Enhanced Glioma Targeting and Penetration by Dual-Targeting Liposome Co-modified with T7 and TAT

Zong, Taili; Mei, Ling; Gao, Huile; Shi, Kai; Chen, Jiantao; Wang, Yan; Zhang, Qianyu; Yang, Yuting; He, Qin

doi:10.1002/jps.24186

Cited by 71 publications

(42 citation statements)

References 50 publications

(85 reference statements)

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“…The in vivo targeting effect of liposomes was evidenced by in vivo imaging and ex vivo tumor section ( Figure 9). Recently, many multifunctional delivery systems have been designed for co-delivery of different guests, including micelles (Lee et al, 2009), liposomes (Zong et al, 2014b) and inorganic nanoparticles (Chen et al, 2009). Synergistic combination of two or more drugs was a promising strategy to overcome undesirable toxicity and other side effects by reducing dosage of each agent or accessing context-specific multiple targets (Chen et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Targeted delivery of transferrin and TAT co-modified liposomes encapsulating both paclitaxel and doxorubicin for melanoma

et al. 2015

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The purpose of this study was to develop an efficient dual-ligand based liposomal drug delivery system with targeting specificity as well as properties that would kill melanoma cells. Liposomes modified with transferrin (Tf) and cell-penetrating peptide TAT was prepared, which encapsulated two kinds of chemotherapy drugs, paclitaxel and doxorubicin (Tf/TAT-PTX/DOX-LP). The Tf ligands specifically bind to the overexpressed Tf receptors on the surface of melanoma cells, while the TAT ligands functioned as a classical cell penetrating peptide, helping dual-ligand liposomes be internalized by melanoma cells. The effect of dual-targeting system and ''double-drug'' combination therapy were evaluated both in vitro and in vivo. In vitro, cellular uptake, intracellular distribution and tumor spheroids penetration studies demonstrated that the system could not only be selectively and efficiently penetrate melanoma cells. Besides, apoptosis staining assay and cytotoxicity showed effective anti-tumor capability and obvious synergistic effect of combination therapy of PTX and DOX. In vivo imaging and fluorescent images of tumor section further demonstrated that Tf/TAT-PTX/DOX-LP had the highest tumor distribution. The results of these experiments demonstrated that double-drug liposomal drug delivery systems (DDS) had both enhanced targeting efficiency and increased therapeutic efficacy.

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Section: Discussionmentioning

confidence: 99%

Targeted delivery of transferrin and TAT co-modified liposomes encapsulating both paclitaxel and doxorubicin for melanoma

et al. 2015

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“…6,7 Numerous studies have reported attempts to overcome the BBB. 8 Intranasal administration has been used to circumvent the BBB and deliver drugs to the brain through the olfactory neuroepithelium via the trigeminal and olfactory nerve pathways noninvasively. 9,10 Furthermore, nose-to-brain drug delivery has been performed because of its advantages, including reduced drug delivery to nontarget sites, avoidance of hepatic first-pass metabolism, and convenience, for drugs such as rasagiline, alginate, tarenflurbil, and piperine.…”

Section: Introductionmentioning

confidence: 99%

Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects

Yan¹,

Xu²,

Bi³

et al. 2018

IJN

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Introduction Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson’s disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD. Materials and methods The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs. Results Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference ( P <0.05) in contralateral rotations between rats treated with Lf-R-NPs and those treated with R-NPs. Furthermore, Lf-R-NPs significantly alleviated nigrostriatal dopaminergic neurodegeneration in the rat model of 6-hydroxydopamine-induced PD. Conclusion Our findings show that Lf-R-NPs deliver rotigotine more efficiently to the brain, thereby enhancing efficacy. Therefore, Lf-R-NPs might have therapeutic potential for the treatment of PD.

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“…227 More recently, researchers have developed liposomes that can penetrate the BBB and targeting brain-cancer cells. This new system, known as dual-targeting liposomes, was produced to deliver DOX, 211,213,238 DNR, 250 epirubicin, 249 topotecan, 251 plasmids, 236 and siRNA, 212 and for codelivery of synergistic two-drug combinations. 203,210 All of these dual-targeting liposomes proved to be effective in crossing the BBB and targeting glioma cells.…”

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Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

Vieira

Gamarra

2016

IJN

324

238

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This review summarizes articles that have been reported in literature on liposome-based strategies for effective drug delivery across the blood–brain barrier. Due to their unique physicochemical characteristics, liposomes have been widely investigated for their application in drug delivery and in vivo bioimaging for the treatment and/or diagnosis of neurological diseases, such as Alzheimer’s, Parkinson’s, stroke, and glioma. Several strategies have been used to deliver drug and/or imaging agents to the brain. Covalent ligation of such macromolecules as peptides, antibodies, and RNA aptamers is an effective method for receptor-targeting liposomes, which allows their blood–brain barrier penetration and/or the delivery of their therapeutic molecule specifically to the disease site. Additionally, methods have been employed for the development of liposomes that can respond to external stimuli. It can be concluded that the development of liposomes for brain delivery is still in its infancy, although these systems have the potential to revolutionize the ways in which medicine is administered.

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Enhanced Glioma Targeting and Penetration by Dual-Targeting Liposome Co-modified with T7 and TAT

Cited by 71 publications

References 50 publications

Targeted delivery of transferrin and TAT co-modified liposomes encapsulating both paclitaxel and doxorubicin for melanoma

Targeted delivery of transferrin and TAT co-modified liposomes encapsulating both paclitaxel and doxorubicin for melanoma

Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

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Enhanced Glioma Targeting and Penetration by Dual-Targeting Liposome Co-modified with T7 and TAT

Cited by 71 publications

References 50 publications

Targeted delivery of transferrin and TAT co-modified liposomes encapsulating both paclitaxel and doxorubicin for melanoma

Targeted delivery of transferrin and TAT co-modified liposomes encapsulating both paclitaxel and doxorubicin for melanoma

Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects

Getting into the brain: liposome-based strategies for effective drug delivery across the blood&ndash;brain barrier

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Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier