Pharmacokinetics and antitumor efficacy of DSPE-PEG2000 polymeric liposomes loaded with quercetin and temozolomide: Analysis of their effectiveness in enhancing the chemosensitization of drug-resistant glioma cells

Hu, Jun; Wang, Junjie; Wang, Gang; Yao, Zhongjun; Dang, Xiaoqian

doi:10.3892/ijmm.2016.2458

Cited by 61 publications

(43 citation statements)

References 51 publications

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“…The majority of studies assessing the penetration and efficacy of therapeutic nanoparticles in pre-clinical glioma models utilize relatively large liposomes that largely rely on passive BBB delivery via the enhanced permiability and retention effect [30,31,42,43]. The data presented in this study strongly suggest that O 6 BTG-C18-loaded liposomes require LIFU application to efficiently bypass the BBB and exert potent chemosensitizing effects.…”

Section: Lifu-mediated Delivery Of Lp-o 6 Btg-c18 Reduces Tumor Growtmentioning

confidence: 80%

Chemotherapy sensitization of glioblastoma by focused ultrasound-mediated delivery of therapeutic liposomes

Papachristodoulou

Signorell

Werner

et al. 2019

Journal of Controlled Release

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In glioblastoma, the benefit from temozolomide chemotherapy is largely limited to a subgroup of patients (30-35%) with tumors exhibiting methylation of the promoter region of the O 6-methylguanine-DNA methyltransferase (MGMT) gene. In order to allow more patients to benefit from this treatment, we explored magnetic resonance image-guided microbubble-enhanced low-intensity pulsed focused ultrasound (LIFU) to transiently open the blood-brain barrier and deliver a first-in-class liposome-loaded small molecule MGMT inactivator in mice bearing temozolomide-resistant gliomas. We demonstrate that a liposomal O 6-(4-bromothenyl)guanine (O 6 BTG) derivative can efficiently target MGMT, thereby sensitizing murine and human glioma cells to temozolomide in vitro. Furthermore, we report that image-guided LIFU mediates the delivery of the stable liposomal MGMT inactivator in the tumor region resulting in potent MGMT depletion in vivo. Treatment with this new liposomal MGMT inactivator facilitated by LIFU-mediated blood-brain barrier opening reduced tumor growth and significantly prolonged survival of glioma-bearing mice, when combined with temozolomide chemotherapy. Exploring this novel combined approach in the clinic to treat glioblastoma patients with MGMT promoter-unmethylated tumors is warranted.

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Section: Lifu-mediated Delivery Of Lp-o 6 Btg-c18 Reduces Tumor Growtmentioning

confidence: 80%

Chemotherapy sensitization of glioblastoma by focused ultrasound-mediated delivery of therapeutic liposomes

Papachristodoulou

Signorell

Werner

et al. 2019

Journal of Controlled Release

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“…To date, numerous studies have used liposomes as nanocarriers for combined antitumor drug therapy using active constituents of plants and chemotherapeutic agents. Hu et al [27] developed a liposome using distearoylsn-glycero-3-phosphoethanolamine-N-(methoxy(polyethylene glycol)-2000) (DSPE-PEG 2000), which cocarried temozolomide (TMZ) and quercetin (QUE) for the treatment of drug-resistant U87 glioma cells. Transmission electron microscopy demonstrated that nanoliposomes loaded with TMZ and QUE had reduced diameters.…”

Section: Liposomementioning

confidence: 99%

“…is results in lower drug distribution into the actual tumor, reduced e cacy, and hence an incomplete elimination and subsequent recurrence [27,106]. Several studies have demonstrated that nanodrugs with smaller diameters have increased e cacy because they can penetrate easier and deeper into tumor tissues [33,51].…”

Section: Tumor Accumulation and Penetrationmentioning

confidence: 99%

The Application of Nanotechnology in the Codelivery of Active Constituents of Plants and Chemotherapeutics for Overcoming Physiological Barriers during Antitumor Treatment

