期刊
THERANOSTICS
卷 6, 期 12, 页码 2250-2266出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.15710
关键词
oral administration; combination therapy; mucosal protection; anti-inflammation; targeted nanoparticle; ulcerative colitis
资金
- Department of Veterans Affairs [BX002526]
- National Institutes of Health of Diabetes and Digestive and Kidney [RO1-DK-071594]
- Crohn's and Colitis Foundation of America
- National Natural Science Foundation of China [51503172, 81571807]
- Fundamental Research Funds for the Central Universities [SWU114086, XDJK2015C067]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars (State Education Ministry)
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK071594] Funding Source: NIH RePORTER
- Veterans Affairs [I01BX002526] Funding Source: NIH RePORTER
Combination therapy is an emerging strategy that is under intensive preclinical investigation for the treatment of various diseases. CD98 is highly overexpressed on the surfaces of epithelial cells and macrophages in the colon tissue with ulcerative colitis (UC), which is usually associated with mucosal damage and inflammation. We previously proved that CD98 siRNA (siCD98)-induced down-regulation of CD98 in colitis tissue decreased the severity of UC to a certain extent. In an effort to further improve the therapeutic efficacy, we aim to simultaneously deliver siCD98 in combination with a potent anti-inflammatory agent, curcumin (CUR), using hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant spherical HA-siCD98/ CUR-NPs are featured by a desirable particle size (similar to 246 nm) and slightly negative zeta potential (similar to-14 mV). The NPs functionalized with HA are able to guide the co-delivery of drugs to the targeted cells related to UC therapy (colonic epithelial cells and macrophages). Compared to either siCD98-or CUR-based monotherapy, co-delivery of siCD98 and CUR by HA-functionalized NPs can exert combinational effects against UC by protecting the mucosal layer and alleviating inflammation both in vitro and in vivo. This study shows the promising capability of the co-delivered siCD98 and CUR for boosting the conventional monotherapy via this novel nanotherapeutic agent, which offers a structurally simple platform for orally administered delivery of drugs to target cells in UC therapy.
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