Conjugated Oligomer‐Directed Formation of Hollow Nanoparticles for Targeted Photokilling Cancer Cells under Hypoxia

Abstract Photodynamic therapy (PDT) has been recognized as one powerful solution to treat cancers, but its efficacy is often impaired by the oxygen‐deficient hypoxic tumor microenvironment. Herein, conjugated oligomer‐based hollow nanoparticles are developed as efficient phototheranostic agent for targeted PDT under hypoxia. The sialic acid (SA)‐imprinted hollow nanoparticles are facilely prepared via a nanoprecipitation method using a conjugated oligomer as photosensitizer and an amphiphilic polymer as matrix. The strong intra‐ and inter‐molecular π–π stacking interactions of the conjugated oligomer direct the self‐assembly and formation of hollow nanostructure. Triggered by 660 nm laser, the nanoparticles exhibit prominent reactive oxygen species (ROS) generation both in water and cellular medium, which are specifically determined as singlet oxygen (¹O₂) and superoxide radical (O₂^–•) under normoxia (20% O₂) while mainly O₂^–• under hypoxia (1% O₂). Moreover, the feature of SA‐imprinted surface makes these nanoparticles capable of selectively targeting and being internalized into SA over‐expressed cancer cells, and their efficient PDT behaviors in vitro are also demonstrated even under severely hypoxic environment. Thus, the work provides a promising photosensitizer candidate for targeted PDT in hypoxic tumor.