Sonodynamic therapy (SDT) has been explored for cancer therapy, especially for deep tumors due to its low tissue penetration restriction. The therapeutic efficacy of SDT is limited due to the complicated tumor microenvironment. This study reports the construction of oxygen‐carrying semiconducting polymer nanoprodrugs (OSPN_pro) for deep tumor treatment via combining amplified SDT with pyroptosis. An oxygen carrier perfluorohexane, sonodynamic semiconducting polymer as the sonosensitizer, and reactive oxygen species (ROS)‐responsive prodrug are co‐loaded into a nanoparticle system, leading to the formation of these polymer nanoprodrugs. Such OSPN_pro show an effective accumulation in tumor tissues after systemic administration, in which they deliver oxygen to relieve tumor hypoxia microenvironment and thus mediate amplified SDT via producing ROS under ultrasound (US) irradiation, even when the tumors are covered with a 2‐cm chicken breast tissue. In addition, the ROS‐responsive prodrugs are activated by the generated ROS to trigger pyroptosis of tumor cells. Such a sono‐pyroptosis induces a strong antitumor immunity with obviously higher level infiltrations of effector immune cells into tumors. Therefore, OSPN_pro‐based combinational therapy can greatly inhibit the growth of 2‐cm chicken breast tissue‐covered deep tumors and suppress tumor metastasis. This study offers a prodrug nanoplatform for treatment of deep tumor via sono‐pyroptosis strategy.

Photothermal therapy (PTT) has attracted broad attention as a promising method for cancer therapy with less severe side effects than conventional radiation therapy, chemotherapy and surgical resection. PTT relies on the photoconversion capacity of photothermal agents (PTAs), and a wide variety of nanomaterials have been employed as PTAs for cancer therapy due to their excellent photothermal properties. The PTAs are systematically or locally administered and become enriched in cancer cells to increase ablation efficiency. In recent years, PTAs and three-dimensional scaffolds have been hybridized to realize the local delivery of PTAs for the repeated ablation of cancer cells. Meanwhile, the composite scaffolds can stimulate the reconstruction and regeneration of the functional tissues and organs after ablation of cancer cells. A variety of composite scaffolds of photothermal nanomaterials have been prepared to combine the advantages of different modalities to maximize their therapeutic efficacy with minimal side effects. The synergistic effects make the composite scaffolds attractive for biomedical applications. This review summarizes these latest advances and discusses the future prospects. Graphical abstract