Glioma and Microenvironment Dual Targeted Nanocarrier for Improved Antiglioblastoma Efficacy

Overview

Journal Drug Deliv

Specialty Pharmacology

Date 2017 Sep 22

PMID 28933201

Citations 10

Authors

Xiuzhen Wang

Qing Zhang

Lingyan Lv

Junjie Fu

Yan Jiang

Hongliang Xin

Qizheng Yao

Affiliations

Soon will be listed here.

Abstract

Drug delivery systems based on nanoparticles (nano-DDS) have aroused attentions for the treatment of glioblastoma (GBM), the most malignant brain cancer with a dismal prognosis. However, there are still numerous unmet challenges for traditional nano-DDS, such as the poor nanoparticle penetration, short retention in the GBM parenchyma and low glioma targeting ability. Herein, we used Pep-1 and CREKA peptides to construct a novel multifunctional GBM targeting nano-DDS (PC-NP). Pep-1 was used to overcome the blood-brain tumor barrier (BBTB) and home to glioma cells via interleukin-13 receptor-α2-mediated endocytosis, and CREKA was used to bind to fibrin-fibronectin complexes abundantly expressed in tumor microenvironment for enhanced retention in the GBM. Biological studies showed that the cellular uptake of PC-NP by U87MG cells was significantly enhanced compared with the non-targeting NP. Furthermore, CREKA modification increased the binding capacity of PC-NP to fibrin-fibronectin complexes as confirmed by the competition experiment. In accordance with the increased cellular uptake, PC-NP remarkably increased the cytotoxicity of its payload paclitaxel (PTX) against U87MG cells with an IC of 0.176 μg/mL. In vivo fluorescence imaging and antiglioma efficacy evaluation further confirmed that PC-NP accumulated effectively and penetrated deeply into GBM tissue. PC-NP-PTX exhibited a median survival time as long as 61 days in intracranial GBM-bearing mice. In conclusion, our findings indicated PC-NP as a promising nano-DDS for GBM targeting delivery of anticancer drugs.

Citing Articles

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References

Abe K, Shoji M, Chen J, Bierhaus A, Danave I, Micko C . Regulation of vascular endothelial growth factor production and angiogenesis by the cytoplasmic tail of tissue factor. Proc Natl Acad Sci U S A. 1999; 96(15):8663-8. PMC: 17573. DOI: 10.1073/pnas.96.15.8663. View

Chung E, Cheng Y, Morshed R, Nord K, Han Y, Wegscheid M . Fibrin-binding, peptide amphiphile micelles for targeting glioblastoma. Biomaterials. 2013; 35(4):1249-56. PMC: 3880134. DOI: 10.1016/j.biomaterials.2013.10.064. View

Pandya H, Gibo D, Garg S, Kridel S, Debinski W . An interleukin 13 receptor α 2-specific peptide homes to human Glioblastoma multiforme xenografts. Neuro Oncol. 2011; 14(1):6-18. PMC: 3245989. DOI: 10.1093/neuonc/nor141. View

Debinski W, Gibo D, Hulet S, Connor J, Gillespie G . Receptor for interleukin 13 is a marker and therapeutic target for human high-grade gliomas. Clin Cancer Res. 1999; 5(5):985-90. View

Zhang Y, Zhai M, Chen Z, Han X, Yu F, Li Z . Dual-modified liposome codelivery of doxorubicin and vincristine improve targeting and therapeutic efficacy of glioma. Drug Deliv. 2017; 24(1):1045-1055. PMC: 8240983. DOI: 10.1080/10717544.2017.1344334. View

Jiang Y, Wang X, Liu X, Lv W, Zhang H, Zhang M . Enhanced Antiglioma Efficacy of Ultrahigh Loading Capacity Paclitaxel Prodrug Conjugate Self-Assembled Targeted Nanoparticles. ACS Appl Mater Interfaces. 2016; 9(1):211-217. DOI: 10.1021/acsami.6b13805. View

Bianco J, Bastiancich C, Jankovski A, des Rieux A, Preat V, Danhier F . On glioblastoma and the search for a cure: where do we stand?. Cell Mol Life Sci. 2017; 74(13):2451-2466. PMC: 11107640. DOI: 10.1007/s00018-017-2483-3. View

