Photodynamic therapy (PDT) has garnered immense attention as a minimally invasive clinical treatment modality for malignant cancers. However, its low penetration depth and photodamage of living tissues by UV and visible light, which activate a photosensitizer, limit the application of PDT. In this study, monodisperse NaYF₄:Yb³⁺/Er³⁺ nanospheres 20 nm in diameter, that serve as near‐infrared (NIR)‐to‐visible light converters and activators of a photosensitizer, were synthesized by high‐temperature co‐precipitation of lanthanide chlorides in a high‐boiling organic solvent (octadec‐1‐ene). The nanoparticles were coated with a thin shell (≈3 nm) of homogenous silica via the hydrolysis and condensation of tetramethyl orthosilicate. The NaYF₄:Yb³⁺/Er³⁺@SiO₂ particles were further functionalized by methacrylate‐terminated groups via 3‐(trimethoxysilyl)propyl methacrylate. To introduce a large number of reactive amino groups on the particle surface, methacrylate‐terminated NaYF₄:Yb³⁺/Er³⁺@SiO₂ nanospheres were modified with a branched polyethyleneimine (PEI) via Michael addition. Aluminum carboxyphthalocyanine (Al Pc‐COOH) was then conjugated to NaYF₄:Yb³⁺/Er³⁺@SiO₂‐PEI nanospheres via carbodiimide chemistry. The resulting NaYF₄:Yb³⁺/Er³⁺@SiO₂‐PEI‐Pc particles were finally modified with succinimidyl ester of poly(ethylene glycol) (PEG) in order to alleviate their future uptake by the reticuloendothelial system. Upon 980 nm irradiation, the intensive red emission of NaYF₄:Yb³⁺/Er³⁺@SiO₂‐PEI‐Pc‐PEG nanoparticles completely vanished, indicating efficient energy transfer from the nanoparticles to Al Pc‐COOH, which generates singlet oxygen (¹O₂). Last but not least, NaYF₄:Yb³⁺/Er³⁺@SiO₂‐PEI‐Pc‐PEG nanospheres were intratumorally administered into mammary carcinoma MDA‐MB‐231 growing subcutaneously in athymic nude mice. Extensive necrosis developed at the tumor site of all mice 24–48 h after irradiation by laser at 980 nm wavelength. The results demonstrate that the NaYF₄:Yb³⁺/Er³⁺@SiO₂‐PEI‐Pc‐PEG nanospheres have great potential as a novel NIR‐triggered PDT nanoplatform for deep‐tissue cancer therapy.

中文翻译：

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酞菁共轭上转换NaYF4：Yb3 + / Er3 + @ SiO2纳米球在肿瘤小鼠模型中用于NIR触发的光动力疗法

作为针对恶性肿瘤的微创临床治疗方法，光动力疗法（PDT）已引起了广泛的关注。然而，其低的渗透深度以及对紫外线和可见光的活组织光损伤，从而激活了光敏剂，从而限制了PDT的应用。在这项研究中，通过高温共聚合成了直径为20 nm的单分散NaYF ₄：Yb ³⁺ / Er ³⁺纳米球，用作近红外（NIR）-可见光转换器和光敏剂的活化剂。在高沸点有机溶剂（十八烷基-1-烯）中沉淀镧系元素氯化物。通过原硅酸四甲酯的水解和缩合，纳米颗粒被均匀的二氧化硅薄壳（约3 nm）覆盖。NaYF ₄：Yb ³⁺ / Er ³⁺ @SiO ₂颗粒通过甲基丙烯酸3-（三甲氧基甲硅烷基）丙基酯被甲基丙烯酸酯封端的基团进一步官能化。为了在颗粒表面引入大量反应性氨基，对甲基丙烯酸酯封端的NaYF ₄：Yb ³⁺ / Er ³⁺ @SiO ₂纳米球进行了迈克尔加成，并用支链聚乙烯亚胺（PEI）进行了改性。然后通过碳二亚胺化学将羧基酞菁铝（Al Pc-COOH）与NaYF ₄：Yb ³⁺ / Er ³⁺ @SiO ₂ -PEI纳米球共轭。生成的NaYF ₄：Yb ³⁺ / Er最后用聚（乙二醇）（PEG）的琥珀酰亚胺酯对³⁺ @SiO ₂ -PEI-Pc颗粒进行改性，以减轻其将来被网状内皮系统吸收的可能性。980 nm照射后，NaYF ₄：Yb ³⁺ / Er ³⁺ @SiO ₂ -PEI-Pc-PEG纳米粒子的强烈红色发射完全消失，表明从纳米粒子到Al Pc-COOH的有效能量转移，产生单线态氧（¹ O ₂）。最后但并非最不重要的是NaYF ₄：Yb ³⁺ / Er ³⁺ @SiO ₂在无胸腺裸鼠皮下生长的乳癌MDA-MB-231中，肿瘤内施用了PEI-Pc-PEG纳米球。在980 nm波长的激光照射后24-48 h，所有小鼠的肿瘤部位均出现广泛的坏死。结果表明，NaYF ₄：Yb ³⁺ / Er ³⁺ @SiO ₂ -PEI-Pc-PEG纳米球作为一种新型的由NIR触发的PDT纳米平台，具有用于深层组织癌治疗的巨大潜力。