HER2-positive breast cancer targeting and treatment by a peptide-conjugated mini nanodrug.
HER2-positive breast cancer targeting and treatment by a peptide-conjugated mini nanodrug.
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DOI：
10.1016/j.nano.2016.07.013
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Holler E
中科院分区：
文献类型：
--
作者：
Ding H;Gangalum PR;Galstyan A;Fox I;Patil R;Hubbard P;Murali R;Ljubimova JY;Holler E
HER2+ 乳腺癌是最具侵袭性的乳腺癌形式之一。合成了新的基于聚苹果酸的微型纳米药物共聚物，并专门用于抑制 HER2+ 乳腺癌的生长。这些微型纳米药物非常有效，在临床上可以替代曲妥珠单抗（已上市的治疗性抗体）和抗体靶向纳米生物复合物。新型迷你纳米药物被设计成具有细长的形状和小尺寸。 HER2+ 细胞被聚合物附着的曲妥珠单抗模拟 12 聚体肽识别。反义寡核苷酸抑制 HER2+ 细胞合成新生细胞跨膜 HER2/neu 受体，从而阻止癌细胞增殖，并且与未治疗的对照组或 PBS 治疗组相比，肿瘤大小显着减小 15 倍以上。我们强调，微型纳米药物的形状和尺寸可以增强对多个生物屏障的渗透，以促进高效的治疗。用模拟肽替代曲妥珠单抗有利于降低生产成本和技术投入，并且免疫反应可以忽略不计。通过组织和细胞生物屏障的纳米药物运输功效取决于载体的尺寸和形状。使用与微小靶向分子和药物缀合的细长聚合物，我们使用带有特定模拟肽的微型纳米药物取代了 HER2+ 抗体，从而提高了 HER2+ 乳腺癌的递送和治疗效果。
HER2+ breast cancer is one of the most aggressive forms of breast cancer. The new polymalic acid-based mini nanodrug copolymers are synthesized and specifically characterized to inhibit growth of HER2+ breast cancer. These mini nanodrugs are highly effective and in the clinic may substitute for trastuzumab (the marketed therapeutic antibody) and antibody targeted nanobiocongugates. Novel mini nanodrugs are designed to have slender shape and small size. HER2+ cells were recognized by the polymer-attached trastuzumab-mimetic 12-mer peptide. Synthesis of the nascent cell-transmembrane HER2/neu receptors by HER2+ cells was inhibited by antisense oligonucleotides that prevented cancer cell proliferation and significantly reduced tumor size by more than 15 times vs. untreated control or PBS-treated group. We emphasize that the shape and size of mini nanodrugs can enhance penetration of multiple bio-barriers to facilitate highly effective treatment. Replacement of trastuzumab by the mimetic peptide favors reduced production costs and technical efforts, and a negligible immune response. Nanodrug trafficking efficacy through tissue and cellular bio-barriers depends on vehicle size and shape. Using slender polymers conjugated with minute targeting molecules and drugs, we boosted delivery to and treatment efficacy of HER2+ breast cancer using a mini nanodrug with a specific mimetic peptide that replaced the HER2+ antibody.
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DOI：
10.1073/pnas.1003919107
发表时间：
2010-10-19
影响因子：
11.1
作者：
Ding, Hui;Inoue, Satoshi;Ljubimova, Julia Y.
通讯作者：
Ljubimova, Julia Y.
DOI：
10.1073/pnas.1509371113
发表时间：
2016-01-19
影响因子：
11.1
作者：
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通讯作者：
Jon, Sangyong
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影响因子：
12.4
作者：
Geng L;Wang Z;Yang X;Li D;Lian W;Xiang Z;Wang W;Bu X;Lai W;Hu Z;Fang Q
通讯作者：
Fang Q
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影响因子：
12.4
作者：
Ding L;Tian C;Feng S;Fida G;Zhang C;Ma Y;Ai G;Achilefu S;Gu Y
通讯作者：
Gu Y
影响因子：
3.3
作者：
Chan, T. C.;Li, H. T.;Li, K. Y.
通讯作者：
Li, K. Y.