研究动态
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基于自噬抑制和光动力疗法联合化疗的多功能上转换纳米平台的构建用于抗肿瘤治疗。

Construction of a Multifunctional Upconversion Nanoplatform Based on Autophagy Inhibition and Photodynamic Therapy Combined with Chemotherapy for Antitumor Therapy.

发表日期:2024 Aug 06
作者: Fang Ning, Dengshuai Wei, Hongli Yu, Tingting Song, Zhipeng Li, Hongmei Ma, Yong Sun
来源: MOLECULAR PHARMACEUTICS

摘要:

抑制自噬可增加肿瘤细胞对放疗和化疗的敏感性,提高肿瘤的治疗效果。最近,光动力疗法(PDT)联合化疗已被证明可以进一步提高癌症治疗的效率。因此,将自噬抑制与 PDT 和化疗相结合可能代表一种潜在有效的癌症治疗新策略。然而,目前广泛研究的自噬抑制剂由于其固有的药理活性,不可避免地会产生各种毒副作用。为了克服这一限制,在本研究中,我们设计了一种理想的多功能上转换纳米平台,UCNP-Ce6-EPI@mPPA NIR (MUCEN)。对照、UCNP-EPI@mPPA (MUE)、UCNP-EPI@mPPA NIR (MUEN)、Ce6-EPI@mPPA (MCE)、Ce6-EPI@mPPA NIR (MCEN) 和 UCNP-Ce6-EPI@mPPA (MUCE) ) 组分别设置为对照组。基于自噬抑制和PDT相结合,MUCEN的平均粒径为197 nm,可以同时实现氯e6(Ce6)和表阿霉素(EPI)的双重封装。体外测试表明,在近红外光照射下,4T1细胞可以有效地内吞MUCE。此外,体内测试表明 MUCE 显着抑制肿瘤生长。免疫组织化学结果表明,MUCE有效增加肿瘤组织中自噬抑制剂p62和LC3的表达。自噬抑制和 PDT 与 MUCE 的协同作用表现出优异的肿瘤抑制作用,为癌症治疗提供了一种创新方法。
Inhibition of autophagy increases the sensitivity of tumor cells to radiotherapy and chemotherapy and improves the therapeutic effect on tumors. Recently, photodynamic therapy (PDT) combined with chemotherapy has been proven to further improve the efficiency of cancer treatment. As such, combining autophagy inhibition with PDT and chemotherapy may represent a potentially effective new strategy for cancer treatment. However, currently widely studied autophagy inhibitors inevitably produce various toxic side effects due to their inherent pharmacological activity. To overcome this constraint, in this study, we designed an ideal multifunctional upconversion nanoplatform, UCNP-Ce6-EPI@mPPA + NIR (MUCEN). Control, UCNP-EPI@mPPA (MUE), UCNP-EPI@mPPA + NIR (MUEN), Ce6-EPI@mPPA (MCE), Ce6-EPI@mPPA + NIR (MCEN), and UCNP-Ce6-EPI@mPPA (MUCE) groups were set up separately as controls. Based on a combination of autophagy inhibition and PDT, the average particle size of MUCEN was 197 nm, which can simultaneously achieve the double encapsulation of chlorine e6 (Ce6) and epirubicin (EPI). In vitro tests revealed that MUCE was efficiently endocytosed by 4T1 cells under near-infrared light irradiation. Further, in vivo tests revealed that MUCE dramatically inhibited tumor growth. Immunohistochemistry results indicated that MUCE efficiently increased the expression of autophagy inhibitors p62 and LC3 in tumor tissues. The synergistic effect of autophagy inhibition and PDT with MUCE exhibited superior tumor suppression, providing an innovative approach to cancer treatment.