Switching of Self-Assembly in a Peptide Nanostructure with a Specific Enzyme.
Switching of Self-Assembly in a Peptide Nanostructure with a Specific Enzyme.
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DOI：
10.1039/c1sm05610g
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发表时间：
2011-10-21
期刊：
影响因子：
3.4
通讯作者：
Stupp SI
中科院分区：
文献类型：
--
作者：
Webber MJ;Newcomb CJ;Bitton R;Stupp SI
多肽自组装已被证明是制备生物活性纳米结构的有用工具，最近的研究也证明了它们在再生医学治疗方面的潜力。原则上，使这些纳米结构更具仿生学性的一个途径是在其分子设计中加入生物传感能力。我们在这里报告了使用可逆的酶触发器来控制肽两亲体（PA）纳米结构的组装和拆卸。这些研究中使用的PA含有一个一致的蛋白激酶a （PKA）特异性底物序列，PKA是一种对细胞内信号传导很重要的生物酶，也被证明是细胞外癌症生物标志物。经PKA处理后，这种PA分子被磷酸化，导致高纵横比丝状PA纳米结构解体。用酶裂解磷酸基导致丝状纳米结构的重组。我们还表明，在PKA存在下的分解允许酶触发的封装癌症药物的释放。此外，这些载药纳米结构被发现在已知分泌高水平PKA的癌细胞系中诱导优先细胞毒性。这种通过酶开关控制纳米结构的能力可以制备高度复杂的仿生材料，这些材料具有生物传感能力，可以实现治疗特异性。
Peptide self-assembly has been shown to be a useful tool for the preparation of bioactive nanostructures, and recent work has demonstrated their potential as therapies for regenerative medicine. In principle, one route to make these nanostructures more biomimetic would be to incorporate in their molecular design the capacity for biological sensing. We report here on the use of a reversible enzymatic trigger to control the assembly and disassembly of peptide amphiphile (PA) nanostructures. The PA used in these studies contained a consensus substrate sequence specific to protein kinase A (PKA), a biological enzyme important for intracellular signaling that has also been shown to be an extracellular cancer biomarker. Upon treatment with PKA, this PA molecule becomes phosphorylated causing the high aspect-ratio filamentous PA nanostructures to disassemble. Treatment with an enzyme to cleave the phosphate group results in reformation of the filamentous nanostructures. We also show that disassembly in the presence of PKA allows the enzyme-triggered release of an encapsulated cancer drug. In addition, these drug-loaded nanostructures were found to induce preferential cytotoxicity in a cancer cell line that is known to secrete high levels of PKA. This ability to control nanostructure through an enzymatic switch could allow for the preparation of highly sophisticated and biomimetic materials that incorporate a biological sensing capability to enable therapeutic specificity.
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影响因子：
4.9
作者：
Koga, Tomoyuki;Kitamura, Ken-ichi;Higashi, Nobuyuki
通讯作者：
Higashi, Nobuyuki
影响因子：
14
作者：
Ghanaati, Shahram;Webber, Matthew J.;Unger, Ronald E.;Orth, Carina;Hulvat, James F.;Kiehna, Sarah E.;Barbeck, Mike;Rasic, Angela;Stupp, Samuel I.;Kirkpatrick, C. James
通讯作者：
Kirkpatrick, C. James
影响因子：
15
作者：
Muraoka, Takahiro;Cui, Honggang;Stupp, Samuel I.
通讯作者：
Stupp, Samuel I.
DOI：
10.1016/j.bbadis.2005.12.010
发表时间：
2006-04-01
影响因子：
6.2
作者：
Nesterova, M;Johnson, N;Cho-Chung, YS
通讯作者：
Cho-Chung, YS
影响因子：
6.2
作者：
Guler, Mustafa O.;Hsu, Lorraine;Stupp, Samuel I.
通讯作者：
Stupp, Samuel I.