Density functional theory-guided drug loading strategy for sensitized tumor-homing thermotherapy
Density functional theory-guided drug loading strategy for sensitized tumor-homing thermotherapy
复制标题
密度泛函理论指导的致敏肿瘤归巢热疗载药策略
DOI：
10.1016/j.cej.2021.130146
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发表时间：
2021
影响因子：
15.1
通讯作者：
Xue Wei
中科院分区：
文献类型：
--
作者：
Huo Cong-Min;Chen Liheng;Wang Hai-Yang;Luo Si-Man;Wang Xiang;Shi Yun-Feng;Zhu Jing-Yi;Xue Wei
载药与纳米载体之间的强相互作用在很大程度上决定了载药量的高，但也带来了药物有效释放的问题。为了解决这一难题，我们开发了一种密度泛函数理论（DFT）引导的药物装载策略，构建了一个可降解的纳米平台，用于致敏肿瘤归巢热疗法。DFT是一种计算方法，用于筛选热休克蛋白90 （HSP90）抑制剂格尔达霉素（GDM），该抑制剂与纳米载体结构高度匹配，从而提供了很高的载药效率（~ 42%）。特别值得注意的是，由于癌细胞膜（CCM）和聚多巴胺（PDA）的等电点都在pH 4.0 ~ 5.0左右，与内切酶/溶酶体的酸性环境完全吻合，GDM能够在肿瘤细胞内有效释放。CCM包膜使PDA/GDM@CCM能够自我靶向源癌细胞和同源肿瘤，同时有效抑制巨噬细胞的识别和清除。有效的光热消融归功于GDM对肿瘤耐热性的有效抑制和肿瘤基因组图谱（TCGA）对最佳匹配肿瘤类型的精确选择。这种dft引导的载药策略为优化载药纳米载体指明了一条新的途径，最终实现了高药物利用度和优异的疗效。
Strong interactions between loading drugs and nanocarriers contribute greatly to the high loading capacity while bringing about the problems on effective drug release. To solve this dilemma, we develop a density functional theory (DFT)-guided drug loading strategy to construct a dismountable nanoplatform for sensitized tumor-homing thermotherapy. DFT, a kind of computational method, is used to screen out a heat shock protein90 (HSP90) inhibitor, geldanamycin (GDM), that highly matched the structure of nanocarriers, thus providing a high drug loading efficiency (~ 42%). Of special note, GDM could be effectively released inside tumor cells because the isoelectric points of cancer cell membrane (CCM) and polydopamine (PDA) are both around pH 4.0 ~ 5.0, which could exactly match with the acidic environment of endo/lysosome. The CCM envelope enables self-targeting of PDA/GDM@CCM to the source cancer cells and homologous tumors while effectively inhibiting recognition and clearance by macrophages. Efficient photothermal ablation is attributed to the efficient suppression of tumor heat resistance by GDM and precise selection of the best matched tumor type by using The Cancer Genome Atlas (TCGA). This DFT-guided drug loading strategy points out a new avenue for optimization of drug-loading into nanocarriers, and ultimately contributes to the high drug availability and excellent curative effect.
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影响因子：
16.6
作者：
Bogojeski M;Vogt-Maranto L;Tuckerman ME;Müller KR;Burke K
通讯作者：
Burke K
影响因子：
26.6
作者：
Adekoya D;Qian S;Gu X;Wen W;Li D;Ma J;Zhang S
通讯作者：
Zhang S
影响因子：
5.2
作者：
Diaz-Diaz, Andrea;Roca-Lema, Daniel;Figueroa, Angelica
通讯作者：
Figueroa, Angelica
影响因子：
21.8
作者：
Falivene, Laura;Cao, Zhen;Cavallo, Luigi
通讯作者：
Cavallo, Luigi
影响因子：
15.1
作者：
Hu, Qi;Bu, Yusi;Wang, Sicen
通讯作者：
Wang, Sicen