Hejin Jiang

Precise intracellular delivery remains a critical barrier to the efficacy of therapeutic biomolecules. Coacervates, with their high loading capacity, have emerged as a transformative drug delivery platform that can facilitate the intracellular delivery of diverse therapeutic cargos but are limited by poor stability, nonspecific cellular internalization, and uncontrolled release. Herein, we report a simple and versatile surface-engineering strategy that improves the stability of coacervates and enables programmable cell targeting and precise intracellular delivery. Peptide coacervates (PCs) designed with programmable release were coated with polyphenol–peptide networks (PC@PPNs) to encapsulate diverse cargos, including fluorophores, toxic proteins, pro-apoptotic peptides, and plasmid DNA. The dual pH- and glutathione-responsive disassembly of PC@PPNs facilitates endosomal escape and enables controlled cytosolic release. Notably, the association of PC@PPNs with specific cells can be readily programmed by modulating the peptide sequence on PPNs. For example, incorporating HER2-targeting peptides increases the specific association of PC@PPNs with SKOV3 cells from 14% to 75%. The cell-specific targeting is further validated in vivo, as demonstrated by a pronounced size reduction in HER2-overexpressing tumors. This work establishes a rational framework for engineering functional coacervates, advancing their development as versatile and programmable platforms for intracellular delivery.

Providing oxygen and preventing infection at wound sites are effective ways to heal diabetic chronic wounds. Inspired by natural lichens, a bioprinted biogenic hydrogel (BBH) containing microalgae and probiotics is developed for diabetic chronic wound therapeutics, which offers prolonged biogenetic oxygen supply by microalgae and infection inhibition by probiotics. The rational design of symbiotic BBH with customizable structure and microorganism composition enhances wound resilience against elevated glucose levels and hypoxia, leading to the increased migration ability of fibroblasts and the angiogenic potential of human umbilical vein endothelial cells. Notably, BBH‐treated diabetic wounds exhibit dense vascular distribution, reduced hypoxia levels and inflammatory responses, and enhanced epithelial differentiation and keratinization abilities. Consequently, the BBH achieves rapid tissue repairing within 3 d and restores approximately 90% of the whole skin structure within 12 d. This work presents an engineered platform for regulating biological microenvironment of diabetic wounds and provides insights for developing bioprinted hybrid microorganism systems.

Bacteria can colonize a variety of in vivo biointerfaces, particularly the skin, nasal, and oral mucosa, the gastrointestinal tract, and the reproductive tract, but also target specific lesion sites, such as tumor and wound. By virtue of their prominent characteristics in motility, editability, and targeting ability, bacteria carrying imageable agents are widely developed as living probes for bioimaging and diagnosis of different diseases. This review first introduces the strategies used for preparing bacteria‐based living probes, including biological engineering, chemical modification, intracellular loading, and optical manipulation. It then summarizes the recent progress of these living probes for fluorescence imaging, near‐infrared imaging, ultrasonic imaging, photoacoustic imaging, magnetic resonance imaging, and positron emission tomography imaging. The biomedical applications of bacteria‐based living probes are also reviewed particularly in the bioimaging and diagnosis of bacterial infections, cancers, and intestine‐associated diseases. In addition, the advantages and challenges of bacteria‐based living probes are discussed and future perspectives are also proposed. This review provides an updated overview of bacteria‐based living probes, highlighting their great potential as a unique yet versatile platform for developing next‐generation imageable agents for intelligent bioimaging, diagnosis, and even therapy.

Chirality is ubiquitous in biological systems, which is closely related to biological functions, life processes, and even the pathogenesis of diseases. However, the interface between the chirality of synthetic materials and organisms, particularly the immune system, remains poorly understood. Here, supramolecular chiral polymer micelles (SCPMs) are prepared by complexing antigenic proteins with chiral amino acid‐modified polyethyleneimine. The introduction of chirality not only reduces the toxicity of cationic polymer, but also benefits cell uptake and antigen presentation. Especially, D‐chirality presents the lowest cytotoxicity, while promoting the highest expression level of costimulatory molecules on dendritic cells compared to L‐chirality and achirality. The superiority of D‐chirality to stimulate dendritic cell maturation is supported by immunization with D‐SCPMs, which achieves significant antigen‐specific proliferation of T cells in the spleen, lymph nodes, and tumor of mice. Chirality‐mediated antigen processing and presentation are demonstrated by D‐SCPMs self‐assembled from chiral alkaline histidine or neutral phenylalanine modified polyethyleneimine and tumor associated ovalbumin or severe acute respiratory syndrome coronavirus 2 spike 1 antigenic protein. Immunoactivation enabled by D‐chirality opens a window to prepare potent nanotherapeutics for disease prevention and treatment.