Photodynamic Therapy for the Treatment of Glioblastoma

Cramer, Samuel W.; Chen, Clark C.

doi:10.3389/fsurg.2019.00081

Cited by 129 publications

(122 citation statements)

References 80 publications

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“…In addition to sensitizing cytotoxic reactions, ALA-induced PpIX produces a strong red fluorescence under relatively low intensity exciting light. Many oncologists, particularly those treating glioblastoma, have exploited this property for fluorescence-guided resection (FGR), i.e., to clearly demarcate tumor extremities before surgical removal, thereby greatly improving procedural accuracy [9,29,30] . Consequently, ALA-induced PpIX has the advantage of serving as a surgical guide on the one hand and a cytotoxic PDT sensitizer on the other hand.…”

Section: Photodynamic Therapy For Glioblastoma and Other Solid Tumorsmentioning

confidence: 99%

“…An early study by Gilissen et al [31] using a rat aorta model showed that PDT impairs NO generation by vascular endothelial cells, suggesting that the anti-tumor effects of PDT might be due to vasoconstriction of the tumor reactive oxygen species-based mechanisms are depicted: Type I (free radical) vs . Type II (singlet oxygen) [9] microvasculature. In another in vitro study, Gupta et al [32] reported that nNOS in epidermoid cancer cells was rapidly upregulated by PDT-like stress and that the resulting NO was cytotoxic, enhancing the effects of PDT per se.…”

Section: Role Of No In Pdt Resistance and Cell Aggressiveness: Backgrmentioning

confidence: 99%

“…A Jablonski diagram and reactive oxygen species-based mechanisms are depicted: Type I (free radical) vs. Type II (singlet oxygen) [ 9 ]…”

Section: Figurementioning

confidence: 99%

“…Drug resistance can either be inherent or acquired during treatment [ 5 , 6 ] . One of the advantages of non-ionizing photodynamic therapy (PDT) is that it can often overcome or circumvent chemo- and radiotherapeutic resistance, yet various forms of treatment-induced resistance also exist for PDT [ 7 – 9 ] . One of these is based on nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS/NOS2) in PDT-challenged tumor cells.…”

Section: Introductionmentioning

confidence: 99%

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Nitric oxide-elicited resistance to anti-glioblastoma photodynamic therapy

Girotti¹,

Fahey²,

Korytowski³

2020

CDR

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Glioblastoma multiforme is a highly aggressive primary brain malignancy that resists most conventional chemoand radiotherapeutic interventions. Nitric oxide (NO), a short lived free radical molecule produced by inducible NO synthase (iNOS) in glioblastomas and other tumors, is known to play a key role in tumor persistence, progression, and chemo/radiotherapy resistance. Site-specific and minimally invasive photodynamic therapy (PDT), based on oxidative damage resulting from non-ionizing photoactivation of a sensitizing agent, is highly effective against glioblastoma, but resistance also exists in this case. Studies in the authors' laboratory have shown that much of the latter is mediated by iNOS/NO. For example, when glioblastoma U87 or U251 cells sensitized in mitochondria with 5-aminolevulinic acid-induced protoporphyrin IX were exposed to a moderate dose of visible light, the observed apoptosis was strongly enhanced by an iNOS activity inhibitor or NO scavenger, indicating that iNOS/NO had increased cell resistance to photokilling. Moreover, cells that survived the photochallenge proliferated, migrated, and invaded more aggressively than controls, and these responses were also driven predominantly by iNOS/NO. Photostress-upregulated iNOS rather than basal enzyme was found to be responsible for all the negative effects described. Recognition of NO-mediated hyper-resistance/hyper-aggression in PDT-stressed glioblastoma has stimulated interest in how these responses can be prevented or at least minimized by pharmacologic adjuvants such as inhibitors of iNOS activity or transcription. Recent developments along these lines and their clinical potential for improving anti-glioblastoma PDT are discussed.

