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用于癌症诊疗的无载体纳米颗粒,具有双模态磁共振成像/荧光成像以及光热与化学动力学联合治疗功能。

Carrier-free nanoparticles for cancer theranostics with dual-mode magnetic resonance imaging/fluorescence imaging and combination photothermal and chemodynamic therapy.

作者信息

Ding Yuhan, Deng Caiting, Yang Yuchen, Zhang Jingjing, Liu Wen, Aras Omer, An Feifei, Liu Jun, Chai Yichao

机构信息

The Comprehensive Breast Care Center, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157 Xiwu Road, Xi'an, Shaanxi 710004, China; School of Public Health, Health Science Center, Xi'an Jiaotong University, No.76 Yanta West Road, Xi'an, Shaanxi 710061, China.

School of Public Health, Health Science Center, Xi'an Jiaotong University, No.76 Yanta West Road, Xi'an, Shaanxi 710061, China; Institute of Medical Engineering, School of Basic Medical Science, Health Science Center, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi 710061 China.

出版信息

Int J Pharm. 2025 Feb 25;671:125285. doi: 10.1016/j.ijpharm.2025.125285. Epub 2025 Jan 27.

Abstract

Both photothermal therapy (PTT) and chemodynamic therapy (CDT) are designed to focus their antitumor effect on only the tumor site, thereby minimizing unwanted severe damage to healthy tissue outside the tumor. However, each monotherapy is limited in achieving complete tumor eradication, resulting in tumor recurrence. The combination of multiple therapies may help to overcome the limitations of single therapy, improve the chances of complete tumor eradication, and reduce the risk of recurrence. Here, we report a novel multifunctional carrier-free nanoparticle, namely Mn-TPP@ICG, prepared through the self-assembly of ICG and 5,10,15,20-Tetraphenyl-21H,23H-porphine manganese (III) chloride (Mn-TPP). The prepared Mn-TPP@ICG allowed dual-mode imaging in the form of magnetic resonance imaging (MRI) and near-infrared (NIR) fluorescence imaging, as well as combination therapy in the form of CDT and PTT. In vitro experiments revealed that Mn-TPP@ICG nanoparticles can enable CDT by converting intratumoral hydrogen peroxide (HO) to highly cytotoxic hydroxyl radicals (·OH) and PTT through photothermal conversion, resulting in a strong synergistic antitumor effect. Furthermore, in vivo experiments revealed that CDT and PTT with Mn-TPP@ICG nanoparticles effected a synergistically enhanced therapeutic effect in 4T1 tumor-bearing mice, significantly inhibiting tumor growth compared with monomodal treatments with no treatment, only CDT, or only PTT. Lastly, imaging experiments unveiled the exceptional capability of Mn-TPP@ICG nanoparticles in enabling fluorescence imaging and high-resolution MRI upon their intravenous administration. Thus, a meaningful carrier-free nanoparticle strategy for the synergistic combination of CDT and PTT was provided in our study, broadening the applications of nanotheranostics.

摘要

光热疗法(PTT)和化学动力疗法(CDT)均旨在将其抗肿瘤作用仅聚焦于肿瘤部位,从而最大程度减少对肿瘤外健康组织的不必要严重损伤。然而,每种单一疗法在实现完全根除肿瘤方面都存在局限性,导致肿瘤复发。多种疗法的联合可能有助于克服单一疗法的局限性,提高完全根除肿瘤的几率,并降低复发风险。在此,我们报告了一种新型的无载体多功能纳米颗粒,即通过吲哚菁绿(ICG)与5,10,15,20-四苯基-21H,23H-卟啉氯化锰(III)(Mn-TPP)自组装制备的Mn-TPP@ICG。所制备的Mn-TPP@ICG能够以磁共振成像(MRI)和近红外(NIR)荧光成像的形式进行双模态成像,以及以CDT和PTT的形式进行联合治疗。体外实验表明,Mn-TPP@ICG纳米颗粒可通过将肿瘤内过氧化氢(HO)转化为高细胞毒性的羟基自由基(·OH)实现CDT,并通过光热转换实现PTT,从而产生强大的协同抗肿瘤作用。此外,体内实验表明,使用Mn-TPP@ICG纳米颗粒进行CDT和PTT在4T1荷瘤小鼠中产生了协同增强的治疗效果,与未治疗、仅进行CDT或仅进行PTT的单模态治疗相比,显著抑制了肿瘤生长。最后,成像实验揭示了Mn-TPP@ICG纳米颗粒在静脉注射后进行荧光成像和高分辨率MRI的卓越能力。因此,我们的研究提供了一种有意义的无载体纳米颗粒策略,用于CDT和PTT的协同联合,拓宽了纳米诊疗学的应用范围。

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