Light-Emitting Photon-Upconversion Nanoparticles in the Generation of Transdermal Reactive-Oxygen Species,ACS Applied Materials & Interfaces

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Light-Emitting Photon-Upconversion Nanoparticles in the Generation of Transdermal Reactive-Oxygen Species
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2017-11-21 00:00:00 , DOI: 10.1021/acsami.7b14812
Martin Prieto _{1,

2} , Alina Y. Rwei _{3,

4} , Teresa Alejo _{1,

2} , Tuo Wei ₃ , Maria Teresa Lopez-Franco _{1,

2} , Gracia Mendoza _{1,

2} , Victor Sebastian _{1,

2,

5} , Daniel S. Kohane ₃ , Manuel Arruebo _{1,

2,

5}

Affiliation

Common photosensitizers used in photodynamic therapy do not penetrate the skin effectively. In addition, the visible blue and red lights used to excite such photosensitizers have shallow penetration depths through tissue. To overcome these limitations, we have synthesized ultraviolet- and visible-light-emitting, energy-transfer-based upconversion nanoparticles and coencapsulated them inside PLGA–PEG (methoxy poly(ethylene glycol)-b-poly(lactic-co-glycolic acid)) nanoparticles with the photosensitizer protoporphyrin IX. Nd³⁺ has been introduced as a sensitizer in the upconversion nanostructure to allow its excitation at 808 nm. The subcytotoxic doses of the hybrid nanoparticles have been evaluated on different cell lines (i.e., fibroblasts, HaCaT, THP-1 monocytic cell line, U251MG (glioblastoma cell line), and mMSCs (murine mesenchymal stem cells). Upon NIR (near infrared)-light excitation, the upconversion nanoparticles emitted UV and VIS light, which consequently activated the generation of reactive-oxygen species (ROS). In addition, after irradiating at 808 nm, the resulting hybrid nanoparticles containing both upconversion nanoparticles and protoporphyrin IX generated 3.4 times more ROS than PLGA–PEG nanoparticles containing just the same dose of protoporphyrin IX. Their photodynamic effect was also assayed on different cell cultures, demonstrating their efficacy in selectively killing treated and irradiated cells. Compared to the topical application of the free photosensitizer, enhanced skin permeation and penetration were observed for the nanoparticulate formulation, using an ex vivo human-skin-permeation experiment. Whereas free protoporphyrin IX remained located at the outer layer of the skin, nanoparticle-encapsulated protoporphyrin IX was able to penetrate through the epidermal layer slightly into the dermis.

中文翻译：

发光的光子上转换纳米粒子在透皮活性氧物种的产生中。

在光动力疗法中使用的普通光敏剂不能有效地渗透皮肤。另外，用于激发这种光敏剂的可见的蓝色和红色光具有穿过组织的浅穿透深度。为了克服这些限制，我们合成了基于紫外线和可见光的，基于能量转移的上转换纳米粒子，并将它们共封装在PLGA-PEG（甲氧基聚（乙二醇）-b-聚（乳酸-共-乙醇酸））中）含有光敏剂原卟啉IX的纳米颗粒。钕³⁺已在上转换纳米结构中将其作为敏化剂引入，以使其在808 nm处激发。已经在不同的细胞系（即成纤维细胞，HaCaT，THP-1单核细胞系，U251MG（胶质母细胞瘤细胞系）和mMSC（鼠间充质干细胞））上评估了杂合纳米颗粒的亚细胞毒性剂量。激发下，上转换纳米粒子发出UV和VIS光，从而激活了活性氧（ROS）的生成；此外，在808 nm照射后，含有上转换纳米粒子和原卟啉IX的杂化纳米粒子产生了3.4倍的光。与仅含相同剂量原卟啉IX的PLGA-PEG纳米颗粒相比，ROS数量更多。还可以在不同的细胞培养物中测定其光动力效应，证明了它们在选择性杀死经处理和辐照的细胞方面的功效。与游离光敏剂的局部施用相比，使用离体人皮肤渗透实验观察到纳米颗粒制剂的皮肤渗透和渗透增强。游离的原卟啉IX保留在皮肤的外层，而纳米颗粒包封的原卟啉IX能够略微穿透表皮层进入真皮。

更新日期：2017-11-21

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