Department of Chinese Medicine Pharmacology, School of Traditional Chinese Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Int J Nanomedicine. 2020 Jan 21;15:433-444. doi: 10.2147/IJN.S229154. eCollection 2020.
Carbon dots (CDs) have attracted extensive attention in recent years because of their high biocompatibility and unique optical property. But they could not be well applied in the drug delivery system to enable distribution in tumor sites with their low pH sensitivity. They are barriers for drug delivery. CDs as an imaging proper were conjugated with doxorubicin (DOX) lipid-coated calcium phosphate (LCP) nanoparticle, for a pH-sensitive nanocarrier and delivery of the antitumor drugs.
CDs were prepared by one-step hydrothermal treatment of citric acid and ethylenediamine. The nanoparticles were simply prepared by using microemulsion technology to form calcium phosphate (CaP) core and further coated with cationic lipids.
The structure was characterized by FTIR, XRD and TEM. In vitro release study revealed that DOX-CDs@LCP was pH dependent. The cytotoxicity assay demonstrated that it exhibited enhanced efficiency compared to the control group (DOX-CDs), but weaker than free DOX. The cellular uptake revealed that these pH-sensitive nanoparticles could be taken up effectively and deliver DOX into the cytoplasm to reach antitumor effect. The fluorescence imaging indicated that DOX-CDs@LCP mostly distributed in the tumor region due to the enhanced permeability and retention effect (EPR) to reduce its systematical toxicity. Importantly, an antitumor activity study demonstrated that the DOX-CDs@LCP nanoparticles had higher antitumor activity than any other groups and lower toxicity. The results showed that LCP could significantly promote the release in tumor microenvironment due to pH-response. The DOX-CDs could enhance load capacity and reduce drug premature releasing; real-time tracking of efficacy as confocal imaging contrast agent. Thus, DOX-CDs@LCP had antitumor capacity and lower systematic toxicity in tumor therapy.
DOX-CDs@LCP were proven as a promising tumor pH-sensitive and imaging-guided drug delivery system for liver cancer chemotherapy.
近年来，由于其高生物相容性和独特的光学特性，碳点（CDs）引起了广泛的关注。但由于其对低 pH 值的敏感性低，它们不能很好地应用于药物传递系统，以使其分布在肿瘤部位。这是药物传递的障碍。将作为成像剂的 CDs 与阿霉素（DOX）脂质包覆的磷酸钙（LCP）纳米颗粒缀合，制成 pH 敏感的纳米载体并递送抗肿瘤药物。
通过一步水热处理柠檬酸和乙二胺制备 CDs。通过微乳液技术简单制备纳米颗粒，形成磷酸钙（CaP）核，进一步用阳离子脂质包覆。
采用傅里叶变换红外光谱（FTIR）、X 射线衍射（XRD）和透射电子显微镜（TEM）对结构进行了表征。体外释放研究表明，DOX-CDs@LCP 呈 pH 依赖性。细胞毒性试验表明，与对照组（DOX-CDs）相比，它表现出增强的效率，但比游离 DOX 弱。细胞摄取表明这些 pH 敏感的纳米颗粒可以有效地摄取并将 DOX 递送到细胞质中以达到抗肿瘤作用。荧光成像表明，由于增强的通透性和保留效应（EPR），DOX-CDs@LCP 主要分布在肿瘤区域，以降低其系统毒性。重要的是，抗肿瘤活性研究表明，DOX-CDs@LCP 纳米颗粒的抗肿瘤活性高于其他组，毒性较低。结果表明，由于 pH 响应，LCP 可以显著促进肿瘤微环境中的释放。DOX-CDs 可以增强载药量并减少药物过早释放；作为共聚焦成像对比剂进行疗效的实时跟踪。因此，DOX-CDs@LCP 在肿瘤治疗中具有抗肿瘤能力和较低的系统毒性。
DOX-CDs@LCP 被证明是一种有前途的肝癌化疗 pH 敏感和成像引导的药物传递系统。
