Water-solubility croconic acid-bisindole dye with morpholine ring for tumor NIRF/PA imaging and photothermal therapy activated by lysosome pH-response.

A novel croconic acid-bisindole dye CR-630 with a morpholine ring showed good water-solubility and obvious lysosome-targeting. The protonation of the nitrogen atom in the indole and lysosome-targeting of morpholine ring let it exhibit stronger pH-responsive NIR/PA imaging and photothermal effect in the lysosome acidic microenvironment (pH 4.0-5.5) than in the tumor acidic microenvironment. In the animal study, compound CR-630 could NIRF/PA image in the tumor tissues in 1.5-2.0 h, effectively inhibit the growth of the tumor, and even ablate the tumor at the drug dose of 1 mg/kg. It also demonstrated good biosafety. This study gives a new idea to develop water-solubility organic dyes with lysosome targeting, stronger pH-responsive NIRF/PA imaging and PTT for breast cancer.

NIR C-Myc Pu22 G-quadruplex probe as a photosensitizer for bioimaging and antitumor study.

Despite the fact that C-Myc G-quadruplex in the oncogene promoter regions is one of the crucial targets of antitumor drugs, the selectivities and proliferation inhibitions of its probes towards tumor cells remain a big challenge. Until now, no effective C-Myc G-quadruplex probes have been reported as a photosensitizer to increase their antitumor activities. Here, the first NIR C-Myc G-quadruplex probe PDS-SQ has been designed, comprising a G-quadruplex binder PDS and a squaraine dye SQ as a photosensitizer. Conjugate PDS-SQ could selectively NIR image C-Myc Pu22 G-quadruplex in tumor cells, and show stronger antitumor activity in the irradiation by a chemo-photodynamic method than in the dark. The study provides a new way to develop the novel NIR C-Myc G-quadruplex probes with more potent antitumor activities.

Single aromatics sulfonamide substituted dibenzothiazole squaraines for tumor NIR imaging and efficient photodynamic therapy at low drug dose.

On the base of the zwiterionic dibenzothiazole squaraine SQ, five cationic aromatics sulfonamide substituted dibenzothiazole squaraines SQ-D1 âˆ¼ 5 have been designed and synthesized. Through the formation of the cationic compound, a higher rigid structure and the addition of the strong electron-withdrawing group (-CN), an ideal photosensitizer SQ-D2 has been gotten. In all the sulfonaminosquaraines, compound SQ-D2 exhibited the highest ROS generation efficacy and photostability. It also showed the highest photo-cytotoxicity (IC50 = 0.25 ± 0.08 µM), very low dark-cytotoxicity and the excellent cell uptake. In animal study, it not only showed the effective tumor retention and the easy removal from the body, but also exhibited the effective PDT efficacy at low drug dose (0.15 mg/kg) and the good biocompatibility. Furthermore, photosensitizer SQ-D2 as a single component exhibited greater potential than clinically approved photosensitizer m-THPC and some nanomaterials with photosensitizers in PDT therapy towards human breast cancer. This work provides a new perspective to develop the ideal photosensitizer of the squaraine dyes.

G-quadruplex binder pyridostatin as an effective multi-target ZIKV inhibitor.

At present, there are still no anti-Zika virus (ZIKV) drugs or vaccines approved by FDA with accurate targets and antiviral mechanisms. Considering the RNA G-quadruplex sequences in ZIKV genome, it is very meaningful to develop G-quadruplex binders as potential anti-ZIKV drugs with novel and accurate targets. In this paper, five classical G-quadruplex binders including Ber, Braco 19, NiL, 360A and PDS have been chosen to discuss their interaction with ZIKV RNA G-quadruplexes. PDS shows higher binding affinity and thermal stability than the other G-quadruplex binders. This property is further evidenced in cells by immunofluorescence microscopy. And PDS shows higher anti-ZIKV activity (EC50 = 4.2 ± 0.4 µM) than the other G-quadruplex binders as well as the positive control ribavirin, with a low cytotoxicity. By time-of-addition assay, PDS exerts antiviral activity at the post-entry process of ZIKV replication cycle, thus inhibiting ZIKV mRNA replication and protein expression. Furthermore, PDS combines with ZIKV NS2B-NS3 protease and reduces its catalytic activity. This study suggests that G-quadruplex binder PDS is an effective multi-target ZIKV inhibitor, which provides more guidance to design some novel anti-ZIKV drugs targeting ZIKV RNA G-quadruplexes.