Single-walled carbon nanohorns-based smart nanotheranostic: From phototherapy to enzyme-activated fluorescence imaging-guided photodynamic therapy.

Phototheranostics, a local non-invasive approach that integrates light-based diagnostics and therapeutics, enables precise treatment using nanotheranostic agents with minimal damage to normal tissues. However, ensuring high-efficiency ablation of cancer cells using phototheranostics for one time irradiation is highly challenging. Herein, we designed and synthesized a single-walled carbon nanohorns-based nanotheranostic agent, HA-IR808-SWNHs, by loading IR808, a photosensitizer, conjugated hyaluronic acid (HA) with an amide bond on the surface of single-walled carbon nanohorns (SWNHs) through noncovalent π-π interaction by the sonication method. The HA in HA-IR808-SWNHs improves the water dispersibility of SWNHs and endows SWNHs with targeting capabilities. Importantly, overexpressed endogenous hyaluronidase in cancer cells actively disassembles HA-IR808-SWNHs, forming small HA-IR808 fragments. The fragments exhibit a strong fluorescence signal and can be used to guide programmed photodynamic therapy for sequentially eliminating the residual living cancer cells. The current study confirms that HA-IR808-SWNHs is an endogenous enzyme-responsive nanotheranostic agent that can be employed to precisely track and ablate residual cancer cells in a spatiotemporal manner. The results strengthen the understanding of SWNH functionalization and expand its potential biomedical application, especially in cancer theranostics.