Institute for NanoScale Science and Technology, College of Science and Engineering, Flinders University, Tonsley, SA 5042, Australia.
Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia.
Biosensors (Basel). 2022 May 29;12(6):373. doi: 10.3390/bios12060373.
In this study, a brush-like polymer with aggregation-induced emission (AIE) features was synthesized for drug delivery and intracellular drug tracking. The polymer consisting of tetraphenylethene (TPE) chain-end as well as oligo-poly (ethylene glycol) (PEG) and hydrazine functionalities was successfully synthesized through copper (0)-mediated reversible-deactivation radical polymerization (Cu-mediated RDRP). Anticancer drug doxorubicin (DOX) was conjugated to the polymer and formed a prodrug named TPE-PEGA-Hyd-DOX, which contains 11% DOX. The hydrazone between DOX and polymer backbone is a pH-sensitive linkage that can control the release of DOX in slightly acidic conditions, which can precisely control the DOX release rate. The drug release of 10% after 96 h in normal cell environments compared with about 40% after 24 h in cancer cell environments confirmed the influence of the hydrazone bond. The ratiometric design of fluorescent intensities with peaks at 410 nm (emission due to AIE feature of TPE) and 600 nm (emission due to ACQ feature of DOX) provides an excellent opportunity for this product as a precise intracellular drug tracker. Cancer cells confocal microscopy showed negligible DOX solution uptake, but an intense green emission originated from prodrug uptake. Moreover, a severe red emission in the DOX channel confirmed a promising level of drug release from the prodrug in the cytoplasm. The merged images of cancer cells confirmed the high performance of the TPE-PEGA-Hyd-DOX compound in the viewpoints of cellular uptake and drug release. This polymer prodrug successfully demonstrates low cytotoxicity in healthy cells and high performance in killing cancer cells.
在这项研究中，合成了一种具有聚集诱导发光（AIE）特性的刷状聚合物，用于药物传递和细胞内药物跟踪。该聚合物由四苯乙烯（TPE）链端以及聚（乙二醇）（PEG）和肼官能团组成，通过铜（0）介导的可逆失活自由基聚合（Cu 介导的 RDRP）成功合成。将抗癌药物阿霉素（DOX）连接到聚合物上，形成一种前药，命名为 TPE-PEGA-Hyd-DOX，其中包含 11%的 DOX。DOX 与聚合物主链之间的腙键是一种 pH 敏感的键，可以控制 DOX 在微酸性条件下的释放，从而可以精确控制 DOX 的释放速度。在正常细胞环境中，10%的药物在 96 小时后释放，而在癌细胞环境中，24 小时后约有 40%的药物释放，这证实了腙键的影响。在 410nm（由于 TPE 的 AIE 特性而发射）和 600nm（由于 DOX 的 ACQ 特性而发射）处荧光强度的比色设计为该产品作为精确的细胞内药物追踪器提供了极好的机会。癌细胞共聚焦显微镜显示 DOX 溶液摄取量可忽略不计，但源于前药摄取的强烈绿色发射。此外，DOX 通道中严重的红色发射证实了前药在细胞质中具有有前途的药物释放水平。癌细胞的合并图像证实了 TPE-PEGA-Hyd-DOX 化合物在细胞摄取和药物释放方面的高性能。该聚合物前药在健康细胞中表现出低细胞毒性，在杀死癌细胞方面表现出高性能。
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