Asn-Gly-Arg-modified polydopamine-coated nanoparticles for dual-targeting therapy of brain glioma in rats

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Abstract

The blood-brain barrier (BBB) is the major clinical obstacle in the chemotherapeutic management of brain glioma. Here we synthesized a pH-sensitive dual-targeting doxorubicin (DOX) carrier to compromise tumor endothelial cells, enhance BBB transportation, and improve drug accumulation in glioma cells. The drug delivery system was constructed with polydopamine (PDA)-coated mesoporous silica nanoparticles (NPs, MSNs) and the PDA coating was functionalized with Asn-Gly-Arg (NGR), a ligand with specific affinity for cluster of differentiation 13 (CD13). MSN-DOX-PDA-NGR showed a higher intracellular accumulation in primary brain capillary endothelial cells (BCECs) and C6 cells and greater BBB permeability than the non-targeting NPs (MSN-DOX-PDA) did in vitro. Ex vivo and in vivo tests showed that MSN-DOX-PDA-NGR had a higher accumulation in intracranial tumorous tissue than the undecorated NPs did. Furthermore, the antiangiogenesis and antitumor efficacy of MSN-DOX-PDA-NGR were stronger than that of MSN-DOX-PDA. Therefore, these results indicate that the dual-targeting vehicles are potentially useful in brain glioma therapy.

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Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery.

Fangqiong Tang, Linlin Li, Dong Chen (2012)

In the past decade, mesoporous silica nanoparticles (MSNs) have attracted more and more attention for their potential biomedical applications. With their tailored mesoporous structure and high surface area, MSNs as drug delivery systems (DDSs) show significant advantages over traditional drug nanocarriers. In this review, we overview the recent progress in the synthesis of MSNs for drug delivery applications. First, we provide an overview of synthesis strategies for fabricating ordered MSNs and hollow/rattle-type MSNs. Then, the in vitro and in vivo biocompatibility and biotranslocation of MSNs are discussed in relation to their chemophysical properties including particle size, surface properties, shape, and structure. The review also highlights the significant achievements in drug delivery using mesoporous silica nanoparticles and their multifunctional counterparts as drug carriers. In particular, the biological barriers for nano-based targeted cancer therapy and MSN-based targeting strategies are discussed. We conclude with our personal perspectives on the directions in which future work in this field might be focused. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Biocompatibility, biodistribution, and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals.

Jie Lu, Monty Liong, Zongxi Li … (2010)

Mesoporous silica nanoparticles (MSNs) are a promising material for drug delivery. In this Full Paper, MSNs are first shown to be well tolerated, as demonstrated by serological, hematological, and histopathological examinations of blood samples and mouse tissues after MSN injection. Biodistribution studies using human cancer xenografts are carried out with in vivo imaging and fluorescent microscopy imaging, as well as with inductively coupled plasma mass spectroscopy. The results show that MSNs preferentially accumulate in tumors. Finally, the drug-delivery capability of MSNs is demonstrated by following tumor growth in mice treated with camptothecin-loaded MSNs. These results indicate that MSNs are biocompatible, preferentially accumulate in tumors, and effectively deliver drugs to the tumors and suppress tumor growth.

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Acid pH in tumors and its potential for therapeutic exploitation.

I Tannock, D. Rotin (1989)

Measurement of pH in tissue has shown that the microenvironment in tumors is generally more acidic than in normal tissues. Major mechanisms which lead to tumor acidity probably include the production of lactic acid and hydrolysis of ATP in hypoxic regions of tumors. Further reduction in pH may be achieved in some tumors by administration of glucose (+/- insulin) and by drugs such as hydralazine which modify the relative blood flow to tumors and normal tissues. Cells have evolved mechanisms for regulating their intracellular pH. The amiloride-sensitive Na+/H+ antiport and the DIDS-sensitive Na+-dependent HCO3-/Cl- exchanger appear to be the major mechanisms for regulating pHi under conditions of acid loading, although additional mechanisms may contribute to acid extrusion. Mitogen-induced initiation of proliferation in some cells is preceded by cytoplasmic alkalinization, usually triggered by stimulation of Na+/H+ exchange; proliferation of other cells can be induced without prior alkalinization. Mutant cells which lack Na+/H+ exchange activity have reduced or absent ability to generate solid tumors; a plausible explanation is the failure of such mutant cells to withstand acidic conditions that are generated during tumor growth. Studies in tissue culture have demonstrated that the combination of hypoxia and acid pHe is toxic to mammalian cells, whereas short exposures to either factor alone are not very toxic. This interaction may contribute to cell death and necrosis in solid tumors. Acidic pH may influence the outcome of tumor therapy. There are rather small effects of pHe on the response of cells to ionizing radiation but acute exposure to acid pHe causes a marked increase in response to hyperthermia; this effect is decreased in cells that are adapted to low pHe. Acidity may have varying effects on the response of cells to conventional anticancer drugs. Ionophores such as nigericin or CCCP cause acid loading of cells in culture and are toxic only at low pHc; this toxicity is enhanced by agents such as amiloride or DIDS which impair mechanisms involved in regulation of pHi. It is suggested that acid conditions in tumors might allow the development of new and relatively specific types of therapy which are directed against mechanisms which regulate pHi under acid conditions.

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Journal

Journal ID (nlm-ta): Oncotarget

Journal ID (iso-abbrev): Oncotarget

Journal ID (publisher-id): Oncotarget

Journal ID (publisher-id): ImpactJ

Title: Oncotarget

Publisher: Impact Journals LLC

ISSN (Electronic): 1949-2553

Publication date Collection: 8 November 2016

Publication date (Electronic): 15 September 2016

Volume: 7

Issue: 45

Pages: 73681-73696

Affiliations

¹ Department of Neurosurgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

² Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging of Chongqing Medical University, Chongqing, 400016, China

³ College of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China

⁴ Department of Orthopaedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

Author notes

Correspondence to: Huzhi Zheng, zhenghz@ 123456swu.edu.cn

Yuan Cheng, chengyuan023@ 123456aliyun.com

Article

Publisher ID: 12047

DOI: 10.18632/oncotarget.12047

PMC ID: 5342007

PubMed ID: 27655664

SO-VID: 943ccb11-540e-43e2-87bd-90e07d3bba99

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Asn-Gly-Arg-modified polydopamine-coated nanoparticles for dual-targeting therapy of brain glioma in rats

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Abstract

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Nanoparticles to cross the blood-brain barrier (BBB)

Most cited references 36

Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery.

Biocompatibility, biodistribution, and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals.

Acid pH in tumors and its potential for therapeutic exploitation.

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