaxel-loaded poly(lactic-co-glycolic acid)-based nanoparticles for the treatment of glioblastoma
Lakshmi Pallavi Ganipineni (2018)
Paclitaxel-loaded multifunctional nanoparticles for the targeted treatment of glioblastoma
Lakshmi Pallavi Ganipineni (2019)
Glioblastoma multiforme: a glance at advanced therapies based on nanotechnology
V. Rezaei (2020)
PEGylated Polyamidoamine dendrimer conjugated with tumor homing peptide as a potential targeted delivery system for glioma.
Y. Jiang (2016)
Targeted Delivery to Tumors: Multidirectional Strategies to Improve Treatment Efficiency
Olga M. Kutova (2019)
Drug Delivery to the Brain across the Blood-Brain Barrier Using Nanomaterials.
Yung-Hao Tsou (2017)
Targeted and theranostic applications for nanotechnologies in medicine
Saini Setua (2017)
Immunotherapy for gliomas: shedding light on progress in preclinical and clinical development
M. B. Garcia-Fabiani (2020)
Enhanced Antiglioma Efficacy of Ultrahigh Loading Capacity Paclitaxel Prodrug Conjugate Self-Assembled Targeted Nanoparticles.
Y. Jiang (2017)
Development of bioactive materials for glioblastoma therapy
J. Yang (2016)
Current Advances of Tubulin Inhibitors in Nanoparticle Drug Delivery and Vascular Disruption/Angiogenesis
Souvik Banerjee (2016)
A window into the brain: Tools to assess pre-clinical efficacy of biomaterials-based therapies on central nervous system disorders.
J. Samal (2019)
Peptide‐based targeted therapeutics: Focus on cancer treatment
Fatemeh Araste (2018)See more