Rational Design of New Biocompatible Near-Infrared Conjugated Polymer Nanoparticles for Biomedical Applications

Conjugated polymer nanoparticles (CPNs) have gained significant attention as promising nanomaterials for cancer theranostics, particularly in fluorescence imaging and therapy, where early detection and image-guided surgery are crucial for effective treatment. Despite growing interest, there remains a notable gap in the literature regarding rational design strategies and clear structure-property relationships for CPN development. Comprehensive design rules that guide the production of CPNs with optimized performance are still lacking, hindering the systematic advancement of this field. Addressing this gap, we synthesized a series of new donor-acceptor (D-A) conjugated polymers (CPs), each incorporating a common acceptor unit paired with three distinct donor groups to assess their impact on optical and biological properties. The resulting nanoparticles exhibited excellent characteristics as fluorescent contrast agents, including enhanced fluorescence intensity in aqueous media along with favorable photostability. Studies using human colorectal carcinoma (HCT-116) and human umbilical vein endothelial cells (HUVEC) confirmed the CPNs' nontoxic nature, strong fluorescence, and biocompatibility. Notably, this study is the first to investigate the cellular uptake mechanism of CPNs in HCT-116 cells, offering valuable insights into their biological interactions. These findings not only demonstrate the potential of these newly developed CPNs for fluorescence imaging of HCT-116 but also underscore the urgent need for rational design frameworks to guide the future development of next-generation CPNs.