Tumor microenvironment sensitive doxorubicin delivery and release to glioma using angiopep-2 decorated gold nanoparticles

Ruan, Shaobo; Yuan, Mingqing; Zhang, Li; Hu, Guanlian; Chen, Jiantao; Cun, Xingli; Zhang, Qianyu; Yang, Yuting; He, Qin; Gao, Huile

doi:10.1016/j.biomaterials.2014.10.007

Cited by 289 publications

(209 citation statements)

References 49 publications

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“…The reduced size promotes the intratumor penetration of the drug delivery systems, enabling homogenous distribution in the tumor. We decorated R8-RGD onto AuNPsGNPs for brain tumor targeting imaging and doxorubicin delivery (Ruan et al 2015b). The R8-RGD modified AuNPs-GNPs showed higher localization in the brain tumor than the unmodified AuNPs-GNPs.…”

Section: Dual Targeting With One Ligandmentioning

confidence: 99%

Perspectives on Dual Targeting Delivery Systems for Brain Tumors

Gao

2016

J Neuroimmune Pharmacol

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110

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Brain tumor remains one of the most serious threats to human beings. Different from peripheral tumors, drug delivery to brain tumor is largely restricted by the blood brain barrier (BBB). To fully conquer this barrier and specifically deliver drugs to brain tumor, dual targeting delivery systems were explored, which are functionalized with two active targeting ligands: one to the BBB and the other to the brain tumor. The development of dual targeting delivery system is still in its early stage, and attentions need to be paid to issues and concerns that remain unresolved in future studies.

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Section: Dual Targeting With One Ligandmentioning

confidence: 99%

Perspectives on Dual Targeting Delivery Systems for Brain Tumors

Gao

2016

J Neuroimmune Pharmacol

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110

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“…Though DOX has poor targeting efficiency, DOX solution could prolong the median survival time, which is mainly ascribed to its broad-spectrum anticancer activity. 49 DOX + GM1 solution combined the advantages of antitumor effect and neuron repair, resulting in longer median survival time. Because of BBB penetration, the DOX/GM1 group showed prolonged survival among all the treatment groups.…”

Section: Therapeutic Efficacy In Tumor-bearing Ratsmentioning

confidence: 99%

Penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system

Zou

Wang

Lei

et al. 2017

IJN

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For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood–brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design. The in vitro study demonstrated a slow and sustainable drug release in physiological conditions. In the cellular uptake studies, mixed micelles could effectively transport into both human umbilical vein endothelial cells and C6 cells. Furthermore, biodistribution imaging of mice showed that the DiR/GM1 mixed micelles were accumulated sustainably and distributed centrally in the brain. Experiments on zebrafish confirmed that drug-loaded GM1 micelles can overcome the BBB and enter the brain. Among all the treatment groups, the median survival time of C6-bearing rats after administering DOX/GM1 micelles was significantly prolonged. In conclusion, the ganglioside nanomicelles developed in this work can not only penetrate BBB effectively but also repair nerves and kill tumor cells at the same time.

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“…B16 and HepG2 cell lines were tested in vitro to evaluate the radiosensitization activity of AuNPs and the combination treatment strategy. DOX is a broad-spectrum anti-cancer drug and was reported to cure many kinds of cancers, including numerous reports for melanoma and hepatic carcinoma (13,(35)(36)(37). The cellular uptake results presented that Au concentration decreased after reaching the peak concentration, which could be explained by the exocytosis of AuNPs in the later stage (38).…”

Section: Discussionmentioning

confidence: 96%

Thermosensitive Hydrogel Co-loaded with Gold Nanoparticles and Doxorubicin for Effective Chemoradiotherapy

Zhang

Wang

et al. 2015

AAPS J

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Abstract. Chemoradiotherapy, as a well-established paradigm to treat various cancers, still calls for novel strategies. Recently, gold nanoparticles (AuNPs) have been shown to play an important role as a radiosensitizer in cancer radiotherapy. The aim of this study was to evaluate the combination of polyethylene glycol (PEG) modified AuNPs and doxorubicin (DOX) to improve cancer chemoradiotherapy, in which the AuNPs was the radiosensitizer and the DOX was the model chemotherapeutic. A Pluronic® F127-based thermosensitive hydrogel (Au-DOX-Gel) loading AuNPs and DOX was developed by Bcold method^for intratumoral injection. The formulation was optimized at a F127 concentration of 22% for Au-DOX-Gel. The release profiles compared to a control group were assessed in vitro and in vivo. Au-DOX-Gel showed sustained release of AuNPs and DOX. The cell viability and surviving fraction of mouse melanoma (B16) and Human hepatocellular liver carcinoma (HepG2) cells were significantly inhibited by the combination treatment of DOX and AuNPs under radiation. Tumor sizes of mice were significantly decreased by Au-DOX-Gel compared to controls. Interestingly, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Ki-67 staining results showed that tumor cell growth and proliferation were inhibited by AuNPs combined with DOX under radiation, suggesting that the radiosensitization activity and combination effects might be caused by inhibition of tumor cell growth and proliferation. Furthermore, the results of skin safety tests, histological observation of organs, and the body weight changes indicated in vivo safety of Au-DOX-Gel. In conclusion, the Au-DOX-Gel developed in this study could represent a promising strategy for improved cancer chemoradiotherapy.

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Tumor microenvironment sensitive doxorubicin delivery and release to glioma using angiopep-2 decorated gold nanoparticles

Cited by 289 publications

References 49 publications

Perspectives on Dual Targeting Delivery Systems for Brain Tumors

Perspectives on Dual Targeting Delivery Systems for Brain Tumors

Penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system

Thermosensitive Hydrogel Co-loaded with Gold Nanoparticles and Doxorubicin for Effective Chemoradiotherapy

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Tumor microenvironment sensitive doxorubicin delivery and release to glioma using angiopep-2 decorated gold nanoparticles

Cited by 289 publications

References 49 publications

Perspectives on Dual Targeting Delivery Systems for Brain Tumors

Perspectives on Dual Targeting Delivery Systems for Brain Tumors

Penetration of blood&ndash;brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system

Thermosensitive Hydrogel Co-loaded with Gold Nanoparticles and Doxorubicin for Effective Chemoradiotherapy

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Penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system