Chemically engineering cells for precision medicine.

Cell-based therapy holds great potential to address unmet medical needs and revolutionize the healthcare industry, as demonstrated by several therapeutics such as CAR-T cell therapy and stem cell transplantation that have achieved great success clinically. Nevertheless, natural cells are often restricted by their unsatisfactory trafficking and lack of therapeutic payloads. Chemical engineering offers a cost-effective, easy-to-implement engineering tool that allows for strengthening the inherent favorable features of cells and confers them new functionalities.

Harnessing DNA for immunotherapy: Cancer, infectious diseases, and beyond.

Despite the rapid development of immunotherapy, low response rates, poor therapeutic outcomes and severe side effects still limit their implementation, making the augmentation of immunotherapy an important goal for current research. DNA, which has principally been recognized for its functions of encoding genetic information, has recently attracted research interest due to its emerging role in immune modulation. Inspired by the intrinsic DNA-sensing signaling that triggers the host defense in response to foreign DNA, DNA or nucleic acid-based immune stimulators have been used in the prevention and treatment of various diseases.

Enhancing Gasdermin-induced tumor pyroptosis through preventing ESCRT-dependent cell membrane repair augments antitumor immune response.

Pore-forming Gasdermin protein-induced pyroptosis in tumor cells promotes anti-tumor immune response through the release of pro-inflammatory cytokines and immunogenic substances after cell rupture. However, endosomal sorting complexes required for transport (ESCRT) III-mediated cell membrane repair significantly diminishes the tumor cell pyroptosis by repairing and subsequently removing gasdermin pores. Here, we show that blocking calcium influx-triggered ESCRT III-dependent membrane repair through a biodegradable nanoparticle-mediated sustained release of calcium chelator (EI-NP) strongly enhances the intracellularly delivered GSDMD-induced tumor pyroptosis via a bacteria-based delivery system (VNP-GD).

Depletion of tumor associated macrophages enhances local and systemic platelet-mediated anti-PD-1 delivery for post-surgery tumor recurrence treatment.

Immunosuppressive cells residing in the tumor microenvironment, especially tumor associated macrophages (TAMs), hinder the infiltration and activation of T cells, limiting the anti-cancer outcomes of immune checkpoint blockade. Here, we report a biocompatible alginate-based hydrogel loaded with Pexidartinib (PLX)-encapsulated nanoparticles that gradually release PLX at the tumor site to block colony-stimulating factor 1 receptors (CSF1R) for depleting TAMs. The controlled TAM depletion creates a favorable milieu for facilitating local and systemic delivery of anti-programmed cell death protein 1 (aPD-1) antibody-conjugated platelets to inhibit post-surgery tumor recurrence.