Aptamer-functionalized pH-sensitive liposomes for a selective delivery of echinomycin into cancer cells

被引:28
|
作者
Lafi, Zainab [1 ,2 ]
Alshaer, Walhan [3 ]
Hatmal, Ma'mon M. [4 ]
Zihlif, Malek [5 ]
Alqudah, Dana A. [3 ]
Nsairat, Hamdi [6 ]
Azzam, Hanan [7 ]
Aburjai, Talal [8 ]
Bustanji, Yasser [9 ]
Awidi, Abdalla [3 ,10 ,11 ]
机构
[1] Middle East Univ, Fac Pharm, Amman, Jordan
[2] Univ Jordan, Fac Pharm, Dept Clin Pharm, Amman 11942, Jordan
[3] Univ Jordan, Cell Therapy Ctr, Amman 11942, Jordan
[4] Hashemite Univ, Fac Appl Med Sci, Dept Med Lab Sci, Zarqa 13133, Jordan
[5] Univ Jordan, Fac Med, Dept Pharmacol, Amman 11942, Jordan
[6] Al Ahliyya Amman Univ, Fac Pharm, Pharmacol & Diagnost Res Ctr, Amman 19328, Jordan
[7] Univ Jordan, HMCSR, Amman 11942, Jordan
[8] Univ Jordan, Fac Pharm, Dept Pharmaceut Sci, Amman 11942, Jordan
[9] Univ Sharjah, Coll Med, Dept Basic Med Sci, Sharjah 27272, U Arab Emirates
[10] Univ Jordan, Fac Med, Dept Internal Med, Amman 11942, Jordan
[11] Univ Jordan, Jordan Univ Hosp, Dept Hematol & Oncol, Amman 11942, Jordan
关键词
IN-VITRO; DRUG-DELIVERY; CHOLESTEROL; FORMULATION; BEHAVIOR; BINDING; SYSTEMS; MURINE;
D O I
10.1039/d1ra05138e
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Echinomycin (quinomycin A) is a peptide antibiotic from the quinoxaline family, which has a DNA bifunctional intercalating activity and an inhibitor of hypoxia-inducible factor (HIF1 alpha). Echinomycin was discovered in 1957 as a potent antitumor agent; however, it was not successful in clinical use due to its low water solubility and short half-life. To revitalize this potent drug, it is important to increase its aqueous solubility and bioavailability. In this study, echinomycin was loaded into PEGylated pH-sensitive liposomes ((PEG)Lip(pH)) and functionalized with anti-nucleolin aptamer (Apt(NCL)) for selective targeting and pH-responsive release of echinomycin into cancer cells. Echinomycin was complexed with gamma-cyclodextrin (EC gamma CD) to enhance its water solubility and then encapsulated into pH-sensitive liposomes ((PEG)Lip(pH)-EC gamma CD). Then, liposomes were functionalized with Apt(NCL) (Apt(NCL-PEG)Lip(pH)-EC gamma CD) and the successful functionalization was confirmed by dynamic light scattering (DLS) measurements and gel electrophoresis. Cellular uptake for Apt(NCL-PEG)Lip(pH) was evaluated by flow cytometry analysis using MDA-MB-231, MCF7, A549 cancer cell lines with respect to the normal fibroblast cells. The results showed a higher uptake and selectivity for Apt(NCL-PEG)Lip(pH) compared to (PEG)Lip(pH). The anti-proliferative effects of Apt(NCL-PEG)Lip(pH)-EC gamma CD were more potent than (PEG)Lip(pH)-EC gamma CD by 3.5, 4, and 5 folds for A549, MDA-MB-231, and MCF7, respectively. Selectivity indices (SI) for Apt(NCL-PEG)Lip(pH)-EC gamma CD for the tumor cell lines compared to the normal cell line after 72 h were MDA-MB-231 (43.3), MCF7 (16.9), and A549 (8.5). Furthermore, SI after 3 h for the three cancer cell lines were 4.7, 2.5, 2.8, respectively.
引用
收藏
页码:29164 / 29177
页数:14
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