It is challenging to develop molecular fluorophores in the second near-infrared (NIR-II) window with long wavelength emission and high brightness, which can improve the performance of biological imaging. Herein, we report a molecular engineering approach to afford NIR-II fluorophores with these merits based on fused-ring acceptor (FRA) molecules. Dioctyl 3,4-propylenedioxy thiophene (PDOT-C8) is utilized as the bridging donor to replace 3-ethylhexyloxy thiophene (3-EHOT), leading to more than 20 times enhancement of brightness. The nanofluorophores (NFs) based on the optimized CPTIC-4F molecule exhibit an emission peak of 1,110 nm with a fluorescence quantum yield (QY) of 0.39% (QY of IR-26 is 0.050% in dichloroethane as reference) and peak absorption coefficient of 14.5 × 10⁴ M^-1·cm^-1 in aqueous solutions, which are significantly higher than those of 3-EHOT based COTIC-4F NFs. It is found that PDOT-C8 can weaken intermolecular aggregation, enhance protection of molecular backbone from water, and decrease backbone distortion, beneficial for the high brightness. Compared with indocyanine green with same injection dose, CPTIC-4F NFs show 10 times higher signal-to-background ratio for whole body vessels imaging at 1,300 nm long pass filters.