Blood Brain Barrier: A Challenge for Effectual Therapy of Brain Tumors

Bhowmik, Arijit; Khan, Rajni; Ghosh, Mrinal K.

doi:10.1155/2015/320941

Cited by 230 publications

(171 citation statements)

References 240 publications

(196 reference statements)

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“…In GBM, a disruption of BBB by the primary tumor sites is often observed [35]. This altered BBB allows passive accumulation of chemotherapeutic drugs in the vicinity of the disruption [36]. However, the degree of BBB disruption varies depending on the region of the GBM tumors and may be negligible for certain tumors.…”

Section: Crossing the Bbb: A Challenge For Gbm Therapymentioning

confidence: 99%

Effective treatment of glioblastoma requires crossing the blood–brain barrier and targeting tumors including cancer stem cells: The promise of nanomedicine

Kim

Harford

Pirollo

et al. 2015

Biochemical and Biophysical Research Communications

121

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Glioblastoma multiforme (GBM) is the most aggressive and lethal type of brain tumor. Both therapeutic resistance and restricted permeation of drugs across the blood–brain barrier (BBB) play a major role in the poor prognosis of GBM patients. Accumulated evidence suggests that in many human cancers, including GBM, therapeutic resistance can be attributed to a small fraction of cancer cells known as cancer stem cells (CSCs). CSCs have been shown to have stem cell-like properties that enable them to evade traditional cytotoxic therapies, and so new CSC-directed anti-cancer therapies are needed. Nanoparticles have been designed to selectively deliver payloads to relevant target cells in the body, and there is considerable interest in the use of nanoparticles for CSC-directed anti-cancer therapies. Recent advances in the field of nanomedicine offer new possibilities for overcoming CSC-mediated therapeutic resistance and thus significantly improving management of GBM. In this review, we will examine the current nanomedicine approaches for targeting CSCs and their therapeutic implications. The inhibitory effect of various nanoparticle-based drug delivery system towards CSCs in GBM tumors is the primary focus of this review.

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Section: Crossing the Bbb: A Challenge For Gbm Therapymentioning

confidence: 99%

Effective treatment of glioblastoma requires crossing the blood–brain barrier and targeting tumors including cancer stem cells: The promise of nanomedicine

Kim

Harford

Pirollo

et al. 2015

Biochemical and Biophysical Research Communications

121

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“…The efflux and influx transporters of BBB comprise transporters like ATP-binding cassette transporters and solute carrier transporters. [12] The different types of transport across the BBB are shown in Figure 1 The inability of drugs to cross the BBB is one of the major impairments to developing treatments for neurological diseases. [13][14][15][16] This highly restrictive, physiologic barrier prevents 98% of small-molecule drugs and virtually 100% of large-molecule drugs from reaching the central nervous system from blood circulation.…”

Section: Ideal Properties Of Nanoparticles For Drug Deliverymentioning

confidence: 99%

“…Possible advantages of nanoparticle delivery systems over conventional anticancer chemotherapy include: (i) protection of drugs from degradation in the body; (ii) enhanced absorption into tumor cells; and (iii) decreased interaction of drugs with normal cells. [8] Ideal properties of nanoparticles for drug delivery are shown in Table 1. Nano-based drug delivery carriers, or nanocarriers, can consist of a wide variety of materials, both organic (polymeric, lipid, protein, or viral) and inorganic.…”

