Synergistic Anti-glioma Effects &lt;i&gt;in Vitro&lt;/i&gt; and &lt;i&gt;in Vivo&lt;/i&gt; of Enediyne Antibiotic Neocarzinostatin and Paclitaxel &lt;i&gt;via&lt;/i&gt; Enhanced Growth Delay and Apoptosis-Induction

Tianqin, Gao; Chen, Cheng; Wang, Jingjing

doi:10.1248/bpb.b16-00285

Cited by 14 publications

(7 citation statements)

References 43 publications

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“…1,2 The main treatment of glioma is traditional surgery, but generally glioma cannot be completely removed with high relapse rate, poor prognosis and the median survival length <15 months after surgery. [3][4][5] It has become a serious threat to human health. To restrain and effectively eradicate glioma, chemotherapy becomes the most common choice.…”

Section: Introductionmentioning

confidence: 99%

Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex

Xin¹,

Liu²,

Han³

et al. 2021

IJN

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Background: Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood-brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumorspecific selectivity and penetration. Methods: Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly. Results: The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and −15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6 luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect. Conclusion:Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.

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Section: Introductionmentioning

confidence: 99%

Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex

Xin¹,

Liu²,

Han³

et al. 2021

IJN

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“…Glioblastoma multiforme (GBM) is the most fatal central nervous system malignancy with a median survival of only 12–18 months in adults,1 and of which the 5‐year survival is even less than 5% 2. Despite advances in medicine, the protective BBB hampers the entry of essentially 100% of large‐molecular drugs/imaging probes and over 98% of small‐molecular drugs/imaging probes into brain,3 resulting in poor chemotherapy and diagnosis.…”

Section: Introductionmentioning

confidence: 99%

“…Glioblastoma multiforme (GBM) is the most fatal central nervous system malignancy with a median survival of only 12-18 months in adults, [1] and of which the 5-year survival is even less than 5%. [2] Despite advances in medicine, the protective BBB hampers the entry of essentially 100% of large-molecular drugs/imaging probes and over 98% of Noteworthily, the emerging nanoparticulate systems based on adsorption-mediated transcytosis (AMT) [6] or receptormediated transcytosis (RMT) [7] pathways seem to be a viable strategy to transport therapeutic and imaging agents into brain. Thereinto, coupling the drug-carrier with a targeting ligand to recognize specific receptor on brain capillary endothelial cells (BCECs), i.e., RMT-based drug delivery, is mostly adopted in recent years.…”

Section: Introductionmentioning

confidence: 99%

Molecular Probe Crossing Blood–Brain Barrier for Bimodal Imaging–Guided Photothermal/Photodynamic Therapies of Intracranial Glioblastoma

Xiao

Cai

et al. 2020

Adv Funct Materials

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Currently, treatment of intracranial diseases still remains a great challenge because the blood–brain barrier (BBB) blocks access of most drugs to the central nervous system. Herein, a theranostic small molecular probe, iRGD‐ICG‐Lys‐DTPA@Gd (iRGD‐ILD), capable of crossing BBB is developed. Owing to the small molecular size and αvβ3 integrin receptor–mediated transcytosis, this tailor‐made molecular probe integrating the fluorescence and magnetic resonance imaging functions effectively passes through BBB to target tumor cells even in the early stage of glioblastoma multiforme (GBM), thereby allowing a bimodal imaging–guided therapy of GBM. The reactive oxygen species and heat generated by the ICG moiety under the 808 nm laser irradiation exert photodynamic/photothermal therapeutic effects, which results in significantly inhibited tumor growth and prolonged median survival of C6‐Luc glioma‐bearing mice. Notably, the integration of FDA‐approved clinically available agents, e.g., ICG, DTPA and Gd, into a molecular probe may ensure desirable biocompatibility and biosafety for in vivo applications. Overall, the results highlight the potential of a water‐soluble small molecule as a novel theranostic probe for highly effective GBM treatment.

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“…Glioma is the most aggressive primary cancer in the central nervous system, especially in brain (Tianqin et al 2016;Ignarro et al 2017;Sun et al 2016;Chen et al 2016) and constitute approximately 30% of all brain and central nervous system tumors and 80% of all malignant brain tumors (Ma et al 2016). Nowadays, the common clinical treatments of glioblastoma are surgery concomitant with radiotherapy, chemotherapy or combined treatments (Tianqin et al 2016;Wang et al 2013). But these treatments are rarely curative because chemotherapy has limited effects (Yang et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Apoptotic effects of ε-viniferin in combination with cis-platin in C6 cells

et al. 2018

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Glioblastoma (GBM) is one of the most common and lethal forms of primary brain tumors in human adults. Treatment options are limited, and in most cases ineffective. Natural products are sources of novel compounds endowed with therapeutic properties in many human diseases like cancer. ε-viniferin is a resveratrol dimer and well known for having antiproliferative and apoptotic effects on cancer cells. Cisplatin is a platinum containing anti-cancer drug. In this study, we aimed to investigate antiproliferative and apoptotic effects of using cis-platin and ε-viniferin alone or in combined treatment of C6 cells. Cell proliferation was detected by WST-1. Mitochondrial membrane potential changes in the cells (ΔΨm) were evaluated using cationic dye JC1. Apoptotic index which is a hallmark of late apoptosis was detected by using Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method and apoptotic alterations were observed by transmission electron microscope (TEM). Activation of caspase-8, -9, -3 in C6 cells at various incubation periods was measured by flow cytometer. Apoptotic index increased at highest level in only combined treatment cells (91.6%) after 48 h incubation. These results were supported by TEM images. Caspase-8 activation in C6 cells increased to a maximum (12.5%) after 6 h by using combined cis-platin/ε-viniferin treatment (13.25/95 μM). Caspase-9 was activated at 44.5% after combined treatment for 24 h. This rate is higher than using cis-platin (14.2%) or ε-viniferin (43.3%) alone. The combined 13.25 μM/cisplatin and 95 μM ε-viniferin treatment caused maximum caspase-3 activation in C6 cells (15.5%) at the end of the 72 h incubation. In conclusion, it was observed that caspase-8, -9, -3 activation which was determined in vitro, trigerred apoptotic mechanism in C6 cells by using low concentrations of combined cis-platin and ε-viniferin.

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Synergistic Anti-glioma Effects <i>in Vitro</i> and <i>in Vivo</i> of Enediyne Antibiotic Neocarzinostatin and Paclitaxel <i>via</i> Enhanced Growth Delay and Apoptosis-Induction

Cited by 14 publications

References 43 publications

Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex

Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex

Molecular Probe Crossing Blood–Brain Barrier for Bimodal Imaging–Guided Photothermal/Photodynamic Therapies of Intracranial Glioblastoma

Apoptotic effects of ε-viniferin in combination with cis-platin in C6 cells

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