Identification of a mitochondria-targeting fluorescent small molecule for dual phototherapy

Phototherapy,mainly induding photodynamic therapy(PDT)and photothermal therapy(PTT),is a noninvasive and effective approach for cancer treatment.Since integration of PDT and PTT for simultaneous synergistic PDT/PTT treatment enables us to improve phototherapeutic eficacy significantly,it has been attracting a lot of investigations in current days.Here,we introduce IR-52,a new mitochondria-targeting near infrared(NIR)fAuorescent small molecule,which possesses structure inherent PTT and PDT synergistic photother apeutic effects wit hout conjugation to specific ligands.After NIR light irradiation(808 nm,2 W/cm^(2),5min),both the hyperthermia and excessive singlet oaxygen levels were determined when dis-solving IR-52 in aqueous sohutions.In vitro photoinduced cytotoxicity studies showed signifcant lower cell viabilities and higher necrotic/apoptotic rates when cancer cells were treated with IR-52 and irradiation,and its'mitochondrial localization in cancer cells would partially explain its high cytotoxicity.Further in vivo synergetic PDT and PTT effects were demonstrated by high tumor surface temperature and sigmificant inhibition of tumor growth.Our results strongly suggest that IR-52,which possesses excellent photosensitivity,may provide a promising strategy for tumor treatment with decreased side effects.

PC4 serves as a negative regulator of skin wound healing in mice

Background:Human positive cofactor 4(PC4)was initially characterized as a multifunctional transcriptional cofactor,but its role in skin wound healing is still unclear.The purpose of this study was to explore the role of PC4 in skin wound healing through PC4 knock-in mouse model.Methods:A PC4 knock-in mouse model(PC4^(+/+))with a dorsal full-thickness wound was used to investigate the biological functions of PC4 in skin wound healing.Quantitative PCR,Western blot analysis and immunohistochemistry were performed to evaluate the expression of PC4;Sirius red staining and immunofluorescence were performed to explore the change of collagen deposition and angiogenesis.Proliferation and apoptosis were detected using Ki67 staining and TUNEL assay.Primary dermal fibroblasts were isolated from mouse skin to perform cell scratch experiments,cck-8 assay and colony formation assay.Results:The PC4^(+/+)mice were fertile and did not display overt abnormalities but showed an obvious delay in cutaneous healing of dorsal skin.Histological staining showed insufficient re-epithelialization,decreased angiogenesis and collagen deposition,increased apoptosis and decreased cell proliferation in PC4^(+/+)skin.Our data also showed decreased migration rate and proliferation ability in cultured primary fibroblasts from PC4^(+/+)mice in vitro.Conclusions:This study suggests that PC4 might serve as a negative regulator of skin wound healing in mice.