Section: Introductionmentioning

confidence: 99%

Nanocarrier drugs in the treatment of brain tumors

Černá¹,

Stiborová²,

Adam³

et al. 2016

JCMT

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Nanoparticle-mediated targeted delivery of drugs might significantly reduce the dosage and optimize their release properties, increase specificity and bioavailability, improve shelf life, and reduce toxicity. Some nanodrugs are able to overcome the blood-brain barrier that is an obstacle to treatment of brain tumors. Vessels in tumors have abnormal architecture and are highly permeable; moreover, tumors also have poor lymphatic drainage, allowing for accumulation of macromolecules greater than approximately 40 kDa within the tumor microenvironment. Nanoparticles exploit this feature, known as the enhanced permeability and retention effect, to target solid tumors. Active targeting, i.e. surface modification of nanoparticles, is a way to decrease uptake in normal tissue and increase accumulation in a tumor, and it usually involves targeting surface membrane proteins that are upregulated in cancer cells. The targeting molecules are typically antibodies or their fragments; aptamers; oligopeptides or small molecules. There are currently several FDA-approved nanomedicines, but none approved for brain tumor therapy. This review, based both on the study of literature and on the authors own experimental work describes a comprehensive overview of preclinical and clinical research of nanodrugs in therapy of brain tumors. This is an open access article distributed under the terms of the Creative Commons AttributionNonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. For reprints contact: service@oaepublish.com ReviewOpen Access

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“…The presence of intact BTB in these regions of tumors considerably impedes drug delivery from the blood to the tumor tissue, leading to a high recurrence rate after chemotherapy. 3 A host of animal studies in recent years have demonstrated that in the presence of circulating microbubbles (MBs), focused ultrasound (FUS) at low acoustic pressures could be used to open the blood-brain barrier (BBB) of normal brains locally, noninvasively and reversibly. [4][5][6][7][8][9] Studies performed on nonhuman primates have revealed that BBB opening could be realized by FUS exposure with MBs through the intact skull.…”

Section: Introductionmentioning

confidence: 99%

Enhanced delivery of paclitaxel liposomes using focused ultrasound with microbubbles for treating nude mice bearing intracranial glioblastoma xenografts

Shen¹,

Pi²,

Yan³

et al. 2017

IJN

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Paclitaxel liposomes (PTX-LIPO) are a clinically promising antineoplastic drug formulation for the treatment of various extracranial cancers, excluding glioblastoma. A main reason for this is the presence of the blood–brain barrier (BBB) or blood–tumor barrier (BTB), preventing liposomal drugs from crossing at a therapeutically meaningful level. Focused ultrasound (FUS) in conjunction with microbubbles (MBs) has been suggested in many studies to be an effective approach to increase the BBB or BTB permeability. In this study, we investigated the feasibility of enhancing the delivery of PTX-LIPO in intracranial glioblastoma-bearing nude mice using pulsed low-intensity FUS exposure in the presence of MBs. Our results showed that the delivery efficiency of PTX-LIPO could be effectively improved in terms of the penetration of both the BBB in vitro and BTB in vivo by pulsed FUS sonication with a 10 ms pulse length and 1 Hz pulse repetition frequency at 0.64 MPa peak-rarefactional pressure in the presence of MBs. Quantitative analysis showed that a 2-fold higher drug concentration had accumulated in the glioblastoma 3 h after FUS treatment, with 7.20±1.18 µg PTX per g glioma tissue. Longitudinal magnetic resonance imaging analysis illustrated that the intracranial glioblastoma progression in nude mice treated with PTX-LIPO delivered via FUS with MBs was suppressed consistently for 4 weeks compared to the untreated group. The medium survival time of these tumor-bearing nude mice was significantly prolonged by 20.8%, compared to the untreated nude mice. Immunohistochemical analysis further confirmed the antiproliferation effect and cell apoptosis induction. Our study demonstrated that noninvasive low-intensity FUS with MBs can be used as an effective approach to deliver PTX-LIPO in order to improve their chemotherapy efficacy toward glioblastoma.

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Blood Brain Barrier: A Challenge for Effectual Therapy of Brain Tumors

Cited by 230 publications

References 240 publications

Effective treatment of glioblastoma requires crossing the blood–brain barrier and targeting tumors including cancer stem cells: The promise of nanomedicine

Effective treatment of glioblastoma requires crossing the blood–brain barrier and targeting tumors including cancer stem cells: The promise of nanomedicine

Nanocarrier drugs in the treatment of brain tumors

Enhanced delivery of paclitaxel liposomes using focused ultrasound with microbubbles for treating nude mice bearing intracranial glioblastoma xenografts

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