右旋糖酐
化学
顺铂
全身给药
结直肠癌
癌症研究
药物输送
口服
体内
药理学
生物物理学
癌症
材料科学
纳米技术
生物化学
医学
化疗
生物
外科
生物技术
内科学
作者
I-Lin Lu,Ting-Wei Yu,Te-I Liu,Hsin-Hung Chen,Ying Yang,Chun Liang Lo,Chi-Ya Wang,Hsin‐Cheng Chiu
标识
DOI:10.1002/adhm.202201140
摘要
Multifunctional sequential targeted delivery system is developed as an efficient therapeutic strategy against malignant tumors with selective accumulation and minimal systemic drug absorption. The therapeutic system is comprised of microfluidized dextran microgels encapsulating cisplatin/superparamagnetic iron oxide nanoparticles (SPIONs)-loaded trilaurin-based lipid nanoparticles (LNPs). The microgel system is imparted hierarchically dual targeting via dextran and folic acid (FA) residues, leading to increases both in retention of the microgels in colon and in cellular uptake of the therapeutic LNPs by colon cancer cells while being used for oral therapeutic delivery. Encapsulation of the therapeutic LNPs into dextran microgels attained by microfluidized crosslinking reaction reduces gastrointestinal adhesion and prevents the FA-modified LNPs from cellular transport by proton-coupled FA transporters in small intestine during their oral delivery to colon. Upon enzymatic degradation of the dextran microgels by dextranase present exclusively in colon, LNPs thus released become more recognizable and readily internalized by FA receptor-overexpressing colon cancer cells. The combined chemo/magnetothermal therapeutic effect of dual targeted lipid nanoparticle-loaded microgels from entrapped lipidized cisplatin and alternating magnetic field-treated SPIONs significantly inhibits tumor growth and suppresses metastatic peritoneal carcinomatosis in orthotopic colon cancer-bearing mice.
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