Multi-bioinspired Sprayable Nanotherapeutics for Tumor-Specific Focal Cancer Therapy

Chemotherapy is commonly used to treat cancer. However, insufficient retention at the target site and systemic toxicity remains critical challenges. Chitosan has attracted considerable attention as a carrier backbone for delivering therapeutic cargos because of its biocompatibility and mucoadhesive property. However, pH and concentration-dependent solubility of chitosan has been restricted further applications to clinical settings. Inspired by marine mussels and crustaceans, in this study, we present chitosan-based nanoparticles containing catechol–Fe³⁺ complexes (Cat-CS NPs) as a tumor-activatable delivery system to achieve highly efficient locoregional treatment of cancer via a simple spray process while minimizing adverse effects towards surrounding normal tissues. Cat-CS NPs were fabricated through electrospraying and exhibited superior adhesiveness on substrates in aqueous conditions in a surface-independent manner. The pH-responsive stoichiometry of catechol–Fe³⁺ coordination in doxorubicin (DOX)-loaded Cat-CS NPs (Cat-CS@DOX NPs) enabled a triggered release of DOX in response to acidic conditions around tumor tissues. The sprayed Cat-CS@DOX NPs significantly inhibited cancer cell growth in vitro while exhibiting good biocompatibility towards normal cells. Taken together, Cat-CS NP-based sprayable nanotherapeutics can be used as a locoregional delivery system, especially in adjuvant cancer therapy.