Um, Wooram Park, Jooho Ko, Hokyung Lim, Seungho Yoon, Hong Yeol Shim, Man Kyu Lee, Sangmin Ko, Young Ji Kim, Min Ju Park, Jae Hyung Lim, Dong-Kwon Byun, Youngro Kwon, Ick Chan Kim, Kwangmeyung 2024-01-19T18:33:46Z 2024-01-19T18:33:46Z 2021-09-05 2019-12 0142-9612 https://pubs.kist.re.kr/handle/201004/119271 The therapeutic efficacy of photodynamic therapy (PDT) in cancer treatment is attributed to the conversion of tumor oxygen into reactive singlet oxygen (O-1(2)) using photosensitizers. However, poor tissue penetration and rapid oxygen depletion have limited the effectiveness of PDT. Therefore, we have developed visible light-induced apoptosis activatable nanoparticles of the photosensitizer (Ce6)-caspase 3 cleavable peptide (Asp-Glu-Val-Asp, DEVD)-anticancer drug monomethyl auristatin E (MMAE) conjugate, resulting in Ce6-DEVD-MMAE nanoparticles. The average size of self-assembled Ce6-DEVD-MMAE nanoparticles was 90.8 +/- 18.9 nm. Compared with conventional PDT based on high-energy irradiation, the new therapy uses lower-energy irradiation to induce apoptosis of cancer cells, and activation of caspase 3 to successfully cleave the anticancer drug MMAE from the Ce6-DEVD-MMAE nanoparticles, resulting in strong cytotoxic effects in cancer cells. Notably, the one-time activation of MMAE in the Ce6-DEVD-MMAE nanoparticles further amplified the cytotoxic effect resulting in additional cell death in the absence of visible light irradiation. Furthermore, Ce6-DEVD-MMAE nanoparticles passively accumulated in the targeted tumor tissues via enhanced permeation and retention (EPR) effect in mice with squamous cell carcinoma (SCC7). The high levels of toxicity were retained after exposure to lower-energy irradiation. However, Ce6-DEVD-MMAE nanoparticles did not show any toxicity in the absence of exposure to visible light irradiation, in contrast to the toxicity of free MMAE (1-10 nM). Thus, the light-induced therapeutic strategy based on apoptotic activation of Ce6-DEVD-MMAE nanoparticles can be used to treat solid tumors inaccessible to conventional PDT. English ELSEVIER SCI LTD Visible light-induced apoptosis activatable nanoparticles of photosensitizer-DEVD-anticancer drug conjugate for targeted cancer therapy Article 10.1016/j.biomaterials.2019.119494 1 BIOMATERIALS, v.224 BIOMATERIALS 224 N scie scopus 000490628500013 2-s2.0-85072302609 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article PHOTODYNAMIC THERAPY DELIVERY PRODRUG GENERATION PRINCIPLES IMPROVES Nanomedicine Photodynamic therapy Self-assembly Apoptosis Targeted cancer therapy Cytotoxic prodrug