Cathepsin-B Induced Controlled Release from Peptide-Capped Mesoporous Silica Nanoparticles

Cathepsin-B Induced Controlled Release from Peptide-Capped Mesoporous Silica Nanoparticles
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DOI:
10.1002/chem.201404382
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发表时间:
2014-11-17
影响因子:
4.3
通讯作者:
Orzaez, Mar
Orzaez, Mar
中科院分区:
化学2区
文献类型:
--
作者:
de la Torre, Cristina;Mondragon, Laura;Orzaez, Mar

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新的盖帽二氧化硅介孔纳米颗粒细胞内控制货物释放在组织蛋白酶B表达细胞被描述。合成了纳米介孔MCM-41载体,负载含有组织蛋白酶B靶肽序列的分子门的红花素O (S1-P)或阿霉素(S2-P)。固体被设计成显示“零递送”,并在组织蛋白酶B酶存在下显示货物释放,该酶在体外选择性地水解盖层肽序列。在HeLa、mef WT和mef缺乏组织蛋白酶B细胞系中也进行了控制递送的测试。当组织蛋白酶B活跃或存在时,这些细胞会释放红素O和阿霉素。用S2-P处理的细胞显示,由于纳米颗粒内化、组织蛋白酶B对封盖肽的水解和细胞毒性药物的递送,细胞活力下降,证明了这些纳米装置作为癌症治疗的新治疗工具的可能性。
New capped silica mesoporous nanoparticles for intracellular controlled cargo release within cathepsin B expressing cells are described. Nanometric mesoporous MCM-41 supports loaded with safranin O (S1-P) or doxorubicin (S2-P) containing a molecular gate based on a cathepsin B target peptidic sequence were synthesized. Solids were designed to show "zero delivery" and to display cargo release in the presence of cathepsin B enzyme, which selectively hydrolyzed in vitro the capping peptide sequence. Controlled delivery in HeLa, MEFs WT, and MEFs lacking cathepsin B cell lines were also tested. Release of safranin O and doxorubicin in these cells took place when cathepsin B was active or present. Cells treated with S2-P showed a fall in cell viability due to nanoparticles internalization, cathepsin B hydrolysis of the capping peptide, and cytotoxic agent delivery, proving the possible use of these nanodevices as new therapeutic tools for cancer treatment.