AIM To improve the treatment efficacy of anti tumor drug mitoxantrone, the conjugation of mitoxantrone loaded nanospheres and anti C erbB 2 monoclonal antibodies were prepared. METHODS Mitoxantrone loaded nanospheres ...AIM To improve the treatment efficacy of anti tumor drug mitoxantrone, the conjugation of mitoxantrone loaded nanospheres and anti C erbB 2 monoclonal antibodies were prepared. METHODS Mitoxantrone loaded nanospheres were prepared with emulsion heating solidification technique. A heterobifunctional reagent, N succinimidyl 3 (2 pyridyldithio) propionate (SPDP), was used as the crosslinker of mitoxantrone loaded nanospheres and anti C erbB 2 monoclonal antibodies; pharmaceutical properties of immunonanocapsuls were studied; the conjugates of nanospheres and monoclonal antibodies was confirmed with immunological methods such as slide agglutination test, fluorescent immunossay and rosset formation test, fluorescent staining and scanning electron microscope. RESULTS Mitoxantrone loaded nanospheres were spherical, with smooth surface and median diameter of 0 665 micron. When stored at 3-5, 20-25 and 37℃, RH 75% for three months, the appearance, morphology, size distribution, drug loading and in vitro release characteristics showed no significant change and the stability was satisfactory. The size analysis demonstrated that there was no obvious increase in the particle size of nanoparticles after conjugation. Immunological tests indicate highly selective binding of antibody targeted nanospheres to C erbB 2 overexpressing cells SK BR 3. CONCLUSION The conjugation of mitoxantrone loaded nanospheres and anti C erbB 2 monoclonal antibodies can keep the activity of anti C erbB 2 and increase the therapeutic efficacy of anti mammary cancer drugs.展开更多
文摘AIM To improve the treatment efficacy of anti tumor drug mitoxantrone, the conjugation of mitoxantrone loaded nanospheres and anti C erbB 2 monoclonal antibodies were prepared. METHODS Mitoxantrone loaded nanospheres were prepared with emulsion heating solidification technique. A heterobifunctional reagent, N succinimidyl 3 (2 pyridyldithio) propionate (SPDP), was used as the crosslinker of mitoxantrone loaded nanospheres and anti C erbB 2 monoclonal antibodies; pharmaceutical properties of immunonanocapsuls were studied; the conjugates of nanospheres and monoclonal antibodies was confirmed with immunological methods such as slide agglutination test, fluorescent immunossay and rosset formation test, fluorescent staining and scanning electron microscope. RESULTS Mitoxantrone loaded nanospheres were spherical, with smooth surface and median diameter of 0 665 micron. When stored at 3-5, 20-25 and 37℃, RH 75% for three months, the appearance, morphology, size distribution, drug loading and in vitro release characteristics showed no significant change and the stability was satisfactory. The size analysis demonstrated that there was no obvious increase in the particle size of nanoparticles after conjugation. Immunological tests indicate highly selective binding of antibody targeted nanospheres to C erbB 2 overexpressing cells SK BR 3. CONCLUSION The conjugation of mitoxantrone loaded nanospheres and anti C erbB 2 monoclonal antibodies can keep the activity of anti C erbB 2 and increase the therapeutic efficacy of anti mammary cancer drugs.
文摘双硫仑作为一种治疗慢性酒精中毒的药物在临床中广泛使用。近年来,研究者提出了双硫仑治疗癌症的具体机制,如抑制乙醛脱氢酶(acetaldehyde dehydrogenase,ALDH)的活性、提高细胞内活性氧(reactive oxygen species,ROS)的浓度、抑制核因子kappa-B(nuclear factor kappa-B,NF-κB)的活性,促进与核蛋白定位蛋白4(nuclear protein localization protein 4,NPL4)的结合、抑制FROUNT蛋白等,并在多种癌症模型中证明了双硫仑的抗癌活性。抗肾小球基底膜型肾小球肾炎是急进性肾小球肾炎中的一种类型,该病一旦被确诊,就需要第一时间给予治疗,尽量帮助患者缓解症状、改善预后。研究表明,双硫仑可通过抑制C-C趋化因子受体2型/C-C趋化因子受体5型(C-C chemokine receptor type 2/C-C chemokine receptor type 5,CCR-2/CCR-5)和FROUNT蛋白之间的相互作用来抑制巨噬细胞的迁移、聚集、活化来缓解抗肾小球基底膜型肾小球肾炎,这表明双硫仑对该类患者具有潜在的治疗价值。本文简要回顾了双硫仑最新研究中阐明的相关作用分子机制,展望了未来双硫仑作为新的药物治疗抗肾小球基底膜型肾小球肾炎的前景。
