Jang, Yeon Lim Yun, Ui Jeong Lee, Min Sang Kim, Myung Goo Son, Sohee Lee, Kyuri Chae, Su Young Lim, Dong Woo Kim, Hong Tae Kim, Sun Hwa Jeong, Ji Hoon 2024-01-20T14:02:08Z 2024-01-20T14:02:08Z 2021-08-31 2012-09-15 0378-5173 https://pubs.kist.re.kr/handle/201004/128869 Cancer chemotherapy is often limited, since more than one molecule is usually involved with the cancer pathogenesis. A combination of therapeutic drugs would be a promising approach to overcome the complexity of tumors. In this study, a conjugate (DA3) of deoxycholic acid and low molecular weight polyethylenimine (PEI 1.8 kDa), which has a property that mimics that of cell penetrating peptides (CPPs), was used for simultaneous delivery of an anticancer drug and siRNA. When complexed with siRNA, DA3 showed significantly higher target gene silencing efficiency than PEI 25 kDa. The gene silencing efficiency of DA3 was maintained even in the presence of endocytosis inhibitors, suggesting that the polymeric carrier can mediate an endocytosis-independent macromolecular transduction similar to CPPs. The capability of forming a micelle-like core-shell structure enables the conjugates to encapsulate and dissolve paclitaxel (PTX), a water-insoluble drug. The drug-loaded cationic micelles can then interact with siRNA to form stable complexes (PTX/DA3/siRNA). The PTX/DA3/siRNA showed significantly enhanced inhibition of cancer cell growth. When administered into tumor-bearing animals, the PTX/DA3/siRNA demonstrated significant suppression of tumor growth, providing potential usefulness in clinical settings. (C) 2012 Elsevier B.V. All rights reserved. English ELSEVIER SCIENCE BV RNA INTERFERENCE GENE-THERAPY CANCER-CELLS HUMAN BREAST CO-DELIVERY VEGF SIRNA EXPRESSION XIAP ADENOCARCINOMA CHEMOTHERAPY Cell-penetrating peptide mimicking polymer-based combined delivery of paclitaxel and siRNA for enhanced tumor growth suppression Article 10.1016/j.ijpharm.2012.04.083 1 INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.434, no.1-2, pp.488 - 493 INTERNATIONAL JOURNAL OF PHARMACEUTICS 434 1-2 488 493 scie scopus 000306479400058 2-s2.0-84864140974 Pharmacology & Pharmacy Pharmacology & Pharmacy Article RNA INTERFERENCE GENE-THERAPY CANCER-CELLS HUMAN BREAST CO-DELIVERY VEGF SIRNA EXPRESSION XIAP ADENOCARCINOMA CHEMOTHERAPY Biomimetic polymer Combined delivery siRNA Anticancer drug Combination cancer therapy