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Section: Photodynamic Therapy For Glioblastoma and Other Solid Tumorsmentioning

confidence: 99%

Section: Role Of No In Pdt Resistance and Cell Aggressiveness: Backgrmentioning

confidence: 99%

“…A Jablonski diagram and reactive oxygen species-based mechanisms are depicted: Type I (free radical) vs. Type II (singlet oxygen) [ 9 ]…”

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nitric oxide-elicited resistance to anti-glioblastoma photodynamic therapy

Girotti¹,

Fahey²,

Korytowski³

2020

CDR

View full text Add to dashboard Cite

show abstract

“…There is a clear and present need for significant improvement in treatments for both newly diagnosed and recurrent GBM. Notably, there have been multiple clinical studies investigating photonics-based PDT and fluorescence guided resection (FGR) to better clean the margins and improve survival 16 – 26 . For these reasons, 5-ALA (a pro-drug) for fluorescence-guided PDT in grade III and IV gliomas has been approved by FDA 18 .…”

Section: Introductionmentioning

confidence: 99%

Sonodynamic therapy in combination with photodynamic therapy shows enhanced long-term cure of brain tumor

Borah

Cacaccio

Durrani

et al. 2020

Sci Rep

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This article presents the construction of a multimodality platform that can be used for efficient destruction of brain tumor by a combination of photodynamic and sonodynamic therapy. For in vivo studies, U87 patient-derived xenograft tumors were implanted subcutaneously in SCID mice. For the first time, it has been shown that the cell-death mechanism by both treatment modalities follows two different pathways. For example, exposing the U87 cells after 24 h incubation with HPPH [3-(1′-hexyloxy)ethyl-3-devinyl-pyropheophorbide-a) by ultrasound participate in an electron-transfer process with the surrounding biological substrates to form radicals and radical ions (Type I reaction); whereas in photodynamic therapy, the tumor destruction is mainly caused by highly reactive singlet oxygen (Type II reaction). The combination of photodynamic therapy and sonodynamic therapy both in vitro and in vivo have shown an improved cell kill/tumor response, that could be attributed to an additive and/or synergetic effect(s). Our results also indicate that the delivery of the HPPH to tumors can further be enhanced by using cationic polyacrylamide nanoparticles as a delivery vehicle. Exposing the nano-formulation with ultrasound also triggered the release of photosensitizer. The combination of photodynamic therapy and sonodynamic therapy strongly affects tumor vasculature as determined by dynamic contrast enhanced imaging using HSA-Gd(III)DTPA.

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Implantable MicroLED‐Mediated Chemo‐Photodynamic Combination Therapy for Glioma Treatment

Kim,

Lee,

Park

et al. 2024

Adv Funct Materials

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Photodynamic therapy shows promise for glioma treatment with powerful efficacy and low resistance, however, its effectiveness is significantly lowered by inadequate light delivery through the skull. Herein, a needle‐type implantable microLED device and cathepsin B‐responsive prodrug nanoparticles (PNPs) are newly exploited for glioma's chemo‐photodynamic combination therapy. The microLED containing four small LEDs on the tip of its guide needle can be implanted into the center of glioma tissues without large area opening of skull, uniformly irradiating light to deep glioma tissues. PNPs are formulated via self‐assembly of heterobifunctional prodrug composed of doxorubicin, verteporfin, and cathepsin B‐cleavable peptide linker, wherein they stably maintain inactive nanoparticle structures in normal physiological conditions and specifically deliver therapeutic age to cathepsin B‐overexpressed glioma tissues. In vitro cellular assays, PNPs irradiated with showed the synergistic cytotoxicity of DOX and VFP only in cathepsin B‐overexpressed cancer cells rather than normal cells. In tumor‐bearing mice, PNPs showed high tumor accumulation via the nanoparticle‐driven enhanced permeation and retention (EPR) effect and they also exhibited remarkable therapeutic efficacy against glioma under microLED‐mediated light irradiation via chemo‐photodynamic combination therapy. Accordingly, applying microLED with PNPs is an outstanding strategy to defeat glioma with cooperative chemo‐photodynamic effects, minimal invasiveness, and desirable systemic/local safety.

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Photodynamic Therapy for the Treatment of Glioblastoma

Cited by 129 publications

References 80 publications

Nitric oxide-elicited resistance to anti-glioblastoma photodynamic therapy

Nitric oxide-elicited resistance to anti-glioblastoma photodynamic therapy

Sonodynamic therapy in combination with photodynamic therapy shows enhanced long-term cure of brain tumor

Implantable MicroLED‐Mediated Chemo‐Photodynamic Combination Therapy for Glioma Treatment

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