التفاصيل البيبلوغرافية
| العنوان: |
Cluster of Differentiation 44 Targeted Hyaluronic Acid Based Nanoparticles for MDR1 siRNA Delivery to Overcome Drug Resistance in Ovarian Cancer. |
| المؤلفون: |
Yang, Xiaoqian, Iyer, Arun, Singh, Amit, Milane, Lara, Choy, Edwin, Hornicek, Francis, Amiji, Mansoor, Duan, Zhenfeng |
| المصدر: |
Pharmaceutical Research; Jun2015, Vol. 32 Issue 6, p2097-2109, 13p, 1 Color Photograph, 5 Graphs |
| مصطلحات موضوعية: |
OVARIAN cancer treatment, HYALURONIC acid, NANOPARTICLES, SMALL interfering RNA, CELL differentiation, DRUG resistance in cancer cells |
| مستخلص: |
Purpose: Approaches for the synthesis of biomaterials to facilitate the delivery of ' biologics' is a major area of research in cancer therapy. Here we designed and characterized a hyaluronic acid (HA) based self-assembling nanoparticles that can target CD44 receptors overexpressed on multidrug resistance (MDR) ovarian cancer. The nanoparticle system is composed of HA-poly(ethyleneimine)/HA-poly(ethylene glycol) (HA-PEI/HA-PEG) designed to deliver MDR1 siRNA for the treatment of MDR in an ovarian cancer model. Methods: HA-PEI/HA-PEG nanoparticles were synthesized and characterized, then the cellular uptake and knockdown efficiency of HA-PEI/HA-PEG/ MDR1 siRNA nanoparticles was further determined. A human xenograft MDR ovarian cancer model was established to evaluate the effects of the combination of HA-PEI/HA-PEG/ MDR1 siRNA nanoparticles and paclitaxel on MDR tumor growth. Results: Our results demonstrated that HA-PEI/HA-PEG nanoparticles successfully targeted CD44 and delivered MDR1 siRNA into OVCAR8TR (established paclitaxel resistant) tumors. Additionally, HA-PEI/HA-PEG nanoparticles loaded with MDR1 siRNA efficiently down-regulated the expression of MDR1 and P-glycoprotein (Pgp), inhibited the functional activity of Pgp, and subsequently increased cell sensitivity to paclitaxel. HA-PEI/HA-PEG/ MDR1 siRNA nanoparticle therapy followed by paclitaxel treatment inhibited tumor growth in MDR ovarian cancer mouse models. Conclusions: These findings suggest that this CD44 targeted HA-PEI/HA-PEG nanoparticle platform may be a clinicaly relevant gene delivery system for systemic siRNA-based anticancer therapeutics for the treatment of MDR cancers. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
