Intracellular tracking of drug release from pH-sensitive polymeric nanoparticles via FRET for synergistic chemo-photodynamic therapy
Intracellular tracking of drug release from pH-sensitive polymeric nanoparticles via FRET for synergistic chemo-photodynamic therapy
复制标题
通过 FRET 追踪 pH 敏感聚合物纳米颗粒的药物释放，用于协同化学光动力治疗
DOI：
10.1186/s12951-019-0547-2
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发表时间：
2019-11-07
影响因子：
10.2
通讯作者：
Sun, Yong
中科院分区：
文献类型：
--
作者：
Du, Chen;Liang, Yan;Sun, Yong
背景肿瘤协同治疗是一种很有前途的治疗肿瘤的方法，其目的是实现实时药物释放监测、动态细胞成像和抗肿瘤活性的有效肿瘤治疗。合成了一种两亲性聚合物环（RGDfCSH）（cRGD）-聚乙二醇（PEG）-聚组氨酸（PH）-聚己内酯（PCL）-原卟啉（Por）-，该聚合物既可作为光敏剂用于光动力学治疗（PDT），又可在FRET中吸收受体。制备的纳米粒平均粒径为150 ± 2.4 nm，表面带负电，pH敏感，载药量高（14.9 ± 1.5%）。通过EPI和cRGD-PEG-PH-PCL-Por之间的FRET效应，真实的监测负载EPI的cRGD-PEG-PH-PCL-Por的细胞摄取。聚合物纳米粒子结合PDT和化疗显示出显着的抗癌活性在体外（IC 50 = 0.47 μg/mL）和更好的治疗效果比游离EPI在vivo.ConclusionsThis工作提供了一个通用的策略，以制造纳米组装体的细胞内跟踪药物释放和协同化学-光动力学治疗。
BackgroundSynergistic therapy of tumor is a promising way in curing cancer and in order to achieve effective tumor therapy with real-time drug release monitoring, dynamic cellular imaging and antitumor activity.ResultsIn this work, a polymeric nanoparticle with Forster resonance energy transfer (FRET) effect and chemo-photodynamic properties was fabricated as the drug vehicle. An amphiphilic polymer of cyclo(RGDfCSH) (cRGD)-poly(ethylene glycol) (PEG)-Poly(l-histidine) (PH)-poly(ε-caprolactone) (PCL)-Protoporphyrin (Por)-acting as both a photosensitizer for photodynamic therapy (PDT) and absorption of acceptor in FRET was synthesized and self-assembled into polymeric nanoparticles with epirubicin (EPI)-acting as an antitumor drug for chemotherapy and fluorescence of donor in FRET. Spherical EPI-loaded nanoparticles with the average size of 150 ± 2.4 nm was procured with negatively charged surface, pH sensitivity and high drug loading content (14.9 ± 1.5%). The cellular uptake of EPI-loaded cRGD-PEG-PH-PCL-Por was monitored in real time by the FRET effect between EPI and cRGD-PEG-PH-PCL-Por. The polymeric nanoparticles combined PDT and chemotherapy showed significant anticancer activity both in vitro (IC50= 0.47 μg/mL) and better therapeutic efficacy than that of free EPI in vivo.ConclusionsThis work provided a versatile strategy to fabricate nanoassemblies for intracellular tracking of drug release and synergistic chemo-photodynamic therapy.