PO.CH01.04 · 化学
共包封替莫唑胺的radioPDT纳米颗粒对胶质母细胞瘤的治疗具有有效的细胞毒性
Temozolomide co-encapsulated radioPDT nanoparticles possess effective cytotoxicity for the treatment of glioblastoma
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
引言：放射激活的光动力疗法（radio-PDT）已成为一种有前景的方法，可克服传统光动力疗法的局限，尤其是外部光源组织穿透性差的问题。本研究聚焦于共包封替莫唑胺的radio-PDT纳米颗粒的合成、表征及其对胶质母细胞瘤治疗效果的评估。
材料与方法：合成了一种无机纳米闪烁体，并采用能量色散X射线光谱（EDS）、透射电子显微镜（TEM）和X射线衍射（XRD）对其进行全面的物理化学表征，以评估其组成、尺寸和结构的演变。该纳米闪烁体与光敏剂原卟啉IX（PPIX）联合替莫唑胺（TMZ）一起包封于PEG-PLGA纳米载体中。采用TEM、动态光散射（DLS）评估纳米颗粒的特性，并记录zeta电位。使用U251细胞系体外评估这些纳米颗粒的肿瘤细胞毒性。此外，通过Western blot阐明其分子机制。
结果：我们的结果显示纳米闪烁体的尺寸为15±5，其与PPIX和替莫唑胺一起包封于PEG-PLGA纳米载体中。最终纳米复合物尺寸为100±10，zeta电位（ZP）为-21.5。与对照条件相比，这些纳米颗粒对肿瘤细胞表现出显著的细胞毒性。Western blot分析显示，在radioPDT及低剂量照射下的TMZ共包封radioPDT中，AKT、PERK和BCL2的表达降低，而剪切型caspase 3的表达升高。
结论：我们的结果支持将TMZ共包封radioPDT以及radioPDT联合放疗用作治疗深部肿瘤、特别是放射抵抗性胶质母细胞瘤的一种有效方法。这些纳米颗粒表现出优异的生物相容性、对肿瘤细胞的有效细胞毒性，以及转化为体内肿瘤研究的潜力。
查看英文原文 English abstract
Introduction: Radiation-activated photodynamic therapy (radio-PDT) has emerged as a promising approach to overcome the limitations of conventional photodynamic therapy, particularly the poor tissue penetration of external light sources. This study focuses on the synthesis, characterization, and evaluation of the effect of temozolomide co-encapsulated radio-PDT nanoparticles for the treatment of glioblastoma.
Material and Methods: An inorganic nanoscintillator was synthesized, and its comprehensive physicochemical characterization was assessed using electron dispersive x-ray spectroscopy (EDS), Transmission Electron microscopy (TEM), and X-ray diffraction (XRD) to evaluate the evolution of composition, size, and structure. The nanoscintillator was encapsulated with the photosensitizer protoporphyrin IX (PPIX), in combination with Temozolomide (TMZ), in a nanocarrier of PEG-PLGA. The characteristics of nanoparticles was assessed using TEM, Dynamic light scattering (DLS), and zeta potential was recorded. The tumor cytotoxicity of these nanoparticles was evaluated in vitro by using the U251 cell line. Furthermore, the molecular mechanism was elucidated using western blot.
Results:Our results showed the size of 15±5 for nanoscentilator, which was encapsulated with PPIX and temozolomide in the nanocarrier PEG-PLGA. The final nanocomposite was 100±10 with a Zeta potential (ZP) of -21.5. These nanoparticles demonstrated significant cytotoxicity against tumor cells compared to the control condition. Western blot analysis showed, decrease in the expression of AKT, PERK, and BCL2, while an increased expression of cleaved caspase 3 in radioPDT and TMZ Co-encapsulated radioPDT with a low dosage of irradiation.
Conclusion: Our results support the use of TMZ Co-encapsulated radioPDT and radioPDT with radiation can be used as an efficient approach for deep-seated tumors in particularly radio-resistant glioblastoma. These nanoparticles exhibited excellent biocompatibility, effective cytotoxicity towards tumor cells, and potential for translation into an in vivo tumor study.
利益披露 Disclosure
M. Rafiq, None..
D. Dinakaran, None.