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Noninvasive Preclinical Evaluation of Targeted Nanoparticles for the Delivery of Curcumin in Treating Pancreatic Cancer
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-06-09 , DOI: 10.1021/acsabm.0c00515 Prabhuraj R S 1 , Arijit Mal 2 , Snehal K Valvi 2 , Rohit Srivastava 3 , Abhijit De 2 , Rajdip Bandyopadhyaya 4
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-06-09 , DOI: 10.1021/acsabm.0c00515 Prabhuraj R S 1 , Arijit Mal 2 , Snehal K Valvi 2 , Rohit Srivastava 3 , Abhijit De 2 , Rajdip Bandyopadhyaya 4
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Conventional therapy regimens for pancreatic cancer (PC) are surgical resection and systemic gemcitabine based chemotherapy. Recent studies showed that curcumin could potentiate the anticancer effect of gemcitabine in PC. However, due to its poor water solubility, effective bioavailability of curcumin is insufficient, resulting in poor efficacy. To address this issue, mesoporous silica nanoparticles (MSN) were prepared by the sol–gel method, then loaded with curcumin (Cur), coated with polyethylene glycol (PEG), and finally conjugated with the targeting moiety transferrin (Tf) to target human PC cells. TEM analysis revealed that uniform sized spherical MSN formed with an average size of 100 nm, which increased to 120 nm after PEG coating on MSN surface. Confocal microscopy proved that curcumin uptake being seven-times higher for MSN–NH2–Cur–PEG–Tf, when compared to free curcumin. The in vitro cytotoxicity study on MIA PaCa-2 cells showed that MSN–NH2–Cur–PEG–Tf exhibited three-fold higher cytotoxicity than free curcumin. On the basis of the encouraging in vitro cytotoxicity results obtained, preclinical assessment of antitumor efficacy in MIA PaCa-2 subcutaneous xenograft model proves that both MSN–NH2–Cur–PEG and MSN–NH2–Cur–PEG–Tf inhibit tumor growth and minimize distant metastasis to major organ sites. The in vitro studies also proved that nanoparticles can enhance the sensitization effect, caused by curcumin on cancer cells, which help the gemcitabine to kill a higher percentage of cancer cells. Hence, we propose that transferrin targeted, PEGylated, mesoporous silica nanoparticles can be used as a carrier to deliver curcumin, and used in addition to gemcitabine to reduce disease burden significantly for pancreatic cancer patients.
中文翻译：
靶向纳米颗粒递送姜黄素治疗胰腺癌的无创临床前评价
胰腺癌 (PC) 的常规治疗方案是手术切除和全身性吉西他滨化疗。最近的研究表明，姜黄素可以增强吉西他滨在 PC 中的抗癌作用。但由于其水溶性差，姜黄素的有效生物利用度不足，导致疗效不佳。为了解决这个问题，通过溶胶-凝胶法制备介孔二氧化硅纳米粒子（MSN），然后负载姜黄素（Cur），涂上聚乙二醇（PEG），最后与靶向部分转铁蛋白（Tf）缀合以靶向人个人电脑细胞。TEM分析表明，形成了均匀尺寸的球形MSN，平均尺寸为100 nm，在MSN表面涂上PEG后增加到120 nm。共聚焦显微镜证明 MSN-NH 的姜黄素摄取量高出 7 倍2 –Cur–PEG–Tf，与游离姜黄素相比。MIA PaCa-2 细胞的体外细胞毒性研究表明，MSN-NH 2 -Cur-PEG-Tf 的细胞毒性是游离姜黄素的三倍。在获得令人鼓舞的体外细胞毒性结果的基础上，MIA PaCa-2 皮下异种移植模型中抗肿瘤功效的临床前评估证明 MSN-NH 2 -Cur-PEG 和 MSN-NH 2 -Cur-PEG-Tf 均能抑制肿瘤生长并尽量减少向主要器官部位的远处转移。体外的研究还证明，纳米颗粒可以增强姜黄素对癌细胞的致敏作用，这有助于吉西他滨杀死更高比例的癌细胞。因此，我们建议转铁蛋白靶向、聚乙二醇化、介孔二氧化硅纳米粒子可用作递送姜黄素的载体，并与吉西他滨一起使用，以显着减轻胰腺癌患者的疾病负担。
更新日期：2020-07-20
中文翻译：
靶向纳米颗粒递送姜黄素治疗胰腺癌的无创临床前评价
胰腺癌 (PC) 的常规治疗方案是手术切除和全身性吉西他滨化疗。最近的研究表明，姜黄素可以增强吉西他滨在 PC 中的抗癌作用。但由于其水溶性差，姜黄素的有效生物利用度不足，导致疗效不佳。为了解决这个问题，通过溶胶-凝胶法制备介孔二氧化硅纳米粒子（MSN），然后负载姜黄素（Cur），涂上聚乙二醇（PEG），最后与靶向部分转铁蛋白（Tf）缀合以靶向人个人电脑细胞。TEM分析表明，形成了均匀尺寸的球形MSN，平均尺寸为100 nm，在MSN表面涂上PEG后增加到120 nm。共聚焦显微镜证明 MSN-NH 的姜黄素摄取量高出 7 倍2 –Cur–PEG–Tf，与游离姜黄素相比。MIA PaCa-2 细胞的体外细胞毒性研究表明，MSN-NH 2 -Cur-PEG-Tf 的细胞毒性是游离姜黄素的三倍。在获得令人鼓舞的体外细胞毒性结果的基础上，MIA PaCa-2 皮下异种移植模型中抗肿瘤功效的临床前评估证明 MSN-NH 2 -Cur-PEG 和 MSN-NH 2 -Cur-PEG-Tf 均能抑制肿瘤生长并尽量减少向主要器官部位的远处转移。体外的研究还证明，纳米颗粒可以增强姜黄素对癌细胞的致敏作用，这有助于吉西他滨杀死更高比例的癌细胞。因此，我们建议转铁蛋白靶向、聚乙二醇化、介孔二氧化硅纳米粒子可用作递送姜黄素的载体，并与吉西他滨一起使用，以显着减轻胰腺癌患者的疾病负担。
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