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

초록

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.

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