The cyclic guanosine monophosphate‐adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signalling pathway has been a promising target for anticancer immunity, but rationally activating and enhancing this pathway in tumour cells is critical. Herein, a glutathione sensitive ZnFe₂O₄‐based nanosystem is developed to programmatically initiate and enhance the STING signalling pathway in tumour cells. The prepared ZnFe₂O₄ nanoparticles were coated with cancer cell membrane (CCM), which enabled the nanosystem target tumour cells. In tumour cells, ZnFe₂O₄ nanoparticles could be disintegrated by responding to high level glutathione, and the released Fe³⁺ generated reactive oxygen species to induce the DNA leakage into the cytoplasm to stimulate cGAS. Then Zn²⁺ promoted cGAS‐DNA phase separation to intensify the cGAS enzymatic activity. In addition, the low dose encapsulation of paclitaxel (PTX) acting as an antimitotic agent (ZnFe₂O₄‐PTX@CCM) ensured the sustained activation of cGAS/STING pathway. The in vitro and in vivo results confirmed that ZnFe₂O₄‐PTX@CCM elevated the cGAS/STING activity, promoted dendritic cell maturation, increased cytotoxic T lymphocyte and natural killer cells infiltration, eventually inhibiting the tumour progress and postoperative recurrence. This study provided feasible references on constructing STING activation nanosystem for tumour immunotherapy.

Peptides are one of the most important functional motifs for constructing smart drug delivery systems (DDSs). Functional peptides can be conjugated with drugs or carriers via covalent bonds, or assembled into DDSs via supramolecular forces, which enables the DDSs to acquire desired functions such as targeting and/or environmental responsiveness. In this mini review, we first introduce the different types of functional peptides that are commonly used for constructing DDSs, and we highlight representative strategies for designing smart DDSs by using functional peptides in the past few years. We also state the challenges of peptide-based DDSs and come up with prospects.