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Magnetic chitosan/graphene oxide composite loaded with novel photosensitizer for enhanced photodynamic therapy

机译：磁性壳聚糖/氧化石墨烯复合材料负载新型光敏剂以增强光动力治疗

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Photodynamic therapy (PDT) is an increasingly recognized alternative to treat various cancers in clinical practice. Most second-generation photosensitizers (PS) are hydrophobic and have poor targeting selectivity, which limit their efficacy for PDT. In this paper, graphene oxide (GO) coupled with magnetic Fe _(3) O _(4) nanoparticles and chitosan (CS) (MCGO) was prepared by a one-pot solvothermal method and used as a nanocarrier for loading the new photosensitizer HNPa (λ _(max) = 698 nm), which was first synthesized by our group, and was considered as a good water-soluble drug and an excellent tissue-penetrating agent due to its strong absorption at 698 nm (near-infrared region). The synthesized composite (MCGO–HNPa) showed high stability, good water solubility and biocompatibility, expected magnetic targetability, and good photostability for PDT even in low concentrations. Our research reveals that MCGO nanomaterials can promote the production and release of singlet oxygen ( Φ _(Δ) = 62.9%) when compared with free HNPa. In addition, the in vitro cell uptake experiments suggested that the MCGO nanomaterials can accelerate the penetration of HNPa drugs into the tumor cell nucleus and that the drug release behavior is pH-sensitive. The MTT assay results against human hepatoma cell lines HepG-2 clearly show that the MCGO–HNPa composite can effectively result in cell damage and apoptotic cell death under light, and that the nanocomposite can improve the PDT antitumor effect of PS agents with negligible dark toxicity. Meanwhile, the research on the photoreaction mechanism reveals that Type I and Type II photodynamic reactions can occur simultaneously in this PDT process, and their relative contributions depend on the type and dose of the photosensitizer. Type II has a greater effect on PDT than Type I, especially for a higher HNPa photosensitizer dose. All the results reveal the promising application of the presented novel strategy.
机译：在临床实践中，光动力疗法（PDT）是治疗各种癌症的公认替代方法。大多数第二代光敏剂（PS）都是疏水性的，且靶向选择性差，这限制了它们对PDT的功效。本文采用一锅溶剂热法制备了氧化石墨烯（GO）以及磁性Fe _（3）O _（4）纳米粒子和壳聚糖（CS）（MCGO），并将其用作负载新型光敏剂的纳米载体。 HNPa（λ_（max）= 698 nm），是我们小组首先合成的，由于在698 nm（近红外区）的强吸收而被认为是一种良好的水溶性药物和一种优良的组织穿透剂。 ）。合成的复合材料（MCGO–HNPa）即使在低浓度下也显示出高稳定性，良好的水溶性和生物相容性，预期的磁性靶向性以及对PDT的良好的光稳定性。我们的研究表明，与游离HNPa相比，MCGO纳米材料可以促进单线态氧的产生和释放（Φ_（Δ）= 62.9％）。此外，体外细胞摄取实验表明，MCGO纳米材料可以促进HNPa药物渗透到肿瘤细胞核中，并且药物释放行为对pH敏感。 MTT对人肝癌细胞HepG-2的检测结果清楚地表明，MCGO-HNPa复合物在光照下可有效导致细胞损伤和凋亡，而纳米复合材料可改善PS试剂的PDT抗肿瘤作用，而暗毒性可忽略不计。同时，对光反应机理的研究表明，在这种PDT过程中，I型和II型光动力反应可以同时发生，它们的相对贡献取决于光敏剂的类型和剂量。 II型对PDT的影响大于I型，特别是对于HNPa光敏剂剂量较高的情况。所有结果揭示了提出的新颖策略的有希望的应用。

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