Novel amphiphilic π-conjugated polymer nanoparticles tailored to efficiently absorb in the near-infrared II (NIR-II) region of the electromagnetic spectrum (>
1000 nm) are presented. To achieve this, it is statistically introduced triethylene glycol substituted bithiophene moieties in various contents into a polymer backbone consisting of alternating thiophene and [1,2,5]thiadiazolo[3,4-g]quinoxaline. Through systematic modifications of monomer ratios, four amphiphilic conjugated polymers are produced. The presence of hydrophilic side chain, like triethylene glycol monomethyl ether, enhanced the polymer's concentration in aqueous media of up to 470%, versus the D-A thiophene and [1,2,5]thiadiazolo[3,4-g]quinoxaline hydrophobic analog polymer, enabling the production of surfactant-free conjugated polymer nanoparticles (CPNs) with higher concentrations (20.3 ppm maximum). Subsequently, the impact of this structural fine-tuning on the optical properties of the polymers and their corresponding CPNs are meticulous investigated. In both cases, it is identified the minimum bithiophene content that maintained the absorption spectra above 1000 nm at significantly higher concentrations. So, these findings contribute to the extensive prospects of these materials in multiple fields including biomedical and optoelectronic applications.