NIR‐II Emissive Oligonucleotides Grafted π‐Conjugated Polymers for Low‐Temperature Photothermal and Gene Combined Therapy

Abstract In order to address the strong hydrophobicity and function limitation of NIR‐II emissive phototheranostic π‐conjugated polymers (CPs), appropriate modifications are necessary to impart water dispersibility and functionality to CPs. This study uses DNA as the hydrophilic and functional unit to modify CPs, synthesizing CP‐g‐DNA amphiphilic copolymers and producing water‐dispersible oligonucleotide‐modified π‐conjugated polymer nanoparticles (OCPNs) by self‐assembly. In addition to DNA′s gene regulation abilities that can combine with the low‐temperature photothermal therapy of CPs for enhanced tumor therapy, OCPNs display unique characteristics as novel nanomaterials. On one side, DNA changes the π–π interactions and results in a two‐fold enhancement in NIR‐II fluorescence emission, which greatly benefits tumor imaging. On the other side, DNA varies the surface properties of OCPNs and the nano‐bio interactions. OCPNs exhibit multiple cellular internalization pathways, including caveolae/lipid raft‐mediated uptake for cytoplasm delivery, which may enhance gene transfection combined with the photothermal‐promoted lysosome escape. Moreover, OCPNs can quickly accumulate in tumors due to their higher tissue penetration capability. Taken together, a strategy of using DNA to enable and advance the phototheranostic applications of CPs has been demonstrated, and the distinct properties of OCPNs will open up new biological application opportunities in the future.