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Charge Reversion Simultaneously Enhances Tumor Accumulation and Cell Uptake of Layered Double Hydroxide Nanohybrids for Effective Imaging and Therapy.
Small ( IF 13.0 ) Pub Date : 2020-06-30 , DOI: 10.1002/smll.202002115
Jianping Liu 1 , Yilun Wu 1 , Changkui Fu 1 , Bei Li 1 , Li Li 1 , Run Zhang 1 , Tiefeng Xu 2 , Zhi Ping Xu 1
Affiliation  

Nanotheranostics have been actively sought in precision nanomedicine in recent years. However, insufficient tumor accumulation and limited cell uptake often impede the nanotheranostic efficacy. Herein, pH‐sensitive charge‐reversible polymer‐coated layered double hydroxide (LDH) nanohybrids are devised to possess long circulation in blood but reserve surface charges in the weakly acidic tumor tissue to re‐expose therapeutic LDH nanoparticles for enhanced tumor accumulation and cell uptake. In vitro experimental data demonstrate that charge‐reversible nanohybrids mitigate the cell uptake in physiological conditions (pH 7.4), but remarkably facilitate internalization by tumor cells after charge reversion in the weakly acidic environment (pH 6.8). More significantly, about 6.0% of injected charge‐reversible nanohybrids accumulate in the tumor tissue at 24 h post injection, far higher than the average accumulation (0.7%) reported elsewhere for nanoparticles. This high tumor accumulation clearly shows the tumor tissues in T1‐weighted magnetic resonance imaging. As a consequence, >95% inhibition of tumor growth in the B16F0‐bearing mouse model is achieved via only one treatment combining RNAi and photothermal therapy under very mild irradiation (808 nm laser, 0.3 W cm−2 for 180 s). The current research thus demonstrates a new strategy to functionalize nanoparticles and simultaneously enhance their tumor accumulation and cell internalization for effective cancer theranostics.

中文翻译:

电荷逆转同时增强了肿瘤的积累和层状双氢氧化物纳米杂化物的细胞摄取,从而有效地进行了成像和治疗。

近年来,精密纳米医学一直在积极寻求纳米治疗。然而,不足的肿瘤积累和有限的细胞摄取常常阻碍纳米热疗功效。本文设计了对pH敏感的电荷可逆聚合物涂层双氢氧化物(LDH)纳米杂合物,使其在血液中具有较长的循环时间,但在弱酸性肿瘤组织中保留了表面电荷,以重新暴露治疗性LDH纳米颗粒,从而增强了肿瘤的积累和细胞摄取。 。体外实验数据表明,可逆电荷的杂合体可在生理条件下(pH 7.4)减轻细胞摄取,但在弱酸性环境(pH 6.8)下电荷逆转后可显着促进肿瘤细胞的内在化。更重要的是,大约为6。注射后24小时,注射的电荷可逆纳米杂化物中有0%积聚在肿瘤组织中,远高于其他地方报道的纳米粒子的平均积聚(0.7%)。如此高的肿瘤积聚清楚地显示了T中的肿瘤组织1加权磁共振成像。结果,在非常轻度的照射下(808 nm激光,0.3 W cm -2持续180 s),仅通过一种结合RNAi和光热疗法的治疗,就可以在B16F0荷瘤小鼠模型中实现> 95%的肿瘤生长抑制。因此,当前的研究表明了一种新的策略,可以对纳米粒子进行功能化,并同时增强其肿瘤积累和细胞内在化,从而有效地治疗癌症。
更新日期:2020-08-06
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