Herein, a mesoporous silica nanoparticle (MSN) based biocompatible, targeted and controlled drug delivery system has been synthesized for tumor tissue-specific drug delivery. Umbelliferone, a natural coumarin derivative was loaded into the pores of MSN and capped with pH-sensitive poly acrylic acid (PAA). For targeted delivery of umbelliferone in tumor tissue, folic acid (FA) was grafted onto the surface of drug-loaded and PAA-coated MSN. The successful construction of the nanohybrid (Umbe@MSN-PAA-FA) was confirmed by performing a series of characterization. The synthesized pH-responsive nanohybrid showed diameter of around 50 nm with overall negative surface charge and drug loading content of 12.56%. In vitro study showed that the nanohybrid caused significant cytotoxicity through the induction of both oxidative stress as well as mitochondrial damage in folate receptor over-expressed in human breast cancer cell, MCF-7 compared with free umbelliferone. In vivo study also exhibited that the nanohybrid effectively reduced tumor growth in tumor-bearing mice compared with free umbelliferone due to the enlarged bioavailability of the drug in tumor tissue. Besides, the nanohybrid did not exhibit any significant sign of systemic toxicity in other vital organs. Together, the study denoted that PAA and FA functionalized MSN controlled-drug delivery system could assist to increase the anticancer potential of umbelliferone.

本文中，已经合成了基于介孔二氧化硅纳米颗粒（MSN）的生物相容性，靶向性和受控的药物递送系统，用于肿瘤组织特异性药物递送。将天然香豆素衍生物Umbelliferone装入MSN的孔中，并用pH敏感的聚丙烯酸（PAA）封端。为了在肿瘤组织中靶向递送伞形酮，将叶酸（FA）嫁接到载有药物并涂有PAA的MSN表面。通过进行一系列表征，证实了纳米杂交体（Umbe @ MSN-PAA-FA）的成功构建。合成的pH响应纳米杂化物显示出约50 nm的直径，总负表面电荷和载药量为12.56％。体外研究表明，与游离伞形酮相比，纳米杂交体通过诱导人乳腺癌细胞MCF-7中过量表达的叶酸受体的氧化应激以及线粒体损伤，引起了显着的细胞毒性。体内研究还显示，由于该药物在肿瘤组织中的生物利用度提高，因此与游离伞形酮相比，该纳米杂合物有效地降低了荷瘤小鼠的肿瘤生长。此外，纳米杂化物在其他重要器官中没有表现出任何明显的全身毒性迹象。总之，该研究表明，PAA和FA功能化的MSN受控药物递送系统可以帮助增加伞形酮的抗癌潜力。体内研究还显示，由于该药物在肿瘤组织中的生物利用度提高，因此与游离伞形酮相比，该纳米杂合物有效地降低了荷瘤小鼠的肿瘤生长。此外，纳米杂化物在其他重要器官中没有表现出任何明显的全身毒性迹象。总之，该研究表明，PAA和FA功能化的MSN受控药物递送系统可以帮助增加伞形酮的抗癌潜力。体内研究还显示，由于该药物在肿瘤组织中的生物利用度提高，因此与游离伞形酮相比，该纳米杂合物有效地降低了荷瘤小鼠的肿瘤生长。此外，纳米杂化物在其他重要器官中没有表现出任何明显的全身毒性迹象。总之，该研究表明，PAA和FA功能化的MSN受控药物递送系统可以帮助增加伞形酮的抗癌潜力。