Certain chemotherapeutics and forms of ionizing radiation can induce immunogenic cell death (ICD). If there simultaneously exist immune adjuvants within the tumor, such antitumor immunity would be further amplified. However, as clinical chemo/radiotherapies are usually repeatedly given at low individual doses, it would be impractical to administrate immune adjuvants into tumors at each dose of chemo/radiotherapies. Thus, a smart hydrogel is developed that releases immune adjuvants in response to repeatedly applied chemo‐/radiotherapies. Herein, alginate is conjugated with an adenosine triphosphate (ATP)‐specific aptamer, which is hybridized with immunoadjuvant CpG oligonucleotide. Upon intratumoral injection, alginate‐based hydrogel is formed in situ. Interestingly, low doses of oxaliplatin or X‐rays, while inducing ICD of tumor cells, could trigger release of ATP, which competitively binds with ATP‐specific aptamer to trigger CpG release. Therefore, the smart hydrogel could release the immune adjuvant synchronized with low‐dose repeated chemo/radiotherapies, achieving remarkable synergistic responses in eliminating established tumors, as well as immune memory to reject re‐challenged tumors. Moreover, repeated radiotherapies assisted by the smart hydrogel could inhibit distant tumor metastases, especially in combination with immune checkpoint blockade. The study presents a conceptually new strategy to boost cancer immunotherapy coherent with repeated low‐dose chemo‐/radiotherapies following a clinically relevant manner.

Artificial antigen-presenting cells (aAPCs) constructed by integrating T cell activation ligands on biocompatible materials hold great potential in tumor immunotherapy. However, it remains challenging to develop aAPCs, which could mimic the characteristics of natural APCs, thereby realizing antigen-specific T cells activation in vivo. Here, we report the first effort to construct natural lymphocyte-based homologous targeting aAPCs (LC-aAPCs) with lipid-DNA-mediated noninvasive live cell surface engineering. Through a predesigned bottom-up self-assembly path, we achieved natural-APC-mimicking distribution of T cell activation ligands on LC-aAPCs, which would enable the optimized T cell activation. Moreover, the lipid-DNA-mediated self-assembly occurring on lipid bilayers would not affect the functions of homing receptors expressed on lymphocyte. Therefore, such LC-aAPCs could actively migrate to peripheral lymphatic organs and then effectively activate antigen-specific T cells. Combined with an immune checkpoint inhibitor, such LC-aAPCs could effectively inhibit the growth of different tumor models. Thus, our work provides a new design of aAPCs for in vivo applications in tumor immunotherapy, and the lipid-DNA-mediated noninvasive live cell surface engineering would be a powerful tool for designing cell-based therapeutics.

The development of nanomedicine systems for applications in cancer therapies has been widely explored in the last decade. With inherent biocompatibility, nanomedicine devices derived from biological membranes have shown many unique advantages compared with traditional artificial nanomaterials for biomedical applications. Herein, we present a comprehensive review of the recent development of cell membrane derived nanomedicines in cancer treatment. We firstly outline the advantages of biological membranes in nanomedicine design derived from their intrinsic characteristics, and then discuss the applications of biological membrane derived nanomedicines. For the first major category of membrane-derived nanomedicine, synthetic nanoparticles are usually camouflaged with cell membranes to acquire additional functionalities. The other type of membrane-based nanomedicine is directly using the engineered cell membrane-derived vesicles or nanovesicles secreted by cells for tumor treatment. At last, we discuss the challenges of membrane-derived nanomedicines towards future clinical applications, following with perspectives on possible solutions to the current problems.

Peptide vaccines have advantages in easy fabrication and high safety, but their effectiveness is hampered by the poor immunogenicity of the epitopes themselves. Herein, we constructed a series of framework nucleic acids (FNAs) with regulated rigidity and size to precisely organize epitopes in order to reveal the influence of epitope spacing and carrier rigidity on the efficiency of peptide vaccines. We found that assembling epitopes on rigid tetrahedral FNAs (tFNAs) with the appropriate size could efficiently enhance their immunogenicity. Further, by integrating epitopes from SARS‐CoV‐2 on preferred tFNAs, we constructed a COVID‐19 peptide vaccine which could induce high titers of IgG against the receptor binding domain (RBD) of SARS‐CoV‐2 spike protein and increase the ratio of memory B and T cells in mice. Considering the good biocompatibility of tFNAs, our research provides a new idea for developing efficient peptide vaccines against viruses and possibly other diseases.

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