Xiong

et al. 2019

BioMed Research International

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Antitumor therapy using a combination of drugs has shown increased clinical efficacy. Active constituents derived from plants can offer several advantages, such as high efficiacy, low toxicity, extensive effects, and multiple targets. At present, the combination of plants’ active constituents and chemotherapeutic drugs has attracted increased attention. Nanodrug delivery systems (NDDSs) have been widely used in tumor-targeted therapy because of their efficacy of delivering antitumor drugs. The in vivo process of tumor-targeted NDDSs has several steps. They include blood circulation, tumor accumulation and penetration, target cell internalization and uptake, and drug release and drug response. In each step, NDDSs encounter multiple barriers that prevent their effective delivery to target sites. Studies have been performed to find alternative strategies to overcome these barriers. We reviewed the recent progress of codelivery of active constituents of plants and chemotherapeutics using NDDSs. Progress into transversing the physiological barriers for more effective in vivo antitumor delivery will be discussed in this review.

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“…For example, a study analyzed liposomes loaded with quercetin and temozolomide to enhance the chemosensitization of drug-resistant cancer cells. The study demonstrated that DSPE-PEG2000 polymeric liposomes were an effective nanocarrier for enhancing drug delivery to tumors (131). …”

Section: Combination Therapies and Deliverymentioning

confidence: 99%

Quercetin as an Emerging Anti-Melanoma Agent: A Four-Focus Area Therapeutic Development Strategy

et al. 2016

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Replacing current refractory treatments for melanoma with new prevention and therapeutic approaches is crucial in order to successfully treat this aggressive cancer form. Melanoma develops from neural crest cells, which express tyrosinase – a key enzyme in the pigmentation pathway. The tyrosinase enzyme is highly active in melanoma cells and metabolizes polyphenolic compounds; tyrosinase expression thus makes feasible a target for polyphenol-based therapies. For example, quercetin (3,3′,4′,5,7-pentahydroxyflavone) is a highly ubiquitous and well-classified dietary polyphenol found in various fruits, vegetables, and other plant products including onions, broccoli, kale, oranges, blueberries, apples, and tea. Quercetin has demonstrated antiproliferative and proapoptotic activity in various cancer cell types. Quercetin is readily metabolized by tyrosinase into various compounds that promote anticancer activity; additionally, given that tyrosinase expression increases during tumorigenesis, and its activity is associated with pigmentation changes in both early- and late-stage melanocytic lesions, it suggests that quercetin can be used to target melanoma. In this review, we explore the potential of quercetin as an anti-melanoma agent utilizing and extrapolating on evidence from previous in vitro studies in various human malignant cell lines and propose a “four-focus area strategy” to develop quercetin as a targeted anti-melanoma compound for use as either a preventative or therapeutic agent. The four areas of focus include utilizing quercetin to (i) modulate cellular bioreduction potential and associated signaling cascades, (ii) affect transcription of relevant genes, (iii) regulate epigenetic processes, and (iv) develop effective combination therapies and delivery modalities/protocols. In general, quercetin could be used to exploit tyrosinase activity to prevent, and/or treat, melanoma with minimal additional side effects.

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Pharmacokinetics and antitumor efficacy of DSPE-PEG2000 polymeric liposomes loaded with quercetin and temozolomide: Analysis of their effectiveness in enhancing the chemosensitization of drug-resistant glioma cells

Cited by 61 publications

References 51 publications

Chemotherapy sensitization of glioblastoma by focused ultrasound-mediated delivery of therapeutic liposomes

Chemotherapy sensitization of glioblastoma by focused ultrasound-mediated delivery of therapeutic liposomes

The Application of Nanotechnology in the Codelivery of Active Constituents of Plants and Chemotherapeutics for Overcoming Physiological Barriers during Antitumor Treatment

Quercetin as an Emerging Anti-Melanoma Agent: A Four-Focus Area Therapeutic Development Strategy

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