Polyhedral Oligomeric Silsesquioxanes-Containing Conjugated Polymer Loaded PLGA Nanoparticles with Trastuzumab (Herceptin) Functionalization for HER2-Positive Cancer Cell Detection
Polyhedral Oligomeric Silsesquioxanes-Containing Conjugated Polymer Loaded PLGA Nanoparticles with Trastuzumab (Herceptin) Functionalization for HER2-Positive Cancer Cell Detection
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DOI：
10.1002/adfm.201001435
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发表时间：
2011-01-21
影响因子：
19
通讯作者：
Liu, Bin
中科院分区：
文献类型：
--
作者：
Li, Kai;Liu, Yutao;Liu, Bin
报道了含多面体低聚倍半硅氧烷（POSS）的共轭聚合物（CP）和表面抗体功能化的聚合物负载的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒（NPs）的合成，用于人表皮生长因子受体2（HER 2）阳性癌细胞的检测。由于POSS的空间位阻，与相应的线性CP封装的NP相比，由含POSS的CP制备的NP显示出改善的光致发光量子产率。此外，通过在NP配制过程中改变聚（乳酸-共-乙醇酸）-b-聚（乙二醇）（PLGA-b-PEG-NH 2）与PLGA-OCH 3的摩尔比，可以很好地控制NP表面上-NH 2基团的量。NH 2-官能化的CP NP与曲妥珠单抗（赫赛汀）的进一步缀合产生具有微调的蛋白质密度的NP。这些NP能够通过利用曲妥珠单抗与SKBR-3乳腺癌细胞膜中过表达的HER 2之间的特异性结合亲和力，在基底上和悬浮液中区分SKBR-3乳腺癌细胞与MCF-7乳腺癌细胞和NIH/3 T3成纤维细胞。高量子产率和微调的表面特异性蛋白质功能化使得含有POSS的CP负载的NP成为靶向生物成像和检测的良好候选物。
The synthesis of polyhedral oligomeric silsesquioxanes (POSS)-containing conjugated polymer (CP) and the polymer loaded poly(lactic-co-glycolic-acid) (PLGA) nanoparticles (NPs) with surface antibody functionalization for human epidermal growth factor receptor 2 (HER2)-positive cancer cell detection are reported. Due to the steric hindrance of POSS, NPs prepared from POSS-containing CP show improved photoluminescence quantum yield as compared to that for the corresponding linear CP encapsulated NPs. In addition, the amount of -NH2 groups on NP surface is well-controlled by changing the molar ratio of poly(lactic-co-glycolic-acid)-b-poly(ethylene glycol) (PLGA-b-PEG-NH2) to PLGA-OCH3 during NP formulation. Further conjugation of the NH2-functionalized CP NPs with trastuzumab (Herceptin) yields NPs with fine-tuned protein density. These NPs are able to discriminate SKBR-3 breast cancer cells from MCF-7 breast cancer cells and NIH/3T3 fibroblast cells both on substrate and in suspension by taking advantage of the specific binding affinity between trastuzumab and HER2 overexpressed in SKBR-3 breast cancer cell membrane. The high quantum yield and fine-tuned surface specific protein functionalization make the POSS-containing CP loaded NPs a good candidate for targeted biological imaging and detection.