Cell penetrating peptide conjugated bioreducible polymer for siRNA delivery.
Cell penetrating peptide conjugated bioreducible polymer for siRNA delivery.
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DOI：
10.1016/j.biomaterials.2011.03.058
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发表时间：
2011-08
期刊：
影响因子：
14
通讯作者：
Bull, David A.
中科院分区：
文献类型：
--
作者：
Nam, Hye Yeong;Kim, Jaesung;Kim, Soojin;Yockman, James W.;Kim, Sung Wan;Bull, David A.
将主要的心肌细胞特异性多肽(PCM)和细胞穿透性多肽(CPP)HIV-TAT(49-57)掺入到半胺双丙烯酰胺-二氨基己烷(CBA-DAH)聚合物中，以增加RNAi向靶细胞，特别是心肌细胞的递送。有趣的是，PCM和TAT结合对H9C2大鼠心肌细胞摄取和转染率的影响大于NIH3T3细胞。我们用PCM和TAT修饰的聚(CBA-DAH)(PCM-CD-TAT)研究了针对SHP-1或Fas的siRNA在低氧条件下抑制心肌细胞凋亡的可能性。为评价Fas siRNA/聚合物或SHP-1 siRNA/聚合物对心肌细胞凋亡的抑制作用，将Fas siRNA/聚合物或SHP-1 siRNA/聚合物分别导入低氧和无血清处理的心肌细胞。在低氧条件下孵育后，用SHP-1siRNA复合体或Fas siRNA复合体处理后，细胞存活率增加，LDH细胞毒性降低。Annexin V-FITC/PI染色显示，任何一种siRNA多聚体的细胞凋亡率都较低。SHP-1 siRNA/PCM-CD-TAT复合体和Fas siRNA/PCM-CD-TAT复合体作为抑制心肌细胞凋亡的治疗剂值得进一步研究。
The primary cardiomyocyte–specific peptide (PCM) and the cell–penetrating peptide (CPP), HIV-Tat (49-57), were incorporated into the polymer, cystamine bisacrylamide-diaminohexane (CBA-DAH), to increase the delivery of RNAi to target cells, specifically cardiomyocytes. Interestingly, the impact of PCM and Tat conjugation on cellular uptake and transfection efficiency was greater in H9C2 rat cardiomyocytes than in NIH 3T3 cells. We examined the potential for siRNA targeting SHP-1 or Fas to inhibit the apoptosis of cardiomyocytes under hypoxic conditions using PCM and Tat-modified poly(CBA-DAH), (PCM-CD-Tat). To evaluate for efficacy in inhibiting apoptosis, either Fas siRNA/polymer or SHP-1 siRNA/polymer were transfected into cardiomyocytes treated under hypoxic and serum-deprived conditions. After incubation under hypoxic conditions, treatment with either the SHP-1siRNA complex or the Fas siRNA complex resulted in an increase in cell viability and a reduction in LDH cytotoxicity. The cells transfected with either of the siRNA polyplexes had a lower incidence of apoptosis as demonstrated by Annexin V–FITC/PI staining. Both the SHP-1 siRNA/PCM-CD-Tat complex and the Fas siRNA/PCM-CD-Tat complex warrant further investigation as therapeutic agents to inhibit the apoptosis of cardiomyocytes.
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影响因子：
10.8
作者：
Granata, Riccarda;Trovato, Letizia;Ghigo, Ezio
通讯作者：
Ghigo, Ezio
影响因子：
4.1
作者：
Aigner, A
通讯作者：
Aigner, A
DOI：
10.1152/ajpheart.00777.2002
发表时间：
2003-02-01
影响因子：
4.8
作者：
Lee, P;Sata, M;Kitsis, RN
通讯作者：
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影响因子：
4.8
作者：
Sugano, M;Tsuchida, K;Makino, N
通讯作者：
Makino, N
DOI：
10.1073/pnas.0435906100
发表时间：
2003-02-18
影响因子：
11.1
作者：
Torchilin, VP;Levchenko, TS;D'Souza, GGM
通讯作者：
D'Souza, GGM