As nanomedicine-based clinical strategies have continued to develop, the possibility of combining chemotherapy and singlet oxygen-dependent photodynamic therapy (PDT) to treat pancreatic cancer (PaC) has emerged as a viable therapeutic modality. The efficacy of such an approach, however, is likely to be constrained by the mechanisms of drug release and tumor oxygen levels. In the present study, we developed an Fe(III)-complexed porous coordination network (PCN) which we then used to encapsulate PTX (PCN-Fe(III)-PTX) nanoparticles (NPs) in order to treat PaC via a combination of chemotherapy and PDT. The resultant NPs were able to release drug in response to both laser irradiation and pH changes to promote drug accumulation within tumors. Furthermore, through a Fe(III)-based Fenton-like reaction these NPs were able to convert H₂O₂ in the tumor site to O₂, thereby regulating local hypoxic conditions and enhancing the efficacy of PDT approaches. Also these NPs were suitable for use as a T₁-MRI weighted contrast agent, making them viable for monitoring therapeutic efficacy upon treatment. Our results in both cell line and animal models of PaC suggest that these NPs represent an ideal agent for mediating effective MRI-guided chemotherapy-PDT, giving them great promise for the clinical treatment of PaC.

中文翻译：

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PCN-Fe（III）-PTX纳米粒子通过减轻肿瘤缺氧用于MRI指导的胰腺癌高效化学光动力疗法

随着基于纳米药物的临床策略的不断发展，将化学疗法与单线态氧依赖性光动力疗法（PDT）结合用于治疗胰腺癌（PaC）的可能性已成为一种可行的治疗方法。然而，这种方法的功效可能受到药物释放和肿瘤氧水平的机制的限制。在本研究中，我们开发了一种Fe（III）复合的多孔配位网络（PCN），然后将其用于封装PTX（PCN-Fe（III）-PTX）纳米粒子（NPs），以便通过以下方法组合治疗PaC：化疗和PDT。产生的NP能够响应激光照射和pH变化释放药物，以促进药物在肿瘤内的积累。此外，通过基于Fe（III）的Fenton样反应，这些NP能够转化H在肿瘤部位将₂ O ₂变为O ₂，从而调节局部低氧状况并增强PDT方法的功效。这些NP也适合用作T ₁ -MRI加权的造影剂，使其对于监测治疗后的疗效是可行的。我们在PaC的细胞系和动物模型中的结果都表明，这些NPs是介导有效的MRI指导的化学疗法PDT的理想药物，为它们在PaC的临床治疗中提供了广阔的前景。