Peptide-Conjugated PAMAM for Targeted Doxorubicin Delivery to Transferrin Receptor Overexpressed Tumors
Peptide-Conjugated PAMAM for Targeted Doxorubicin Delivery to Transferrin Receptor Overexpressed Tumors
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肽缀合的 PAMAM 用于靶向阿霉素递送至转铁蛋白受体过度表达的肿瘤
DOI：
10.1021/mp100185f
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发表时间：
2010-11-01
影响因子：
4.9
通讯作者：
Jiang, Chen
中科院分区：
文献类型：
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作者：
Han, Liang;Huang, Rongqin;Jiang, Chen
这项工作的目的是评估HAIYPRH(T7)肽作为配体构建肿瘤靶向药物传递系统的潜力。T7可通过转铁蛋白受体(TFR)表面的空腔靶向转铁蛋白受体(TFR)，然后在转铁蛋白(Tf)的帮助下通过内吞作用进入细胞内。本研究成功地合成了T7-聚乙二醇改性聚酰胺胺树状大分子(PAMAM-PEG-T7)，并进一步负载阿霉素(DOX)，制备了PAMAM-PEG-T7/DOX纳米粒(NPs)。在体外，在pH 5.5条件下，DOX在2 h内几乎100%被释放，而在pH 7.4条件下，在48 h内只有55%的DOX被释放。当T7修饰的纳米粒在Tf存在的情况下处理时，细胞对DOX的摄取显著增加。体外抗肿瘤作用明显增强。添加转铁蛋白的PAMAM-PEGT7/DOX纳米粒的IC50值为231.5 nm，而不加转铁蛋白的纳米粒的IC50为676.7 nM。T7修饰的纳米粒可显著增加DOX在肿瘤中的蓄积，与未修饰的纳米粒相比，增加约1.7倍，与游离的多柔比星相比，增加约5.3倍。在体内抗肿瘤研究中，与PAMAM-PEG/DOX纳米粒和生理盐水治疗组相比，PAMAM-PEG-T7/DOX纳米粒组小鼠的肿瘤生长受到显著抑制。本研究为PAMAM-PEG-T7作为一种潜在的肿瘤靶向给药系统提供了证据。T7可能是一种很有前途的靶向给药的配体。
The purpose of this work was to evaluate the potential of HAIYPRH (T7) peptide as a ligand for constructing tumor-targeting drug delivery systems. T7 could target to transferrin-receptor (TfR) through a cavity on the surface of TfR and then transport into cells via endocytosis with the help of transferrin (Tf). In this study, T7-conjugated poly(ethylene glycol) (PEG)-modified polyamidoamine dendrimer (PAMAM) (PAMAM-PEG-T7) was successfully synthesized and further loaded with doxorubicin (DOX), formulating PAMAM-PEG-T7/DOX nanoparticles (NPs). In vitro, almost 100% of DOX was released during 2 h in pH 5.5, while only 55% of DOX was released over 48 h in pH 7.4. The cellular uptake of DOX could be significantly enhanced when treated with T7-modified NPs in the presence of Tf. Also, the in vitro antitumor effect was enhanced markedly. The IC50 of PAMAM-PEG-T7/DOX NPs with Tf was 231.5 nM, while that of NPs without Tf was 676.7 nM. T7-modified NPs could significantly enhance DOX accumulation in the tumor by approximately 1.7-fold compared to that of unmodified ones and by approximately 5.3-fold compared to that of free DOX. For in vivo antitumor studies, tumor growth of mice treated with PAMAM-PEG-T7/DOX NPs was significantly inhibited compared to that of mice treated with PAMAM-PEG/DOX NPs and saline. The study provides evidence that PAMAM-PEG-T7 can be applied as a potential tumor-targeting drug delivery system. T7 may be a promising ligand for targeted drug delivery to the tumor.