Le Quang Thao1, Hyeong Jun Byeon1, Changkyu Lee1, Seunghyun Lee1, Eun Seong Lee2, Yeon Woong Choi3, Han-Gon Choi4, Eun-Seok Park1, Kang Choon Lee1, Yu Seok Youn5. 1. School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, 16419, Republic of Korea. 2. Division of Biotechnology, The Catholic University of Korea, 43-1 Yeokgok 2-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea. 3. Korea United Pharm. INC., 514-8 Nonhyung-dong, Kangnam-gu, Seoul, 06114, Republic of Korea. 4. College of Pharmacy, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan, 15588, Republic of Korea. 5. School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, 16419, Republic of Korea. ysyoun@skku.edu.
Abstract
PURPOSE: We developed a new nanoparticle formulation comprised of human serum albumin (HSA) for co-delivery of doxorubicin (Dox) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with the goal of apoptotic synergy in the treatment of colon cancer. METHODS: TRAIL (0.2, 0.4, 1.0%)- and Dox-loaded HSA nanoparticles (TRAIL/Dox HSA NPs) were prepared by using the nab(TM) technology. Morphological and physicochemical characterizations were investigated by dynamic light scattering and transmission electron microscopy. Synergistic cytotoxicity, apoptotic activity, and potential penetration into mass tumor were determined in HCT116 cell-based systems. Furthermore, antitumor efficacy and tumor targeting were also investigated. RESULTS: TRAIL/Dox HSA NPs were uniformly spherical with sizes of 60 ~ 120 nm. The encapsulation efficacy of Dox and TRAIL was 68.9-77.2% and 80.4-86.0%, respectively. TRAIL 1.0%/Dox HSA NPs displayed the best inhibition of HCT116 colon cancer cells; inhibition was 6 times higher than achieved with Dox HSA NPs. The TRAIL 1.0%/Dox HSA NPs formulation was studied further. Flow cytometry analysis and TUNEL assay revealed that TRAIL 1.0%/Dox HSA NPs had markedly greater apoptotic activity than Dox HSA NPs. In HCT116 tumor-bearing BALB/c nu/nu mice, TRAIL 1.0%/Dox HSA NPs had significantly higher antitumor efficacy than Dox HSA NPs (tumor volume; 933.4 mm(3) vs. 3183.7 mm(3), respectively). TRAIL 1.0%/Dox HSA NPs penetrated deeply into tumor masses in a HCT116 spheroid model and localized in tumor sites after tail vein injection. CONCLUSIONS: Data indicate that TRAIL 1.0%/Dox HSA NPs offer advantages of co-delivery of Dox and TRAIL in tumors, with potential synergistic apoptosis-based anticancer therapy.
PURPOSE: We developed a new nanoparticle formulation comprised of humanserum albumin (HSA) for co-delivery of doxorubicin (Dox) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with the goal of apoptotic synergy in the treatment of colon cancer. METHODS:TRAIL (0.2, 0.4, 1.0%)- and Dox-loaded HSA nanoparticles (TRAIL/DoxHSA NPs) were prepared by using the nab(TM) technology. Morphological and physicochemical characterizations were investigated by dynamic light scattering and transmission electron microscopy. Synergistic cytotoxicity, apoptotic activity, and potential penetration into mass tumor were determined in HCT116 cell-based systems. Furthermore, antitumor efficacy and tumor targeting were also investigated. RESULTS:TRAIL/DoxHSA NPs were uniformly spherical with sizes of 60 ~ 120 nm. The encapsulation efficacy of Dox and TRAIL was 68.9-77.2% and 80.4-86.0%, respectively. TRAIL 1.0%/DoxHSA NPs displayed the best inhibition of HCT116 colon cancer cells; inhibition was 6 times higher than achieved with DoxHSA NPs. The TRAIL 1.0%/DoxHSA NPs formulation was studied further. Flow cytometry analysis and TUNEL assay revealed that TRAIL 1.0%/DoxHSA NPs had markedly greater apoptotic activity than DoxHSA NPs. In HCT116 tumor-bearing BALB/c nu/nu mice, TRAIL 1.0%/DoxHSA NPs had significantly higher antitumor efficacy than DoxHSA NPs (tumor volume; 933.4 mm(3) vs. 3183.7 mm(3), respectively). TRAIL 1.0%/DoxHSA NPs penetrated deeply into tumor masses in a HCT116 spheroid model and localized in tumor sites after tail vein injection. CONCLUSIONS: Data indicate that TRAIL 1.0%/DoxHSA NPs offer advantages of co-delivery of Dox and TRAIL in tumors, with potential synergistic apoptosis-based anticancer therapy.
Authors: W Russ Algar; Duane E Prasuhn; Michael H Stewart; Travis L Jennings; Juan B Blanco-Canosa; Philip E Dawson; Igor L Medintz Journal: Bioconjug Chem Date: 2011-05-18 Impact factor: 4.774
Authors: Lindsay K Hill; Joseph A Frezzo; Priya Katyal; Dung Minh Hoang; Zakia Ben Youss Gironda; Cynthia Xu; Xuan Xie; Erika Delgado-Fukushima; Youssef Z Wadghiri; Jin Kim Montclare Journal: ACS Nano Date: 2019-02-19 Impact factor: 15.881
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