Qin Xiang, Zhang Hongyue, Wang Zhiqiang, Jin Yingxue
Key Laboratory of Photochemistry Biomaterials and Energy Storage Materials of Heilongjiang Province, Harbin Normal University Harbin 150025 China
RSC Adv. 2018 Mar 14;8(19):10376-10388. doi: 10.1039/c8ra00747k. eCollection 2018 Mar 13.
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 FeO 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 = 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 ( = 62.9%) when compared with free HNPa. In addition, the 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.
光动力疗法（PDT）在临床实践中越来越被认为是治疗各种癌症的替代方法。大多数第二代光敏剂（PS）具有疏水性且靶向选择性差，这限制了它们在光动力疗法中的疗效。本文采用一锅溶剂热法制备了氧化石墨烯（GO）与磁性FeO纳米颗粒和壳聚糖（CS）偶联的材料（MCGO），并将其用作纳米载体来负载我们小组首次合成的新型光敏剂HNPa（λ = 698 nm）。由于其在698 nm（近红外区域）有强吸收，HNPa被认为是一种良好的水溶性药物和出色的组织穿透剂。合成的复合材料（MCGO-HNPa）表现出高稳定性、良好的水溶性和生物相容性、预期的磁靶向性以及即使在低浓度下对光动力疗法也具有良好的光稳定性。我们的研究表明，与游离的HNPa相比，MCGO纳米材料可促进单线态氧的产生和释放（ = 62.9%）。此外，细胞摄取实验表明，MCGO纳米材料可加速HNPa药物进入肿瘤细胞核，且药物释放行为对pH敏感。针对人肝癌细胞系HepG-2的MTT试验结果清楚地表明，MCGO-HNPa复合材料在光照下可有效导致细胞损伤和凋亡性细胞死亡，并且该纳米复合材料可提高PS剂的光动力疗法抗肿瘤效果，且暗毒性可忽略不计。同时，对光反应机制的研究表明，在该光动力疗法过程中I型和II型光动力反应可同时发生，它们的相对贡献取决于光敏剂的类型和剂量。II型对光动力疗法的影响比I型更大，尤其是对于较高剂量的HNPa光敏剂。所有结果揭示了所提出的新策略具有广阔的应用前景。
