“…Organic dyes are widely applied for in vivo PA and fluorescence imaging due to the relatively low cytotoxicity and great clinical translation potential. − Nevertheless, as the absorption energy shifts to the NIR-II region, the photostability and absorption extinction coefficient would be a great challenge for organic dyes. ,− Furthermore, most of the recently developed NIR-II organic dyes exhibit poor solubility in aqueous solution, for instance, the NIR-II semiconducting polymers and cyanine derivative dyes (IR26, IR1061, and IR1048). ,,− Therefore, the dye@micelle system is one of the most applied strategy for in vivo administration of PA contrast agents to improve the biocompatibility and prolong the blood circulation time. , In general, to retain the photophysical properties of dyes (such as absorbance), the mass ratio between dye and amphiphilic molecules was applied as largely as possible (mass ratio about 1:1000) . Unfortunately, the amphiphilic molecules are known to be highly toxic and damage the cell membrane, the amount of which should be carefully controlled for in vivo application (the lower, the better) . Therefore, the administration dose of the dye@micelle system would be compromised between the in vivo cytotoxicity tolerance (dose of amphiphilic molecules) and in vivo PA signal (dose of dye).…”