Ultrasound-visualized nanocarriers with siRNA for targeted inhibition of M2-like TAM polarization to enhance photothermal therapy in NSCLC

Ultrasound-visualized nanocarriers with siRNA for targeted inhibition of M2-like TAM polarization to enhance photothermal therapy in NSCLC
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带有 siRNA 的超声可视化纳米载体可靶向抑制 M2 样 TAM 极化,从而增强 NSCLC 的光热治疗

DOI:
10.1007/s12274-022-4767-7
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发表时间:
2022-08
期刊:
Springer Nature
影响因子:
--
通讯作者:
Juan Li
Juan Li
中科院分区:
其他
文献类型:
--
作者:
Wenhao Lv;Chen Xu;Hao Wu;Yangyang Zhu;Ozioma Udochukwu Akakuru;Hui Du;Fang Nie;Aiguo Wu;Juan Li

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光热疗法(PTT)作为一种有前途的快速消除肿瘤的策略受到了广泛关注。然而,在治疗过程中不可避免的炎症反应可能导致高浓度的M2样肿瘤相关巨噬细胞(TAM),增加肿瘤复发和转移的风险。为了解决这个问题,金基纳米载体(PGMP-small interfering RNA(siRNA)nanoparticles(NPs))含有STAT 6 siRNA,抑制M2-like TAM极化,设计和研究用于PTT和非小细胞肺癌(NSCLC)的基因治疗。在NSCLC模型中,纳米载体表现出优异的siRNA递送能力和在巨噬细胞中高达90%的高基因转染率,从而抑制约87%的M2样TAM的极化,并有效抑制NSCLC的侵袭和转移。同时,独特的金纳米球结构提供了改进的PTT和对比增强的超声成像,从而有助于有效消除和实时监测肿瘤组织。这些具有基因和光热联合治疗能力的纳米载体提高了单一模式治疗的疗效,并显示出抑制癌细胞复发和转移以最终治愈NSCLC的潜力。
Photothermal therapy (PTT) has received a lot of attention as a promising strategy for eliminating tumors quickly. However, the unavoidable inflammatory response during the treatment might result in a high concentration of M2-like tumor-associated macrophages (TAMs), increasing the risk of tumor recurrence and metastasis. To address this problem, gold-based nanocarriers (PGMP-small interfering RNA (siRNA) nanoparticles (NPs)) containing STAT6siRNA, that inhibited M2-like TAM polarization, were designed and investigated for PTT and gene therapy of non-small cell lung cancer (NSCLC). In an NSCLC model, the nanocarriers demonstrated excellent siRNA delivery ability and a high gene transfection rate of up to 90% in macrophages, thus inhibiting the polarization of about 87% of M2-like TAMs and effectively suppressing the invasion and metastasis of NSCLC. Meanwhile, the unique gold nanosphere structure offered improved PTT and contrast-enhanced ultrasound imaging, thus contributing to the efficient elimination and real-time monitoring of the tumor tissues. These nanocarriers with combined gene and photothermal therapeutic capabilities improved the efficacy of single-modality treatment, and showed the potential to inhibit cancer cell recurrence and metastasis to ultimately cure NSCLC.
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