Smart Nanotransformers with Unique Enzyme-Inducible Structural Changes and Drug Release Properties.
Smart Nanotransformers with Unique Enzyme-Inducible Structural Changes and Drug Release Properties.
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DOI：
10.1021/acs.biomac.6b00227
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发表时间：
2016-06-13
影响因子：
6.2
通讯作者：
Law B
中科院分区：
文献类型：
--
作者：
Bellat V;Lee HH;Vahdat L;Law B
我们之前报道了一种高长径比的肽纳米纤维，它可以有效地递送到肿瘤中，而其他器官的非特异性摄取极小。多肽的性质提供了独特的响应智能配方的设计灵活性。本文报道了两种性能与纳米变压器（NTFs）一致的新配方。NTF1和NTF2可以在酶激活后进行生物力学重塑，分别在溶酶体腔室内产生可降解和可聚集的作用。这些NTFs被进一步评估为微管抑制剂mertansine （DM1）的载体。负载dm1的NTF1可以被组织蛋白酶B （CathB）降解，释放出相同的活性代谢物，如先前在抗体dm1偶联物的溶酶体降解中所述。相比之下，CathB只能部分消化dm1负载的NTF2，并诱导形成聚集体，成为具有缓慢载荷释放特性的储层。负载dm1的NTF1显示出与游离药物相当的细胞毒性，并且在根除三阴性乳腺癌方面比NTF2配方更有效。我们的数据表明，具有不同酶诱导结构变化和有效载荷释放谱的生物转换器可以设计用于细胞毒性和显像剂的细胞内递送。
We previously reported a high aspect ratio peptide nanofiber that could be effectively delivered to tumors with minimal nonspecific uptake by other organs. The peptidic nature offers the design flexibility of smart formulation with unique responsiveness. Two new formulations that behave congruously as nanotransformers (NTFs) are reported herein. NTF1 and NTF2 could biomechanically remodel upon enzyme activation to generate a degradable and an aggregable effect, respectively, within the lysosomal compartment. These NTFs were further evaluated as carriers of mertansine (DM1), a microtubule inhibitor. DM1-loaded NTF1 could be degraded by cathepsin B (CathB) to release the same active metabolite, as previously described in the lysosomal degradation of antibody-DM1 conjugate. In contrast, CathB only partially digested DM1-loaded NTF2 and induced aggregate formation to become a storage reservoir with slow payload release property. The DM1-loaded NTF1 exhibited a comparable cytotoxicity to the free drug and was more effective than the NTF2 formulation in eradicating triple negative breast cancer. Our data suggested that biological transformers with distinct enzyme-induced structural changes and payload release profiles could be designed for the intracellular delivery of cytotoxic and imaging agents.
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影响因子：
16.6
作者：
通讯作者：
--
DOI：
10.1016/j.jconrel.2011.10.016
发表时间：
2012-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Chu DS;Johnson RN;Pun SH
通讯作者：
Pun SH
组织蛋白酶B促进结直肠肿瘤发生，细胞侵袭和转移。
影响因子：
4.6
作者：
Bian B;Mongrain S;Cagnol S;Langlois MJ;Boulanger J;Bernatchez G;Carrier JC;Boudreau F;Rivard N
通讯作者：
Rivard N
影响因子：
11.2
作者：
Erickson, HK;Park, PU;Blättler, WA
通讯作者：
Blättler, WA
DOI：
10.1016/j.ejogrb.2014.12.020
发表时间：
2015-02-01
影响因子：
2.6
作者：
Gogiel, Tomasz;Wolanska, Malgorzata;Romanowicz, Lech
通讯作者：
Romanowicz, Lech