A nano-complex system to overcome antagonistic photo-chemo combination cancer therapy
- Authors
- Lim, Chaemin; Moon, Junseong; Sim, Taehoon; Won, Woong Roeck; Lee, Eun Seong; Youn, Yu Seok; Oh, Kyung Taek
- Issue Date
- Feb-2019
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Photo-chemo combination therapy; Chlorin e6; Doxorubicin; pH sensitive; MDR; Synergism
- Citation
- JOURNAL OF CONTROLLED RELEASE, v.295, pp 164 - 173
- Pages
- 10
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- Volume
- 295
- Start Page
- 164
- End Page
- 173
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/18269
- DOI
- 10.1016/j.jconrel.2018.12.043
- ISSN
- 0168-3659
1873-4995
- Abstract
- Photo-Chemo combination therapy has been intensively investigated for treatment of cancers, especially multidrug resistance cancer. However, antagonistic interactions between chemo-drugs and photosensitizers are frequently reported, and drugs doses and treatment sequences have been changed to overcome the problems. We observed the antagonistic effect by a decrease in singlet oxygen generation from the photosensitizer when Dox was in close physical proximity. To control the distance between Dox and the photosensitizer, we developed a novel pH-sensitive poly ionomer complex system composed of PEG-PLL(-g-Ce6) [Chlorin e6 grafted poly(ethylene glycol)-poly(L-lysine)] and PEG-PLL(-g-DMA)-PLA [2,3-dimethylmaleic anhydride grafted poly(ethylene glycol)-poly(L-lysine)-poly(lactic acid)] and evaluated this system with regard to singlet oxygen generation and antiproliferative activity against MCF-7/Dox cells. Enhanced singlet oxygen generation and antiproliferative activities were observed in vitro and in vivo for the poly ionomer complex system compared to PEG-PLL(-g-Ce6)-PLA/Dox due to the change in distance between Dox and Ce6 in the PIC system under acidic conditions. Our results highlight the importance of interactions between co-loaded drugs in combination therapy, and provide new insights into design principles for tailor-made nanomedicine platforms.
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