Departamento de Química Inorgânica, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, RJ, 24020-150, Brazil.
Núcleo Multidisciplinar de Pesquisa em Biologia (NUMPEX-Bio), Campus UFRJ-Duque de Caxias Prof. Geraldo Cidade, Universidade Federal do Rio de Janeiro, Duque de Caxias, RJ, Brazil.
Colloids Surf B Biointerfaces. 2022 Jan;209(Pt 1):112169. doi: 10.1016/j.colsurfb.2021.112169. Epub 2021 Oct 22.
Two platforms based on reduced graphene oxide (rGO) functionalized with Pluronic® P123 (rGO-P123) and polyethyleneimine - PEI (rGO-PEI) polymers and loaded with amphotericin B (AmB) were fabricated and tested against Leishmania amazonensis, which can cause cutaneous and diffuse cutaneous leishmaniasis. The materials rGO-P123 and rGO-PEI were efficiently loaded with AmB - a polyene antibiotic - which resulted in rGO-P123-AmB (0.078 mg per mg of material) and rGO-PEI-AmB (0.086 mg per mg of material). Under near-infrared (NIR) light irradiation, the amount of AmB released from rGO-PEI-AmB at pH 5.0 and 7.4 doubled in comparison to AmB released in the absence of NIR light under identical conditions. It was accompanied by a photothermal effect. Otherwise, rGO-P123-AmB did not show a significant change in AmB released in the presence and absence of NIR light. Cytotoxicity studies in mammalian host macrophages revealed that rGO-PEI and rGO-PEI-AmB were nontoxic to the host cells, whereas rGO-123 and rGO-P123-AmB were very toxic, particularly the latter. Therefore, only rGO-PEI and rGO-PEI-AmB were tested against L. amazonensis promastigotes in the presence and absence of NIR light. In vitro antiproliferative effects revealed that rGO-PEI-AmB showed a more pronounced activity against the parasite than rGO-PEI, which was improved under NIR light irradiation. Scanning-transmission electron microscopy of L. amazonensis promastigotes after incubation with rGO-PEI or rGO-PEI-AmB suggested autophagic and necrotic cell death. Thus, the facile synthesis, high AmB loading capacity and good photothermal effect make the rGO-PEI-AmB platform a promising candidate for the topical treatment of cutaneous leishmaniasis.
两种基于还原氧化石墨烯(rGO)的平台,分别用 Pluronic® P123(rGO-P123)和聚乙烯亚胺(PEI)(rGO-PEI)聚合物进行功能化,并负载两性霉素 B(AmB),被制备并用于测试对抗引起皮肤和皮肤扩散型利什曼病的利什曼原虫。rGO-P123 和 rGO-PEI 有效地负载了多烯抗生素两性霉素 B,导致 rGO-P123-AmB(每毫克材料 0.078 毫克)和 rGO-PEI-AmB(每毫克材料 0.086 毫克)。在近红外(NIR)光照射下,rGO-PEI-AmB 在 pH 值为 5.0 和 7.4 时释放的 AmB 量是在相同条件下没有 NIR 光照射时释放的 AmB 量的两倍。这伴随着光热效应。否则,rGO-P123-AmB 在有或没有 NIR 光的情况下释放的 AmB 没有明显变化。在哺乳动物宿主巨噬细胞中的细胞毒性研究表明,rGO-PEI 和 rGO-PEI-AmB 对宿主细胞无毒,而 rGO-123 和 rGO-P123-AmB 则非常有毒,尤其是后者。因此,只有 rGO-PEI 和 rGO-PEI-AmB 被用于在有或没有 NIR 光的情况下测试对抗 L. amazonensis 前鞭毛体。体外增殖抑制作用表明,rGO-PEI-AmB 对寄生虫的活性比 rGO-PEI 更强,在 NIR 光照射下效果更好。与 rGO-PEI 或 rGO-PEI-AmB 孵育后的 L. amazonensis 前鞭毛体的扫描透射电子显微镜显示自噬和坏死性细胞死亡。因此,rGO-PEI-AmB 平台具有易于合成、高 AmB 负载能力和良好的光热效应,有望成为治疗皮肤利什曼病的局部治疗方法。
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