Cell penetrating peptides fused to a thermally targeted biopolymer drug carrier improve the delivery and antitumor efficacy of an acid-sensitive doxorubicin derivative.
Cell penetrating peptides fused to a thermally targeted biopolymer drug carrier improve the delivery and antitumor efficacy of an acid-sensitive doxorubicin derivative.
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DOI：
10.1016/j.ijpharm.2012.07.043
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发表时间：
2012-10-15
影响因子：
5.8
通讯作者：
Raucher D
中科院分区：
文献类型：
--
作者：
Walker L;Perkins E;Kratz F;Raucher D
弹性蛋白样多肽(ELP)是一种具有热响应性的大分子载体，可在实体肿瘤中被动积聚，在高温下可在肿瘤组织中聚集。在这项研究中，ELP与抗癌药物阿霉素(Doxo)和三种不同的细胞穿透肽(CPP)偶联，以抑制小鼠肿瘤生长，并与游离阿霉素进行比较。在MCF-7乳腺癌细胞中的荧光显微镜研究表明，三种不同的CPP-ELP-Doxo结合物将阿霉素输送到细胞核。在42℃时，所有结合物均具有细胞毒性，IC50值为12~30μM，但以SynB1为细胞穿透肽的ELP载体的固有细胞毒性最低。因此，将SynB1-ELP-Doxo与阿霉素在高温条件下的抗肿瘤效果进行了比较。C57BL/6雌性荷E0771小鼠乳腺肿瘤用游离阿霉素或SynB1-ELP-Doxo结合物联合或不联合聚焦热疗治疗。在高温条件下，SynB1-ELP-Doxo的肿瘤抑制率是同等剂量的游离阿霉素治疗下的2倍，因此是优化温度响应性药物聚合物结合物的一个有前途的候选药物。
Elastin-like polypeptide (ELP) is a macromolecular carrier with thermally responsive properties that can passively accumulate in solid tumors and additionally aggregate in tumor tissue when exposed to hyperthermia. In this study, ELP was conjugated to the anticancer drug doxorubicin (DOXO) and three different cell-penetrating peptides (CPP) in order to inhibit tumor growth in mice compared to free doxorubicin. Fluorescence microscopy studies in MCF-7 breast carcinoma cells demonstrated that the three different CPP-ELP-DOXO conjugates delivered doxorubicin to the cell nucleus. All CPP-ELP-DOXO conjugates showed cytotoxicity with IC50 values in the range of 12-30 μM at 42 °C, but the ELP carrier with SynB1 as the cell-penetrating peptide had the lowest intrinsic cytotoxicity. Therefore, the antitumor efficacy of SynB1-ELP-DOXO was compared to doxorubicin under hyperthermic conditions. C57BL/6 female mice bearing syngeneic E0771 murine breast tumors were treated with either free doxorubicin or the SynB1-ELP-DOXO conjugate with or without focused hyperthermia on the tumor. Under hyperthermic conditions, tumor inhibition with SynB1-ELP-DOXO was 2-fold higher than under therapy with free doxorubicin at the equivalent dose, and is thus a promising lead candidate for optimizing thermally responsive drug polymer conjugates.
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DOI：
10.1111/j.1432-1033.1996.0575p.x
发表时间：
1996-05-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Aumelas, A;Mangoni, M;Chavanieu, A
通讯作者：
Chavanieu, A
影响因子：
41.2
作者：
通讯作者：
--
影响因子：
5.8
作者：
Bidwell, Gene L., III;Fokt, Izabela;Raucher, Drazen
通讯作者：
Raucher, Drazen
DOI：
10.1073/pnas.93.16.8288
发表时间：
1996-08-06
影响因子：
11.1
作者：
Biersack, H;Jensen, S;Andersen, AH
通讯作者：
Andersen, AH
影响因子：
10.8
作者：
Massodi, I;Bidwell, GL;Raucher, D
通讯作者：
Raucher, D