In this context, we developed a drug-bearing supramolecular hydrogel system to intratumourally (i.t.) deliver CDNs against malignant tumours to achieve cancer chemoimmunotherapy. Our strategy was to chemically conjugate the hydrophilic pep-tide moiety iRGD (a tumour-penetrating peptide that can bind to neuropilin-1 (NRP-1) and trigger tumour tissue penetration) to the hydrophobic anticancer drug CPT to form a self-assembling and self-formulating peptide-drug conjugate (diCPT-iRGD). In aqueous solution, the designed drug amphiphile spontaneously assembles into supramolecular nanotubes (NTs). The negatively charged STING agonist (c-di-AMP (CDA)) can condense on the surface of these positively charged NTs through electrostatic complexations. After injection into the tumour site, the CDA-NT solution can immediately form a hydrogel, functioning as a local reservoir for extended localized release of CDA and CPT to awaken both the innate and adaptive immune systems.

In this context, we developed a drug-bearing supramolecular hydrogel system to intratumourally (i.t.) deliver CDNs against malignant tumours to achieve cancer chemoimmunotherapy. Our strategy was to chemically conjugate the hydrophilic pep-tide moiety iRGD (a tumour-penetrating peptide that can bind to neuropilin-1 (NRP-1) and trigger tumour tissue penetration) to the hydrophobic anticancer drug CPT to form a self-assembling and self-formulating peptide-drug conjugate (diCPT-iRGD). In aqueous solution, the designed drug amphiphile spontaneously assembles into supramolecular nanotubes (NTs). The negatively charged STING agonist (c-di-AMP (CDA)) can condense on the surface of these positively charged NTs through electrostatic complexations. After injection into the tumour site, the CDA-NT solution can immediately form a hydrogel, functioning as a local reservoir for extended localized release of CDA and CPT to awaken both the innate and adaptive immune systems.