Brown C, Starr R, Aguilar B, Shami A, Martinez C, DApuzzo M . Stem-like tumor-initiating cells isolated from IL13Rα2 expressing gliomas are targeted and killed by IL13-zetakine-redirected T Cells. Clin Cancer Res. 2012; 18(8):2199-209. PMC: 3578382. DOI: 10.1158/1078-0432.CCR-11-1669. View

Ye F, Wu X, Jeong E, Jia Z, Yang T, Parker D . A peptide targeted contrast agent specific to fibrin-fibronectin complexes for cancer molecular imaging with MRI. Bioconjug Chem. 2008; 19(12):2300-3. PMC: 2651601. DOI: 10.1021/bc800211r. View

10.

Ostrom Q, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J . CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. Neuro Oncol. 2014; 16 Suppl 4:iv1-63. PMC: 4193675. DOI: 10.1093/neuonc/nou223. View

11.

Wang B, Lv L, Wang Z, Zhao Y, Wu L, Fang X . Nanoparticles functionalized with Pep-1 as potential glioma targeting delivery system via interleukin 13 receptor α2-mediated endocytosis. Biomaterials. 2014; 35(22):5897-907. DOI: 10.1016/j.biomaterials.2014.03.068. View

12.

Chen C, Duan Z, Yuan Y, Li R, Pang L, Liang J . Peptide-22 and Cyclic RGD Functionalized Liposomes for Glioma Targeting Drug Delivery Overcoming BBB and BBTB. ACS Appl Mater Interfaces. 2017; 9(7):5864-5873. DOI: 10.1021/acsami.6b15831. View

13.

Zhao J, Zhang B, Shen S, Chen J, Zhang Q, Jiang X . CREKA peptide-conjugated dendrimer nanoparticles for glioblastoma multiforme delivery. J Colloid Interface Sci. 2015; 450:396-403. DOI: 10.1016/j.jcis.2015.03.019. View

14.

Colombo M, Giverso C, Faggiano E, Boffano C, Acerbi F, Ciarletta P . Towards the Personalized Treatment of Glioblastoma: Integrating Patient-Specific Clinical Data in a Continuous Mechanical Model. PLoS One. 2015; 10(7):e0132887. PMC: 4505854. DOI: 10.1371/journal.pone.0132887. View

15.

Perez-Herrero E, Fernandez-Medarde A . Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. Eur J Pharm Biopharm. 2015; 93:52-79. DOI: 10.1016/j.ejpb.2015.03.018. View

16.

Simberg D, Duza T, Park J, Essler M, Pilch J, Zhang L . Biomimetic amplification of nanoparticle homing to tumors. Proc Natl Acad Sci U S A. 2007; 104(3):932-6. PMC: 1783417. DOI: 10.1073/pnas.0610298104. View

17.

Fuller G, Scheithauer B . The 2007 Revised World Health Organization (WHO) Classification of Tumours of the Central Nervous System: newly codified entities. Brain Pathol. 2007; 17(3):304-7. PMC: 8095523. DOI: 10.1111/j.1750-3639.2007.00084.x. View

18.

Zhou Z, Qutaish M, Han Z, Schur R, Liu Y, Wilson D . MRI detection of breast cancer micrometastases with a fibronectin-targeting contrast agent. Nat Commun. 2015; 6:7984. PMC: 4557274. DOI: 10.1038/ncomms8984. View

19.

Sehedic D, Cikankowitz A, Hindre F, Davodeau F, Garcion E . Nanomedicine to overcome radioresistance in glioblastoma stem-like cells and surviving clones. Trends Pharmacol Sci. 2015; 36(4):236-52. DOI: 10.1016/j.tips.2015.02.002. View

20.

Kim S, Rait A, Kim E, Pirollo K, Chang E . A tumor-targeting p53 nanodelivery system limits chemoresistance to temozolomide prolonging survival in a mouse model of glioblastoma multiforme. Nanomedicine. 2014; 11(2):301-11. PMC: 4330129. DOI: 10.1016/j.nano.2014.09.005. View