Yinan Ding1, Rui Yang2, Weiping Yu1, Chunmei Hu3, Zhiyuan Zhang4, Dongfang Liu1, Yanli An5, Xihui Wang1, Chen He1, Peidang Liu1, Qiusha Tang6, Daozhen Chen7. 1. Medical School of Southeast University, Nanjing, 210009, China. 2. Research Institute for Reproductive Health and Genetic Diseases, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, 214002, China. 3. Department of Tuberculosis, The Second Affiliated Hospital of Southeast University (The Second Hospital of Nanjing), Nanjing, 210009, China. 4. Department of Neurosurgery, Nanjing Jinling Hospital, Nanjing University, Nanjing, 210002, China. 5. Affiliated Zhongda Hospital of Southeast University, Nanjing, 210009, China. 6. Medical School of Southeast University, Nanjing, 210009, China. panyixi-tqs@163.com. 7. Research Institute for Reproductive Health and Genetic Diseases, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, 214002, China. chendaozhen@163.com.
Abstract
BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive tumor with extremely high mortality that results from its lack of effective therapeutic targets. As an adhesion molecule related to tumorigenesis and tumor metastasis, cluster of differentiation-44 (also known as CD44) is overexpressed in TNBC. Moreover, CD44 can be effectively targeted by a specific hyaluronic acid analog, namely, chitosan oligosaccharide (CO). In this study, a CO-coated liposome was designed, with Photochlor (HPPH) as the 660 nm light mediated photosensitizer and evofosfamide (also known as TH302) as the hypoxia-activated prodrug. The obtained liposomes can help diagnose TNBC by fluorescence imaging and produce antitumor therapy by synergetic photodynamic therapy (PDT) and chemotherapy. RESULTS: Compared with the nontargeted liposomes, the targeted liposomes exhibited good biocompatibility and targeting capability in vitro; in vivo, the targeted liposomes exhibited much better fluorescence imaging capability. Additionally, liposomes loaded with HPPH and TH302 showed significantly better antitumor effects than the other monotherapy groups both in vitro and in vivo. CONCLUSION: The impressive synergistic antitumor effects, together with the superior fluorescence imaging capability, good biocompatibility and minor side effects confers the liposomes with potential for future translational research in the diagnosis and CD44-overexpressing cancer therapy, especially TNBC.
BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive tumor with extremely high mortality that results from its lack of effective therapeutic targets. As an adhesion molecule related to tumorigenesis and tumor metastasis, cluster of differentiation-44 (also known as CD44) is overexpressed in TNBC. Moreover, CD44 can be effectively targeted by a specific hyaluronic acid analog, namely, chitosan oligosaccharide (CO). In this study, a CO-coated liposome was designed, with Photochlor (HPPH) as the 660 nm light mediated photosensitizer and evofosfamide (also known as TH302) as the hypoxia-activated prodrug. The obtained liposomes can help diagnose TNBC by fluorescence imaging and produce antitumor therapy by synergetic photodynamic therapy (PDT) and chemotherapy. RESULTS: Compared with the nontargeted liposomes, the targeted liposomes exhibited good biocompatibility and targeting capability in vitro; in vivo, the targeted liposomes exhibited much better fluorescence imaging capability. Additionally, liposomes loaded with HPPH and TH302 showed significantly better antitumor effects than the other monotherapy groups both in vitro and in vivo. CONCLUSION: The impressive synergistic antitumor effects, together with the superior fluorescence imaging capability, good biocompatibility and minor side effects confers the liposomes with potential for future translational research in the diagnosis and CD44-overexpressing cancer therapy, especially TNBC.
Entities:
Keywords:
CD44; Chitosan oligosaccharide; Liposomes; Photodynamic therapy; Triple negative breast cancer
Authors: Andrew Tutt; Holly Tovey; Maggie Chon U Cheang; Sarah Kernaghan; Lucy Kilburn; Patrycja Gazinska; Julie Owen; Jacinta Abraham; Sophie Barrett; Peter Barrett-Lee; Robert Brown; Stephen Chan; Mitchell Dowsett; James M Flanagan; Lisa Fox; Anita Grigoriadis; Alexander Gutin; Catherine Harper-Wynne; Matthew Q Hatton; Katherine A Hoadley; Jyoti Parikh; Peter Parker; Charles M Perou; Rebecca Roylance; Vandna Shah; Adam Shaw; Ian E Smith; Kirsten M Timms; Andrew M Wardley; Gregory Wilson; Cheryl Gillett; Jerry S Lanchbury; Alan Ashworth; Nazneen Rahman; Mark Harries; Paul Ellis; Sarah E Pinder; Judith M Bliss Journal: Nat Med Date: 2018-04-30 Impact factor: 53.440