A functional nanocarrier that copenetrates extracellular matrix and multiple layers of tumor cells for sequential and deep tumor autophagy inhibitor and chemotherapeutic delivery
A functional nanocarrier that copenetrates extracellular matrix and multiple layers of tumor cells for sequential and deep tumor autophagy inhibitor and chemotherapeutic delivery
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一种功能性纳米载体，可共渗透细胞外基质和多层肿瘤细胞，用于顺序和深层肿瘤自噬抑制剂和化疗药物递送
DOI：
10.1080/15548627.2016.1256523
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发表时间：
2017-02
期刊：
影响因子：
13.3
通讯作者：
He Qin
中科院分区：
文献类型：
--
作者：
Wang Yang;Qiu Yue;Yin Sheng;Zhang Li;Shi Kairong;Gao Huile;Zhang Zhirong;He Qin
摘要为了进一步增强肿瘤深部给药的强度并整合联合治疗，我们在此报道了一种核-壳纳米载体，其可以同时克服细胞外基质（ECM）和多层肿瘤细胞（MLTC）的双重屏障。开发了pH触发的可逆溶胀-收缩核和MMP 2（基质金属肽酶2）可降解壳，以分别包封化疗药物和大自噬/自噬抑制剂。MMP 2降解壳，随后是自噬抑制剂的释放。暴露的核心可以沿着ECM内的孔扩散以将化疗剂递送到深部肿瘤中，并且它能够在溶酶体中膨胀并在细胞质或ECM中收缩。核心的肿胀导致化疗药物的快速释放，以杀死自噬抑制细胞。在离开死细胞后，收缩的核心可以作用于更靠近肿瘤中心的相邻细胞。因此，核心也可以一层一层地穿过MLTC，将化疗药物递送到深部肿瘤中。
ABSTRACT To further enhance the intensity of deep tumor drug delivery and integrate a combined therapy, we herein report on a core-shell nanocarrier that could simultaneously overcome the double barriers of the extracellular matrix (ECM) and multiple layers of tumor cells (MLTC). A pH-triggered reversible swelling-shrinking core and an MMP2 (matrix metallopeptidase 2) degradable shell were developed to encapsulate chemotherapeutics and macroautophagy/autophagy inhibitors, respectively. MMP2 degraded the shell, which was followed by the autophagy inhibitors' release. The exposed core could diffuse along the pore within the ECM to deliver chemotherapeutics into deep tumors, and it was able to swell in lysosomes and shrink back in the cytoplasm or ECM. The swelling of the core resulted in the rapid release of chemotherapeutics to kill autophagy-inhibited cells. After leaving the dead cells, the shrinking core could act on neighboring cells that were closer to the center of the tumor. The core thus could also cross MLTC layer by layer to deliver chemotherapeutics into the deep tumor.
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影响因子：
2.5
作者：
Dean, Michael
通讯作者：
Dean, Michael
影响因子：
16.1
作者：
Li, Yinghuan;Wang, Jie;Wientjes, M. Guillaume;Au, Jessie L. -S.
通讯作者：
Au, Jessie L. -S.
负载多西他赛的树枝状共聚物纳米粒子与自噬抑制剂联合治疗增强乳腺癌的治疗效果
影响因子：
12.4
作者：
Zhang X;Yang Y;Liang X;Zeng X;Liu Z;Tao W;Xiao X;Chen H;Huang L;Mei L
通讯作者：
Mei L
影响因子：
3
作者：
Serda, Rita E.;Godin, Biana;Blanco, Elvin;Chiappini, Ciro;Ferrari, Mauro
通讯作者：
Ferrari, Mauro
影响因子：
17.1
作者：
Huang K;Ma H;Liu J;Huo S;Kumar A;Wei T;Zhang X;Jin S;Gan Y;Wang PC;He S;Zhang X;Liang XJ
通讯作者：
Liang XJ