Astragaloside IV microfibers assembling into injectable 3D-scaffolds with intrinsic immunoactivity for enhanced tumor vaccine efficacy

• Excipients-free Astragaloside IV microfibers (SMF) was firstly reported. • SMF was injectable and has intrinsic immunoactivity. • SMF could be assembled into 3D-Scaffolds to recruit and program immune cells. • Scaffold vaccines are simply based on the mixture of SMF and tumor lysates. • SMF scaffolds boost antitumor immunity against different tumor models. Injectable scaffold tumor vaccines have emerged as an effective strategy to boost cancer immunotherapy. To minimize the reliance on expensive and diverse immunostimulatory drugs, innovative bioactive scaffolds with both biocompatibility and intrinsic immunostimulatory capabilities are highly desired. Here we demonstrate that Astragaloside IV (AS-IV), the principal bioactive component of the traditional Chinese herb Huangqi can be fabricated as mesoporous and excipients-free microfibers (SMF). SMF are injectable and can spontaneously assemble in vivo to form scaffolds with macroporous 3D structures, recruiting substantial numbers of dendritic cells (DCs) to the macropores between the packed fibers and leading to enhanced DCs maturation through an NLRP3 pathway. Without loading toxic/expensive immunostimulating drugs, AS-IV-based scaffold vaccine demonstrates impressive immunostimulatory activity and provokes efficient antitumor immunity in melanoma and breast cancer tumor models. Moreover, the resultant scaffolds can synergize well with clinically used TLR-4 agonists and immune checkpoint blockade to achieve enhanced antitumor efficacy. Materials advances in this study enable new pharmaceutical formulations as injectable bioactive scaffolds with intrinsic immunomodulating capability and suggest their great application potential in constructing safe and efficient tumor vaccines.