Nanoparticle formulation of ormeloxifene for pancreatic cancer.
Nanoparticle formulation of ormeloxifene for pancreatic cancer.
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DOI：
10.1016/j.biomaterials.2015.02.082
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发表时间：
2015
期刊：
影响因子：
14
通讯作者：
Chauhan, Subhash C.
中科院分区：
文献类型：
--
作者：
Khan, Sheema;Chauhan, Neeraj;Yallapu, Murali M.;Ebeling, Mara C.;Balakrishna, Swathi;Ellis, Robert T.;Thompson, Paul A.;Balabathula, Pavan;Behrman, Stephen W.;Zafar, Nadeem;Singh, Man M.;Halaweish, Fathi T.;Jaggi, Meena;Chauhan, Subhash C.
胰腺癌是第四大最常见的癌症，死亡率约为85%；因此，迫切需要找到新的治疗方法，以最小或没有副作用地提高这种疾病的治疗结果。奥美洛昔芬(ORM)是一种人工合成的分子，通过抑制重要的致癌和增殖信号通路而显示出强大的抗癌作用。然而，ORM的抗癌效果可以通过开发其纳米制剂进一步提高，该纳米制剂也将提供肿瘤特异性靶向递送。因此，我们开发了一种新型的ORM包裹的聚(乳酸-乙醇酸)纳米粒(NP)制剂(PLGA-ORM NP)。采用不同的物理化学方法(透射电子显微镜、红外光谱、差示扫描量热法、热重分析法和高效液相色谱法)对该制剂的颗粒大小、化学成分和载药效率进行了表征。由于其组成简单，这种新的剂型可以与抗体/适配子结合相容，以实现肿瘤特异性靶向。该PLGA-ORM制剂的粒径分析(~100 nm)表明，该制剂可通过增强渗透性和滞留(EPR)效应优先到达并在肿瘤体内蓄积。细胞摄取和内化研究表明，PLGA-ORM纳米粒可逃脱溶酶体的降解，为胞浆提供有效的内体释放。PLGA-ORM纳米粒在多种胰腺癌细胞(HPAF-II、BxPC-3、PANC-1、MiaPaca)和BxPC-3异种移植小鼠模型中显示出显著的抗癌活性，从而提高了动物的存活率。PLGA-ORM纳米粒通过抑制Akt的磷酸化和MUC1、HER2、增殖细胞核抗原、CK19和CD31的表达而抑制胰腺肿瘤的生长。本研究表明，PLGA-ORM制剂对胰腺肿瘤的生长有较高的抑制作用，对胰腺癌的治疗有一定的应用价值。
Pancreatic cancer is the fourth most prevalent cancer with about an 85% mortality rate; thus, an utmost need exists to discover new therapeutic modalities that would enhance therapy outcomes of this disease with minimal or no side effects. Ormeloxifene (ORM), a synthetic molecule, has exhibited potent anti-cancer effects through inhibition of important oncogenic and proliferation signaling pathways. However, the anti-cancer efficacy of ORM can be further improved by developing its nanoformulation, which will also offer tumor specific targeted delivery. Therefore, we have developed a novel ORM encapsulated poly(lactic-co-glycolic acid) nanoparticle (NP) formulation (PLGA-ORM NP). This formulation was characterized for particle size, chemical composition, and drug loading efficiency, using various physico-chemical methods (TEM, FT-IR, DSC, TGA, and HPLC). Because of its facile composition, this novel formulation is compatible with antibody/aptamer conjugation to achieve tumor specific targeting. The particle size analysis of this PLGA-ORM formulation (~ 100 nm) indicates that this formulation can preferentially reach and accumulate in tumors by the Enhanced Permeability and Retention (EPR) effect. Cellular uptake and internalization studies demonstrate that PLGA-ORM NPs escape lysosomal degradation, providing efficient endosomal release to cytosol. PLGA-ORM NPs showed remarkable anti-cancer potential in various pancreatic cancer cells (HPAF-II, BxPC-3, Panc-1, MiaPaca) and a BxPC-3 xenograft mice model resulting in increased animal survival. PLGA-ORM NPs suppressed pancreatic tumor growth via suppression of Akt phosphorylation and expression of MUC1, HER2, PCNA, CK19 and CD31. This study suggests that the PLGA-ORM formulation is highly efficient for the inhibition of pancreatic tumor growth and thus can be valuable for the treatment of pancreatic cancer in the future.
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影响因子：
5.7
作者：
Chauhan SC;Ebeling MC;Maher DM;Koch MD;Watanabe A;Aburatani H;Lio Y;Jaggi M
通讯作者：
Jaggi M
多乳酸 - 糖苷糖纳米颗粒，用于控制抗癌剂的递送。
影响因子：
8
作者：
Dinarvand R;Sepehri N;Manoochehri S;Rouhani H;Atyabi F
通讯作者：
Atyabi F
影响因子：
29.4
作者：
Farrell, James J.;Elsaleh, Hany;Mackey, John R.
通讯作者：
Mackey, John R.
影响因子：
2.9
作者：
Bansode, FW;Chauhan, SC;Singh, MM
通讯作者：
Singh, MM
影响因子：
11.2
作者：
Chauhan, Subhash C.;Vannatta, Kelley;Jaggi, Meena
通讯作者：
Jaggi, Meena