Transferrin-Conjugated Polymeric Nanoparticle for Receptor-Mediated Delivery of Doxorubicin in Doxorubicin-Resistant Breast Cancer Cells
Transferrin-Conjugated Polymeric Nanoparticle for Receptor-Mediated Delivery of Doxorubicin in Doxorubicin-Resistant Breast Cancer Cells
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DOI：
10.3390/pharmaceutics11020063
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发表时间：
2019-02-01
期刊：
影响因子：
5.4
通讯作者：
Kim, Jong Oh
中科院分区：
文献类型：
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作者：
Soe, Zar Chi;Kwon, Jun Bum;Kim, Jong Oh
在这项研究中，转铁蛋白（T-f）-共轭聚合物纳米粒子的化疗药物阿霉素（Dox），以克服癌症治疗中的多药耐药性的目标交付。我们的目标是改善Dox递送，以在对健康细胞具有最小毒性的Dox抗性（R）乳腺癌细胞系中产生显著的抗肿瘤功效。我们的实验结果表明，Dox成功地装载在由泊洛沙姆407（F127）和123（P123）组成的转铁蛋白（T-f）缀合的聚合物纳米颗粒（Dox/F127和P123-T-f）内，其产生具有低多分散指数（类似于0.23）的纳米尺寸的颗粒（类似于90 nm）。在酸性和生理pH下表征了Dox从纳米颗粒的加速和控制释放曲线，并且Dox/F127和P123-T-f通过诱导细胞凋亡增强了OVCAR-3、MDA-MB-231和MDA-MB-231（R）细胞系中的Dox细胞毒性。此外，Dox/F127和P123-T-f抑制细胞迁移并改变不同癌细胞的细胞周期模式。在MDA-MB-231（R）荷瘤小鼠中的体内研究表明，当涂覆靶向部分时，纳米颗粒向肿瘤部位的递送增强。因此，Dox/F127和P123-T-f已经使用纳米治疗的原理进行了定制，以克服耐药性化疗。
In this study, a transferrin (T-f)-conjugated polymeric nanoparticle was developed for the targeted delivery of the chemotherapeutic agent doxorubicin (Dox) in order to overcome multi-drug resistance in cancer treatment. Our objective was to improve Dox delivery for producing significant antitumor efficacy in Dox-resistant (R) breast cancer cell lines with minimum toxicity to healthy cells. The results of our experiments revealed that Dox was successfully loaded inside a transferrin (T-f)-conjugated polymeric nanoparticle composed of poloxamer 407 (F127) and 123 (P123) (Dox/F127&P123-T-f), which produced nanosized particles (similar to 90 nm) with a low polydispersity index (similar to 0.23). The accelerated and controlled release profiles of Dox from the nanoparticles were characterized in acidic and physiological pH and Dox/F127&P123-T-f enhanced Dox cytotoxicity in OVCAR-3, MDA-MB-231, and MDA-MB-231(R) cell lines through induction of cellular apoptosis. Moreover, Dox/F127&P123-T-f inhibited cell migration and altered the cell cycle patterns of different cancer cells. In vivo study in MDA-MB-231(R) tumor-bearing mice demonstrated enhanced delivery of nanoparticles to the tumor site when coated in a targeting moiety. Therefore, Dox/F127&P123-T-f has been tailored, using the principles of nanotherapeutics, to overcome drug-resistant chemotherapy.