期刊
SMALL
卷 18, 期 2, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202104449
关键词
combinatorial therapy; pancreatic cancer; spatiotemporal release; targeted drug delivery
类别
资金
- Thomas Reynolds Graduate Research Award
- National Institute of Cancer of the National Institutes of Health [R15CA192160]
- NIH/NCI [R01CA225637]
A mesoporous silica nanoparticle (MSN)-based platform is developed for the safe and ratiometric co-delivery of Gem and cisplatin (cisPt) in pancreatic ductal adenocarcinoma (PDAC). The nanoparticles demonstrate synergistic therapeutic outcomes in mouse models and show potential for overcoming resistance to Pt-based drugs. Overall, the platform offers a promising approach for targeted therapy in PDAC.
Pancreatic ductal adenocarcinoma (PDAC) is an intractable malignancy with a dismal survival rate. Recent combination therapies have had a major impact on the improvement of PDAC prognosis. Nevertheless, clinically used combination regimens such as FOLFIRINOX and gemcitabine (Gem)/nab-paclitaxel still face major challenges due to lack of the safe and ratiometric delivery of multiple drugs. Here, a rationally designed mesoporous silica nanoparticle (MSN)-based platform is reported for the target-specific, spatiotemporal, ratiometric, and safe co-delivery of Gem and cisplatin (cisPt). It is shown that systemic administration of the nanoparticles results in synergistic therapeutic outcome in a syngeneic and clinically relevant genetically engineered PDAC mouse model that has rarely been used for the therapeutic evaluation of nanomedicine. This synergism is associated with a strategic engineering approach, in which nanoparticles provide redox-responsive controlled delivery and in situ differential release of Gem/cisPt drugs with the goal of overcoming resistance to Pt-based drugs. The platform is also rendered with additional tumor-specificity via a novel tumor-associated mucin1 (tMUC1)-specific antibody, TAB004. Overall, the platform suppresses tumor growth and eliminates the off-target toxicities of a highly toxic chemotherapy combination.
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