Hydrogel-based drug supply represents more and more acknowledged platforms for most cancers immunotherapy, largely on account of their potential to deal with important shortcomings of intravenous systemic supply [1], [2]. Their inherent capability for localized and sustained launch of immunomodulatory brokers maintains elevated drug concentrations inside tumor or post-resection websites, whereas considerably lowering off-target toxicities [3]. Moreover, the engineerable bodily and biochemical properties of hydrogels allow the design of immunologically favorable native microenvironments [4]. These engineered niches can reverse immunosuppression, promote immune cell recruitment and activation, and function localized reservoirs for antigens and adjuvants [5], [6]. Past passive drug transport, such multifunctional programmability allows hydrogels to behave as energetic and instructive scaffolds that reprogram the tumor immune microenvironment, thereby fostering a sustained systemic antitumor immune response [7].
Native drug supply affords inherent benefits for subcutaneous LN activation [8]. Proof demonstrated that subcutaneous administration of anti-PD1 reveals superior LN focusing on functionality in comparison with intravenous injection, thereby eliciting a stronger immune response [9]. Moreover, these nanoscale immunotherapeutic brokers leverage each passive focusing on by way of dimension results and energetic focusing on by way of ligand-receptor interactions, demonstrating sturdy LN or spleen-targeting capability to stimulate immune activation [10], [11]. To stop fast clearance of subcutaneously injected immunotherapeutic brokers, subcutaneous supply programs based mostly on injectable hydrogels have been extensively investigated. The distinctive physicochemical properties of hydrogels, reminiscent of porosity, stiffness, and degradation kinetics, will be tailor-made to control mobile infiltration and drug launch. Furthermore, they’ll function versatile depots for the spatiotemporally managed co-delivery of assorted therapeutic cargoes, together with cells, proteins, and nucleic acids [1], [12], [13], [14], [15]. Subsequently, creating hydrogel-based most cancers vaccines that induce T cell-mediated antitumor immunity within the draining LN is important for potent most cancers immunotherapy.
To bridge this hole, we engineered an injectable collagen-based hydrogel vaccine co-encapsulating personalised hybrid membrane vesicles and a recombinant anti-PD-1/IL-2 fusion protein (HM@FP Gel). This technique was designed as an built-in, instructionally energetic platform for localized immune reprogramming. We first characterised its structural integrity, shear-thinning rheology, and sustained launch profile in vitro. Practical evaluation confirmed that the gel potently activated dendritic cells (DCs) and, following subcutaneous administration, achieved extended retention and focused accumulation of its payload inside draining LNs. Within the MC38 colon carcinoma mannequin, administration of HM@FP Gel considerably suppressed native recurrence and triggered a potent systemic antitumor response. Transcriptomic profiling coupled with immunofluorescence imaging demonstrated that the gel actively reworked the draining LNs into organized, immunologically energetic hubs in mice, thereby elucidating the underlying mechanism in restoring LN-dependent antitumor immunity.
