New combination treatment from ROS-Induced sensitized radiotherapy with nanophototherapeutics to fully eradicate orthotopic breast cancer and inhibit metastasis
Journal
Biomaterials
Journal Volume
257
Pages
120229
Date Issued
2020
Author(s)
Liu, T.-I. ; Lu, T.-Y. ; Chang, S.-H. ; Chen, H.-H.a, ; Lu, I.-L. ; Sabu, A. ; Chiu, H.-C.
Abstract
Radiotherapy (RT) is one of the most commonly employed approaches in the treatment of malignant tumors and is often combined with radiosensitizers to enhance the therapeutic efficacy for clinical use. For developing a smart therapeutic strategy leveraging local tissue response to photo-mediated reactions and the combination of multiple treatment modalities involving ROS-induced sensitization of RT, a novel nanophototherapeutic system has been developed. The nanotherapeutics prepared from the assembly of poly (thiodiethylene malonate) (PSDEM) and PEG-PSDEM-PEG and loaded with suberoylanilide hydroxamic acid (SAHA) employed as the RT sensitizer and indocyanine green (ICG) as the photothermal/photodynamic agent, demonstrated the capability of undergoing structural change and releasing therapeutic payloads in response to near-infrared irradiation and X-ray radiotherapy. With highly localized and controllable reactions within the tumor site, the reactive oxygen species (ROS)-triggered SAHA unloading and the hyperthermia-induced vascular permeability of oxygen led to a significant sensitization of the target tissue in RT, which, in turn, led to the promotion of therapeutic effect in conjunction with photodynamic/photothermal therapies (PDT/PTT). In vitro studies demonstrated the damage in intracellular DNA double strands and the inhibition of cell proliferation in 4T1 breast cancer cells treated with ROS-induced sensitized RT. A substantial reduction in cell viability was also observed owing to the effects of the combination of photo-mediated treatments with sensitized RT compared to the effects of RT administration alone. Complete eradication of the primary tumor and the inhibition of lung metastasis was observed in five of six orthotopic 4T1 breast cancer-bearing mice subjected to combined PDT/PTT in nanophototherapeutics with ROS-induced sensitized RT at a low dosage (6 Gy), leading to the prominent survival fraction of ca. 83% over 60 days. ? 2020 Elsevier Ltd
Subjects
Combination therapy; Photothermal/photodynamic therapies; Radiosensitizer; Radiotherapy; Stimulus-induced drug release
SDGs
Other Subjects
Cell proliferation; Infrared devices; Mammals; Oxygen; Pathology; Radiotherapy; Tumors; Unloading; Breast cancer cells; Combination treatments; Suberoylanilide hydroxamic acids; Substantial reduction; Therapeutic effects; Therapeutic efficacy; Therapeutic strategy; Vascular permeability; Diseases; cell DNA; ethylene derivative; indocyanine green; macrogol; malonic acid derivative; nanocarrier; oxygen; poly(thiodiethylene malonate); reactive oxygen metabolite; unclassified drug; vorinostat; indocyanine green; reactive oxygen metabolite; 4T1 cell line; animal cell; animal experiment; animal model; animal tissue; Article; blood vessel permeability; breast cancer; cancer control; cancer inhibition; cancer radiotherapy; cancer survival; cancer tissue; cancer transplantation; cell proliferation; cell viability; controlled study; double stranded DNA break; drug delivery system; drug release; female; in vitro study; irradiation; low energy radiation; lung metastasis; metastasis inhibition; mouse; nanoencapsulation; nanopharmaceutics; nonhuman; orthotopic transplantation; photodynamic therapy; photothermal therapy; primary tumor; priority journal; radiosensitization; survival rate; thermotherapy; animal; breast tumor; human; photochemotherapy; phototherapy; thermotherapy; tumor cell line; Animals; Breast Neoplasms; Cell Line, Tumor; Humans; Hyperthermia, Induced; Indocyanine Green; Mice; Photochemotherapy; Phototherapy; Reactive Oxygen Species
Type
journal article