Nanocomposite pastes of gelatin and cyclodextrin-grafted chitosan nanoparticles as potential postoperative tumor therapy

Effective postoperative therapy is crucial for preventing tumor recurrence and metastasis. Nanocomposite (NC) pastes of Gel/CS-g-CD NP with unique viscoelastic properties and pH-responsive drug delivery ability were prepared from gelatin (Gel) and β-cyclodextrin-grafted chitosan nanoparticles (CS-g-CD NPs) through host–guest interactions between the aromatic amino acid residues of gelatin and β-cyclodextrin. The dynamic rheological properties, shear strength, and shear viscosity were modulated through variations in the concentration of CS-g-CD NPs in the NC pastes. Due to the reversibility of the host–guest interactions, the NC pastes exhibited shear-thinning and self-healing properties, endowing them with good injectability. Loading of doxorubicin (DOX) in the nanoparticles (DOX-CSCD NPs) forming the NC pastes of Gel/DOX-CSCD NP allowed pH-triggered DOX release in a simulated tumoral microenvironment, because of the labile nature of the CS-g-CD NPs under acidic conditions. In vitro experiments showed that the NC pastes of Gel/DOX-CSCD NP induced sustained tumor cell inhibition. Moreover, in vivo studies with tumor-bearing mice indicated that the NC pastes of Gel/DOX-CSCD NP can effectively inhibit tumor recurrence after surgical resection. Therefore, the NC pastes described in this work may act as an effective injectable drug delivery system for postoperative tumoral treatment.