Defect Engineering of Bi2S3‐x@PDA/CuS Z‐Scheme Heterojunction for Enhanced Sonodynamic and Chemodynamic Cancer Therapy

Why It Matters

The platform overcomes the low ROS yield of conventional sonosensitizers and adds active tumor targeting, representing a scalable route to more effective, minimally invasive cancer treatments.

Key Takeaways

• Sulfur vacancies boost Bi2S3 charge separation.
• Z‑scheme BPC heterojunction integrates PDA and CuS.
• Generates singlet oxygen and hydroxyl radicals synergistically.
• HA coating provides tumor targeting and stability.
• In vivo results show significant tumor growth inhibition.

Pulse Analysis

Sonodynamic therapy (SDT) has emerged as a non‑invasive modality that relies on ultrasound‑triggered generation of reactive oxygen species (ROS) to kill cancer cells. Conventional sonosensitizers such as pristine Bi2S3 suffer from rapid electron‑hole recombination, limiting ROS quantum yield and therapeutic efficacy. Introducing sulfur vacancies creates defect states that act as charge traps, prolonging carrier lifetimes and facilitating intersystem crossing. This defect engineering strategy directly addresses the core limitation of SDT materials, positioning vacancy‑rich nanostructures as next‑generation sonosensitizers.

The BPC nanocomposite leverages a Z‑scheme heterojunction architecture, where Bi2S3‑x@PDA serves as a visible‑light absorber and CuS provides a complementary band alignment. Polydopamine (PDA) not only improves biocompatibility but also mediates efficient electron transfer between the two semiconductors, establishing a cascade that separates electrons and holes more effectively than single‑component systems. The exposed CuS sites act as a Fenton‑like nanozyme, converting endogenous H2O2 into highly toxic •OH radicals, while ultrasound‑excited holes consume glutathione, dismantling the tumor’s antioxidant defenses. This dual ROS production amplifies oxidative stress beyond what either SDT or chemodynamic therapy could achieve alone.

Surface grafting with hyaluronic acid (HA) imparts physiological stability and active targeting to CD44‑overexpressing cancer cells, enhancing tumor accumulation and minimizing off‑target effects. In vivo studies demonstrate that BPC@HA markedly suppresses tumor growth and enables NIR‑II photoacoustic imaging for real‑time monitoring. By integrating defect engineering, Z‑scheme charge management, and bio‑functionalization, this platform exemplifies a translational pathway for nanomedicines that can overcome intrinsic material constraints and the hostile tumor microenvironment, potentially reshaping the commercial landscape of precision oncology.