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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 Elsevier 2019 Biomaterials Vol.224 No.-
<P><B>Abstract</B></P> <P>The therapeutic efficacy of photodynamic therapy (PDT) in cancer treatment is attributed to the conversion of tumor oxygen into reactive singlet oxygen (<SUP>1</SUP>O<SUB>2</SUB>) 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 (<I>Asp-Glu-Val-Asp</I>, 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 <I>via</I> 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.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>