A platelet-mimetic paradigm for metastasis-targeted nanomedicine platforms.
A platelet-mimetic paradigm for metastasis-targeted nanomedicine platforms.
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DOI：
10.1021/bm301996p
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发表时间：
2013-03-11
影响因子：
6.2
通讯作者：
Sen Gupta, Anirban
中科院分区：
文献类型：
--
作者：
Modery-Pawlowski, Christa L.;Master, Alyssa M.;Pan, Victor;Howard, Gregory P.;Sen Gupta, Anirban
有令人信服的证据表明，血小板除了在止血和血栓形成方面的传统作用外，还通过与促转移癌细胞直接和间接相互作用，在介导肿瘤转移的血液学机制中发挥重要作用。基于这一原理，我们假设血小板可成为开发纳米医学平台的有效范例，该平台利用血小板模拟相互作用机制对转移性癌细胞进行靶向诊断和治疗。在此我们报道了我们对通过血小板模拟多价异源配体 - 受体途径与转移性癌细胞相互作用的纳米构建体开发的研究。在我们的研究中，对促转移的人乳腺癌细胞系MDA - MB - 231与另一种低转移的人乳腺癌细胞系MCF - 7相比，研究了其血小板相互作用受体的表面表达。发现某些血小板相互作用受体在MDA - MB - 231细胞上显著过度表达，并且与MCF - 7细胞相比，这些细胞与活性血小板的结合相互作用显著增强。基于这些观察结果，选择了两种特定的受体相互作用，并将相应的配体设计到脂质体表面作为模型纳米构建体，以实现与癌细胞的血小板模拟结合。与MCF - 7细胞相比，我们的模型血小板模拟脂质体构建体对MDA - MB - 231细胞显示出更强的靶向性和附着性。这些结果表明利用血小板模拟构建体改造用于转移靶向药物的纳米载体构建体以及改造用于体外细胞富集诊断技术的表面是有前景的。
There is compelling evidence that beyond their traditional role in hemostasis and thrombosis, platelets play a significant role in mediating hematologic mechanisms of tumor metastasis by directly and indirectly interacting with pro-metastatic cancer cells. With this rationale, we hypothesized that platelets can be an effective paradigm to develop nanomedicine platforms that utilize platelet-mimetic interaction mechanisms for targeted diagnosis and therapy of metastatic cancer cells. Here we report on our investigation of the development of nanoconstructs that interact with metastatic cancer cells via platelet-mimetic heteromultivalent ligand-receptor pathways. For our studies, pro-metastatic human breast cancer cell line MDA-MB-231 was studied for its surface expression of platelet-interactive receptors, in comparison to another low-metastatic human breast cancer cell line, MCF-7. Certain platelet-interactive receptors were found to be significantly over-expressed on the MDA-MB-231 cells and these cells showed significantly enhanced binding interactions with active platelets compared to MCF-7 cells. Based upon these observations, two specific receptor interactions were selected and corresponding ligands were engineered onto the surface of liposomes as model nanoconstructs, to enable platelet-mimetic binding to the cancer cells. Our model platelet-mimetic liposomal constructs showed enhanced targeting and attachment of MDA-MB-231 cells compared to the MCF-7 cells. These results demonstrate the promise of utilizing platelet-mimetic constructs in modifying nanovehicle constructs for metastasis-targeted drug as well as modifying surfaces for ex-vivo cell enrichment diagnostic technologies.
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影响因子：
14
作者：
Eniola, AO;Hammer, DA
通讯作者：
Hammer, DA
DOI：
10.1093/jnci/53.3.661
发表时间：
1974-01-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
CAILLEAU, R;YOUNG, R;REEVES, WJ
通讯作者：
REEVES, WJ
影响因子：
--
作者：
Bendas G;Borsig L
通讯作者：
Borsig L
影响因子：
6.7
作者：
Gerges, Noha;Rak, Janusz;Jabado, Nada
通讯作者：
Jabado, Nada
DOI：
10.1073/pnas.61.1.46
发表时间：
1968-01-01
影响因子：
11.1
作者：
GASIC, GJ;GASIC, TB;STEWART, CC
通讯作者：
STEWART, CC