Calcium‐overload cancer therapy has gained more and more attention owing to its good therapeutic efficacy with low side effect. However, conventional calcium‐overload therapy is achieved by introducing an additional calcium element into the tumor site by nanomedicines, which may also lead to the calcium‐overload of normal organs, causing an undesirable side effect. To address such issues, capsaicin‐decorated semiconducting polymer nanoparticles (CSPN) are designed to modulate the calcium ion channel of cancer cells for calcium‐overload cancer therapy without adding an additional calcium element. CSPN is composed of a near‐infrared (NIR) absorbing semiconducting polymer (SP) PCPDTBT and a capsaicin‐conjugated amphiphilic copolymer, PEG‐PHEMA‐Cap. Under NIR laser irradiation, PCPDTBT can generate singlet oxygen (1O2), which not only triggers the release of capsaicin, but also induces photodynamic therapy (PDT). The released capsaicin can further activate transient receptor potential cation channel subfamily V member 1 (TRPV1) of U373 cancer cells, leading to an influx of calcium ions into cells. In addition, the intense NIR‐II fluorescence signal of CSPN makes it suitable for tumor imaging. Thus, this study develops a tumor specific nanotheranostic system for NIR‐II fluorescence imaging‐guided calcium‐overload/PDT combination therapy.

Second near-infrared window fluorescence imaging (NIR-II FI) has attracted tremendous attention in bioimaging. Until now, most probes for NIR-II FI are nanomaterials that are metabolized via hepatobiliary metabolism. Such a metabolic pathway may take several months, causing long-term toxicity. Herein, we design and synthesize a renal-clearable PEGylated semiconducting oligomer (PSO) for the NIR-II FI of tumor. PSO is composed of a semiconducting oligomer (SO) backbone as an NIR-II fluorescence reporter and four poly­(ethylene glycol) (PEG) side chains as water-soluble enhancers. PSO can emit an NIR-II fluorescence signal with the maximum emission at 1000 nm under the excitation of 808 nm light. PSO shows good biocompatibility and can be partially cleared out of body via renal clearance. PSO can be utilized for the NIR-II FI of tumor as it can effectively accumulate into tumor.

Photoacoustic (PA) imaging in the second near-infrared (NIR-II) window has gained more and more attention in recent years and showed great potential in the field of bioimaging. Until now, numerous materials have been developed as contrast agents for NIR-II PA imaging. Among them, small molecule dyes hold unique advantages such as definite structures and capability of fast clearance from body. By virtue of these advantages, small molecule dyes-constructed nanoparticles have relatively small size and show promise in the clinical translation. Thus, in this minireview, we summarize recent advances in small molecule dyes-based nanotheranostics for NIR-II PA imaging and cancer therapy. Studies about NIR-II PA imaging-guided phototherapy are first introduced. Then, NIR-II PA imaging-guided phototherapy-based combination therapeutic systems are reviewed. Finally, the conclusion and perspectives of this field are summarized and discussed.