- 标题
- 摘要
- 关键词
- 实验方案
- 产品
-
Modulation of Intracellular Oxygen Pressure by Dual-Drug Nanoparticles to Enhance Photodynamic Therapy
摘要： Oxygen plays an essential role in the photodynamic therapy (PDT) of cancer. However, hypoxia inside tumors severely attenuates the therapeutic effect of PDT. To address this issue, a novel strategy is reported for cutting off the oxygen consumption pathway by using sub-50 nm dual-drug nanoparticles (NPs) to attenuate the hypoxia-induced resistance to PDT and to enhance PDT efficiency. Specifically, dual-drug NPs that encapsulate photosensitizer (PS) verteporfin (VER) and oxygen-regulator atovaquone (ATO) with sub-50 nm diameters can penetrate deep into the interior regions of tumors and effectively deliver dual-drug into tumor tissues. Then, ATO released from NPs efficiently reduce in advance cellular oxygen consumption by inhibition of mitochondria respiratory chain and further heighten VER to generate greater amounts of 1O2 in hypoxic tumor. As a result, accompanied with the upregulated oxygen content in tumor cells and laser irradiation, the dual-drug NPs exhibit powerful and overall antitumor PDT effects both in vitro and in vivo, and even tumor elimination. This study presents a potential appealing clinical strategy in photodynamic eradication of tumors.
关键词： atovaquone,verteporfin,hypoxia,oxygen consumption rate,photodynamic therapy
更新于2025-09-19 17:15:36
-
Targeted and synergic glioblastoma treatment: multifunctional nanoparticles delivering verteporfin as adjuvant therapy for temozolomide chemotherapy
摘要： Despite advances in cancer therapies, glioblastoma multiforme treatment remains inefficient due to the brain-blood barrier (BBB) inhibitory activity and to the low Temozolomide (TMZ) chemotherapeutic selectivity. To improve therapeutic outcomes, in this work we propose two strategies: (i) photodynamic therapy (PDT) as adjuvant treatment and (ii) engineering of multifunctional theranostic/targeted nanoparticles (m-NPs) that integrate biotin as a targeting moiety with rhodamine-B as a theranostic agent in Pluronic P85/F127 copolymers. These smart m-NPs can surmount the BBB and co-encapsulate multiple cargoes under optimized conditions. Overall, the present study conducts a rational m-NP design, characterization, and optimizes the formulation conditions. Confocal microscopy studies on T98-G, U87-MG, and U343 glioblastoma cells and on NIH-3T3 normal fibroblast cells show that the m-NPs and the encapsulated drugs are selectively taken up by tumor cells presenting a broad intracellular distribution. The formulations display no toxicity in the absence of light and are not toxic to healthy cells, but they exert a robust synergic action in cancer cells in the case of concomitant PDT/TMZ treatment, especially at low TMZ concentrations and higher light doses, as demonstrated by nonlinear dose–effect curves based on Chou-Talalay method. The results evidenced different mechanisms of action related to the disjoint cell cycle phases at the optimal PDT/TMZ ratio. This effect favors synergism between the PDT and the chemotherapy with TMZ, enhances the antiproliferative effect, and overcomes cross-resistance mechanisms. These results point out that m-NP-based PDT adjuvant therapy is a promising strategy to improve TMZ-based glioblastoma multiforme treatments.
关键词： Verteporfin,Temozolomide,Photodynamic therapy,Nanotechnology,Theranostic
更新于2025-09-19 17:15:36
-
The Efficiency of Verteporfin as a Therapeutic Option in Pre-Clinical Models of Melanoma
摘要： Yes Associated Protein 1 (YAP) and Transcriptional coactivator with PDZ-Binding Motif (TAZ) have gained notoriety for their ability to drive tumor initiation and progression in a wide variety of cancers, including melanoma. YAP and TAZ act as drivers of melanoma through its interaction with the TEAD family of transcription factors. Verteporfin is a benzoporphyrin derivative that is used clinically for photodynamic treatment of macular degeneration. Recently it has emerged as a potential inhibitor of YAP/TAZ-TEAD interaction independent of light activation. In this study we determine if verteporfin has clinical potential by testing this compound on human melanoma cell cultures and in a clinically significant mouse model, BrafCA; Tyr-CreERT2; Ptenf/f, which parallels human melanoma in terms of disease progression, genetics, and histopathology. In culture, Verteporfin treatment induces a rapid drop in YAP and TAZ protein levels and cell numbers. In the transgenic model, utilizing drug levels that correspond to previously determined safe doses in human patients and with a dosing regimen calculated in this study, Verteporfin did not inhibit melanoma initiation or progression in comparison to mock treated controls. Taken together, our study suggests that although Verteporfin induces YAP/TAZ degradation in melanoma cell lines, Verteporfin was not effective as a YAP/TAZ-TEAD specific inhibitor of melanoma in our studies that aimed to mimic conditions found in clinic in terms of treatment regimen and disease model.
关键词： TAZ,Verteporfin,hippo pathway,mouse models,melanoma,YAP
更新于2025-09-19 17:15:36