Recent advances and applications of semiconducting polymer nanomaterials in cancer therapy

In the era of precision medicine for cancer treatment, the rational design of nanoparticles with responsive characteristics is crucial for the release of payloads at target sites. At tumor sites, internal triggers such as pH, enzymes, and redox conditions are often used to activate drugs. However, some internal triggers may vary due to pathological conditions and might be insufficient to effectively activate nanoparticles. Additionally, these internal triggers can also be activated in normal tissues, which motivates the design of therapeutic agents that respond to external stimuli. Compared to endogenous stimuli, external stimuli such as light, ultrasound, and X-rays offer greater flexibility, enabling controlled drug delivery in a specific and precise manner and providing an ideal approach to reduce systemic toxicity. Semiconducting polymer nanoparticles (SPNs), derived from π-conjugated polymers, possess optical, chemical, and biological properties, allowing them to efficiently convert near-infrared (NIR) light, ultrasound, and X-ray energy into heat or singlet oxygen ( 1 O 2 ), thereby inducing immunogenic therapy. By covalently conjugating SPNs with therapeutic agents, 1 O 2 -activatable SPN-based therapeutic agents can be constructed to achieve targeted delivery and on-demand release of therapeutics. Here, we summarize recent advancements in SPNs based nanomedicines stimulated by NIR light, ultrasound, and X-rays for photothermal therapy (PTT), photodynamic therapy (PDT), sonodynamic therapy (SDT), and radiodynamic therapy (RDT) in cancer treatment. We discuss in detail the combination therapies achieved by loading or conjugating SPNs with other therapeutic elements, such as chemotherapeutic drugs and immunotherapeutic agents. Furthermore, we address the potential challenges and clinical translation prospects of SPNs in biomedical applications. • This review covers recent advances in cancer therapy using semiconducting polymer nanoparticles (SPNs) • This review focuses on engineering strategies of SPNs for precise cancer therapy via controllable spatiotemporal properties. • This review provides new ideas for designing external stimuli responsive nanosystems and inspires their future biomedical applications.