Murine orthotopic models, utilising female athymic nude mice, were injected with SKOV3Trip2 taxane-resistant ovarian cancer cell line and consequently,
following one week, subjected to anti-Jagged1 siRNA/chitosan Nintedanib side effects nanoparticle complexes (5μg dose of siRNA) with/without taxane, applied via intraperitoneal route twice weekly for a total period Inhibitors,research,lifescience,medical of five weeks . The results of this study indicated that such nanoparticle-based complexes had the capacity to reduce tumour weight by over 70% within such murine models and also induced taxane sensitization within the tumour . In a similar study, cationic liposome-polycation-DNA (LPD) and anionic liposome-polycation-DNA (LPD II) nanoparticle systems were developed to incorporate doxorubicin and VEGF siRNA within a murine ovarian cancer animal model . Female, athymic nude Inhibitors,research,lifescience,medical mice were treated with 5 × 106
cells of the MDR ovarian cancer cell line NCI/ADR-RES . Once the murine tumours reached a size of approximately 16–25mm2, the mice were consequently injected with individual nanoparticle complexes bearing either siRNA or doxorubicin at a dose of 1.2mg/Kg in both cases, once daily for three consecutive days . The results of this study demonstrated the effectiveness of such nanoparticle complexes for inhibiting tumour progression Inhibitors,research,lifescience,medical within the treated murine model groups, mainly due to impaired VEGF expression-related MDR . Other human cancer conditions which Inhibitors,research,lifescience,medical were investigated for circumvention of tumour MDR properties through
nanoparticle delivery include uterine sarcomas . In the study carried out by Huang et al. , pH-sensitive mesoporous silica nanoparticles incorporating hydrazine and doxorubicin were developed for in vivo testing on murine models of doxorubicin-resistant uterine sarcoma. Since the composition Inhibitors,research,lifescience,medical of such nanoparticles specifically allow for cellular uptake through endocytosis, bypassing of the P-gp efflux pump induced a marked reduction in P-gp dependent MDR properties . Consequently, the murine MDR tumour model treated with such nanoparticles demonstrated enhanced tumour apoptotic effects which were clearly confirmed by active caspase-3 immunohistochemical validation analysis . 6. Tubacin MM Conclusion The latest studies described above undoubtedly serve as a testament to the immense clinical value represented by nanoparticle technology. The ability of such nanoparticles, AV-951 irrelevant of biomaterial composition to efficiently load individual or combinations of chemotherapeutic drugs and/or chemosensitising agents (such as curcumin) and novel RNA interference-based therapies has been clearly demonstrated above. This property provides an excellent escape mechanism for circumventing target tumour cell multidrug resistance properties based on drug efflux pump activity on the tumour cell surface, such as that exerted by P-gp.