文献：High payload nanoparticles composed of 7-ethyl-10-hydroxycamptothecin and chlorin e6 for synergistic chemo-photodynamic combination therapy

文献链接：https://xueshu.baidu.com/usercenter/paper/show?paperid=1n1q0v30sx580jf0qs6b04v0xt724063&site=xueshu_se

作者：Yanna Zhao, Xinxin Jiang , Qisan Ma , Yuping Zhao , Huaizhen Zhang , Qingpeng Wang ,

Zhuang Ding , Min Liu , Zhengping Wang , Jun Han

相关产品：

DSPE-PEG 磷脂-聚乙二醇

PCL-PEG 聚己内酯-聚乙二醇

Chol–PEG 胆固醇-聚乙二醇

原文摘要：Combined chemo-photodynamic therapy strategy is regarded as a potential strategy for advanced cancer treatments. Herein, novel high payload 7-ethyl-10-hydroxycamptothecin (SN38)/chlorin e6 (Ce6) NPs based on the collaborative assembly of the pre-obtained SN38–Ce6 complex and biocompatible amphiphilic block polymer DSPE-PEG2000 were successfully constructed. The self-assembly mechanism of the NPs was corporately disclosed as static quenching resulted from complex formation between DSPE-PEG2000 and the pre-acquired SN38–Ce6 complex via fluorescence quenching experiment. The high payload SN38/Ce6 NPs exhibited uniform rod-like morphology with a hydrodynamic radius of about 200 nm, a zeta potential of around − 25 mV, and excellent storage stability. The high payload NPs showed efficient singlet oxygen generation capacity both in tube and in murine mammary carcinoma (4T1) cells under laser irradiation. Moreover, the in vitro cytotoxicity and in vivo antitumor efficacy of the NPs (with laser) against 4T1 cell lines model were proved to be statistically significant compared to CPT-11 injection and single-drug NPs due to synergistic

chemo-photodynamictherapy and high cellular uptake efficiency. Meanwhile, the systemic toxicity of the NPs was basically absent.Conclusively, the high payload dual-functional nanoparticles could be served as a promising strategy for cancer treatment in clinic.

该文献基于预先获得的SN38-Ce6复合物和生物相容性嵌段聚合物DSPE-PEG2000的协同组装，构建了有效载荷7-乙基-10-羟基喜树碱（SN38）/氯e6（Ce6）NPs。通过荧光猝灭实验，DSPE-PEG2000与预获得的SN38-Ce6配合物形成配合物后的静态猝灭，共同揭示了NPs的自组装机制。

图：SN38/Ce6 NPs合成示意图及作用机制

SN38/Ce6 NPs的制备

将一定比例的SN38和Ce6在室温下与 N、N-二甲基甲酰胺（DMF）共溶中生成有机相，在连续超声下，滴加入去离子水中。然后，将DSPE-PEG2000、PCL-PEG2000、Chol-PEG2000等两亲性嵌段聚合物分散在DMF中，滴入混合物中。DMF通过透析对去离子水去除，直到没有残留的DMF获得高有效载荷SN38/Ce6 NPs。采用D-3L均质器均质，减少得到的SN38/Ce6 NPs的粒径。

图：在不同浓度的DSPE-PEG2000（1→6： 0、12、24、36、24、36、48和60μM）(A)条件下，SN38-Ce6配合物（SN38： 12 μM和Ce6： 4 μM）的荧光猝灭光谱和猝灭曲线

结论：DSPE-PEG2000、PCL-PEG2000、Chol-PEG2000参与制备的高有效载荷SN38/Ce6 NPs具有均匀的棒状形态，水动力半径约为200nm，zeta电位约为−25 mV，具有良好的存储稳定性。在激光照射下，高有效载荷NPs在试管细胞和小鼠（4T1）细胞中均表现出单线态产氧能力。此外，NPs（使用激光）与CPT-11注射液和单药NPs相比，对4T1细胞系模型的体外细胞有害性和体内抗tumor效果，具有统计学意义。