Biodegradable polymeric nanoparticles show high efficacy and specificity at DNA delivery to human glioblastoma in vitro and in vivo.
Biodegradable polymeric nanoparticles show high efficacy and specificity at DNA delivery to human glioblastoma in vitro and in vivo.
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DOI：
10.1021/nn501197v
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发表时间：
2014-05-27
期刊：
影响因子：
17.1
通讯作者：
Green, Jordan J.
中科院分区：
文献类型：
--
作者：
Guerrero-Cazares, Hugo;Tzeng, Stephany Y.;Young, Noah P.;Abutaleb, Ameer O.;Quinones-Hinojosa, Alfredo;Green, Jordan J.
目前的胶质母细胞瘤疗法不足以预防肿瘤复发和最终死亡。在这里，我们描述了一种使用可生物降解的聚（β-氨基酯）（PBAE）通过非病毒DNA递送治疗恶性胶质瘤的方法，重点关注脑肿瘤起始细胞（BTIC），这种肿瘤细胞群被认为是导致新肿瘤形成和对许多传统疗法产生耐药性的原因。我们在体外原代人 BTIC 中显示出 >60% 的转染效率和较低的生物材料介导的细胞毒性，即使 BTIC 生长为 3-D 甲球体也是如此。有趣的是，我们发现这些聚合物纳米颗粒对原代人类 BTIC 的非病毒转染相对于原代健康人类神经祖细胞表现出内在特异性，并且这种特异性并不是由于纳米颗粒的细胞生长速率或总细胞摄取的差异所致。此外，我们证明可生物降解的 PBAE/DNA 纳米粒子可以被制造、冻干，然后储存至少 2 年而不会失去功效，从而增加了该技术的转化相关性。使用冻干纳米粒子，我们显示肿瘤细胞在瘤内注射到人胶质母细胞瘤原位小鼠模型中后的转基因表达。 PBAE/DNA纳米粒子在体内外源基因表达方面比裸露DNA更有效，并且体内肿瘤细胞比未侵袭的脑实质更有效地转染。这项工作展示了非病毒基因传递工具针对人类脑肿瘤的潜力。
Current glioblastoma therapies are insufficient to prevent tumor recurrence and eventual death. Here, we describe a method to treat malignant glioma by nonviral DNA delivery using biodegradable poly(β-amino ester)s (PBAEs), with a focus on the brain tumor initiating cells (BTICs), the tumor cell population believed to be responsible for the formation of new tumors and resistance to many conventional therapies. We show transfection efficacy of >60% and low biomaterial-mediated cytotoxicity in primary human BTICs in vitro even when the BTICs are grown as 3-D oncospheres. Intriguingly, we find that these polymeric nanoparticles show intrinsic specificity for nonviral transfection of primary human BTICs over primary healthy human neural progenitor cells and that this specificity is not due to differences in cellular growth rate or total cellular uptake of nanoparticles. Moreover, we demonstrate that biodegradable PBAE/DNA nanoparticles can be fabricated, lyophilized, and then stored for at least 2 years without losing efficacy, increasing the translational relevance of this technology. Using lyophilized nanoparticles, we show transgene expression by tumor cells after intratumoral injection into an orthotopic murine model of human glioblastoma. PBAE/DNA nanoparticles were more effective than naked DNA at exogenous gene expression in vivo, and tumor cells were transfected more effectively than noninvaded brain parenchyma in vivo. This work shows the potential of nonviral gene delivery tools to target human brain tumors.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
15
作者：
Bishop, Corey J.;Ketola, Tiia-Maaria;Tzeng, Stephany Y.;Sunshine, Joel C.;Urtti, Arto;Lemmetyinen, Helge;Vuorimaa-Laukkanen, Elina;Yliperttula, Marjo;Green, Jordan J.
通讯作者：
Green, Jordan J.
影响因子：
4.1
作者：
McGirt MJ;Than KD;Weingart JD;Chaichana KL;Attenello FJ;Olivi A;Laterra J;Kleinberg LR;Grossman SA;Brem H;Quiñones-Hinojosa A
通讯作者：
Quiñones-Hinojosa A
影响因子：
4.1
作者：
Chaichana KL;Zadnik P;Weingart JD;Olivi A;Gallia GL;Blakeley J;Lim M;Brem H;Quiñones-Hinojosa A
通讯作者：
Quiñones-Hinojosa A
通过与叶酸和细胞穿透肽八精氨酸偶联的阳离子聚合物纳米载体将基因递送至肿瘤细胞
影响因子：
14
作者：
Jiang, Qi-Ying;Lai, Li-Hua;Tang, Gu-Ping
通讯作者：
Tang, Gu-Ping