A biophysical study on the mechanism of interactions of DOX or PTX with α-lactalbumin as a delivery carrier.
A biophysical study on the mechanism of interactions of DOX or PTX with α-lactalbumin as a delivery carrier.
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DOI：
10.1038/s41598-018-35559-1
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发表时间：
2018-11-26
影响因子：
4.6
通讯作者：
Saboury AA
中科院分区：
文献类型：
--
作者：
Delavari B;Mamashli F;Bigdeli B;Poursoleiman A;Karami L;Zolmajd-Haghighi Z;Ghasemi A;Samaei-Daryan S;Hosseini M;Haertlé T;Muronetz VI;Halskau Ø;Moosavi-Movahedi AA;Goliaei B;Rezayan AH;Saboury AA
多柔比星和紫杉醇是两种疏水性化疗剂，用于癌症治疗。α-乳清蛋白的疏水斑块和柔性折叠的存在可能使其成为疏水药物的合适载体。在本研究中，应用各种热力学、光谱、计算和细胞技术来评估α-乳白蛋白作为阿霉素和紫杉醇载体的潜力。根据等温滴定量热法数据，α-乳白蛋白与多柔比星或紫杉醇之间的相互作用是自发的，α-乳白蛋白与紫杉醇相互作用的K（M−1）值高于多柔比星。差示扫描量热法和各向异性结果表明α-乳白蛋白与阿霉素或紫杉醇形成复合物。分子对接和动力学研究表明TRP不参与α-Lac与阿霉素的相互作用，而TRP 60与紫杉醇的相互作用。基于测定蛋白质热稳定性的Pace分析，多柔比星和紫杉醇分别诱导α-乳白蛋白的较高和较低的热稳定性。荧光寿命测定结果表明，α-乳白蛋白与阿霉素和紫杉醇的相互作用是静态的。因此，作者假设α-乳白蛋白可作为多柔比星和紫杉醇的载体，通过降低细胞毒性和细胞凋亡，这在我们的体外细胞研究中得到证实。
Doxorubicin and paclitaxel, two hydrophobic chemotherapeutic agents, are used in cancer therapies. Presence of hydrophobic patches and a flexible fold could probably make α-Lactalbumin a suitable carrier for hydrophobic drugs. In the present study, a variety of thermodynamic, spectroscopic, computational, and cellular techniques were applied to assess α-lactalbumin potential as a carrier for doxorubicin and paclitaxel. According to isothermal titration calorimetry data, the interaction between α-lactalbumin and doxorubicin or paclitaxel is spontaneous and the K (M−1) value for the interaction of α-lactalbumin and paclitaxel is higher than that for doxorubicin. Differential scanning calorimetry and anisotropy results indicated formation of α-lactalbumin complexes with doxorubicin or paclitaxel. Furthermore, molecular docking and dynamic studies revealed that TRPs are not involved in α-Lac’s interaction with Doxorubicin while TRP 60 interacts with paclitaxel. Based on Pace analysis to determine protein thermal stability, doxorubicin and paclitaxel induced higher and lower thermal stability in α-lactalbumin, respectively. Besides, fluorescence lifetime measurements reflected that the interaction between α-lactalbumin with doxorubicin or paclitaxel was of static nature. Therefore, the authors hypothesized that α-lactalbumin could serve as a carrier for doxorubicin and paclitaxel by reducing cytotoxicity and apoptosis which was demonstrated during our in vitro cell studies.
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影响因子：
3.3
作者：
Chakraborti, Soumyananda;Sarwar, Shamila;Chakrabarti, Pinak
通讯作者：
Chakrabarti, Pinak
DOI：
10.1002/prot.340220410
发表时间：
1995-08-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
GOMEZ, J;HILSER, VJ;FREIRE, E
通讯作者：
FREIRE, E
影响因子：
3.4
作者：
Chattopadhyay, A
通讯作者：
Chattopadhyay, A
影响因子：
3
作者：
Duan, Y;Wu, C;Kollman, P
通讯作者：
Kollman, P
影响因子：
4.4
作者：
ESSMANN, U;PERERA, L;PEDERSEN, LG
通讯作者：
PEDERSEN, LG