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含石墨烯和 5-氟尿嘧啶的药物制剂,用于基于发光二极管的皮肤癌光化学疗法。

Pharmaceutical Formulations Containing Graphene and 5-Fluorouracil for Light-Emitting Diode-Based Photochemotherapy of Skin Cancer.

机构信息

LEPABE─Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-180 Porto, Portugal.

ALiCE─Associate Laboratory in Chemical Engineering, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-180 Porto, Portugal.

出版信息

ACS Appl Mater Interfaces. 2024 Jan 31;16(4):4333-4347. doi: 10.1021/acsami.3c13409. Epub 2024 Jan 19.

Abstract

Nonmelanoma skin cancer (NMSC) is the most common cancer worldwide, among which 80% is basal cell carcinoma (BCC). Current therapies' low efficacy, side effects, and high recurrence highlight the need for alternative treatments. In this work, a partially reduced nanographene oxide (p-rGOn) developed in our laboratory was used. It has been achieved through a controlled reduction of nanographene oxide via UV-C irradiation that yields small nanometric particles (below 200 nm) that preserve the original water stability while acquiring high light-to-heat conversion efficiency. The latter is explained by a loss of carbon-oxygen single bonds (C-O) and the re-establishment of sp carbon bonds. p-rGOn was incorporated into a Carbopol hydrogel together with the anticancer drug 5-fluorouracil (5-FU) to evaluate a possible combined PTT and chemotherapeutic effect. Carbopol/p-rGOn/5-FU hydrogels were considered noncytotoxic toward normal skin cells (HFF-1). However, when A-431 skin cancer cells were exposed to NIR irradiation for 30 min in the presence of Carbopol/p-rGOn/5-FU hydrogels, almost complete eradication was achieved after 72 h, with a 90% reduction in cell number and 80% cell death of the remaining cells after a single treatment. NIR irradiation was performed with a light-emitting diode (LED) system, developed in our laboratory, which allows adjustment of applied light doses to achieve a safe and selective treatment, instead of the standard laser systems that are associated with damages in the healthy tissues in the tumor surroundings. Those are the first graphene-based materials containing pharmaceutical formulations developed for BCC phototherapy.

摘要

非黑色素瘤皮肤癌(NMSC)是全球最常见的癌症,其中 80%为基底细胞癌(BCC)。目前疗法的疗效低、副作用大、复发率高,这突显了对替代疗法的需求。在这项工作中,我们实验室开发了一种部分还原的纳米氧化石墨烯(p-rGOn)。它是通过 UV-C 照射对纳米氧化石墨烯进行受控还原而得到的,生成了小的纳米级颗粒(小于 200nm),同时保留了原始的水分稳定性,同时获得了高光-热转换效率。这可以通过碳-氧单键(C-O)的损失和 sp 碳键的重建来解释。p-rGOn 与抗癌药物 5-氟尿嘧啶(5-FU)一起被掺入 Carbopol 水凝胶中,以评估可能的联合 PTT 和化疗效果。Carbopol/p-rGOn/5-FU 水凝胶被认为对正常皮肤细胞(HFF-1)没有细胞毒性。然而,当 A-431 皮肤癌细胞在 Carbopol/p-rGOn/5-FU 水凝胶存在的情况下,用近红外光照射 30 分钟时,经过 72 小时后几乎完全被清除,经过一次处理后,细胞数量减少了 90%,剩余细胞的死亡率达到了 80%。近红外光照射是使用我们实验室开发的发光二极管(LED)系统进行的,该系统可以调整施加的光剂量,以实现安全和选择性的治疗,而不是使用与肿瘤周围健康组织损伤相关的标准激光系统。这些是第一个开发用于 BCC 光疗的含有药物制剂的基于石墨烯的材料。

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