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Immunological adjuvants are essential for successful cancer vaccination. However, traditional adjuvants have some limitations, such as lack of controllability and induction of systemic toxicity, which restrict their broad application. Here, we present a light-activable immunological adjuvant (LIA), which is composed of a hypoxia-responsive amphiphilic dendrimer nanoparticle loaded with chlorin e6. Under irradiation with near-infrared light, the LIA not only induces tumour cell lysis and tumour antigen release, but also promotes the structural transformation of 2-nitroimidazole containing dendrimer to 2-aminoimidazole containing dendrimer which can activate dendritic cells via the Toll-like receptor 7-mediated signaling pathway. The LIA efficiently inhibits both primary and abscopal tumour growth and induces strong antigen-specific immune memory effect to prevent tumour metastasis and recurrence in vivo. Furthermore, LIA localizes the immunological adjuvant effect at the tumour site. We demonstrate this light-activable immunological adjuvant offers a safe and potent platform for in situ cancer vaccination. Immunological adjuvants are a crucial component of cancer vaccines. Here the authors design a light-activable immunological adjuvant, based on hypoxia-responsive amphiphilic dendrimer nanoparticles loaded with a photodynamic agent, promoting anti-tumor immune responses in preclinical cancer models.

New strategies with high antimicrobial efficacy against multidrug-resistant bacteria are urgently desired. Herein, we describe a smart triple-functional nanostructure, namely TRIDENT (Thermo-Responsive-Inspired Drug-Delivery Nano-Transporter), for reliable bacterial eradication. The robust antibacterial effectiveness is attributed to the integrated fluorescence monitoring and synergistic chemo-photothermal killing. We notice that temperature rises generated by near-infrared irradiation did not only melt the nanotransporter via a phase change mechanism, but also irreversibly damaged bacterial membranes to facilitate imipenem permeation, thus interfering with cell wall biosynthesis and eventually leading to rapid bacterial death. Both in vitro and in vivo evidence demonstrate that even low doses of imipenem-encapsulated TRIDENT could eradicate clinical methicillin-resistant Staphylococcus aureus , whereas imipenem alone had limited effect. Due to rapid recovery of infected sites and good biosafety we envision a universal antimicrobial platform to fight against multidrug-resistant or extremely drug-resistant bacteria. Antibiotic resistance is a major global health challenge. Here, the authors report on a thermoresponsive delivery system for combined photothermal and antibiotic delivery with fluorescent tracking abilities and demonstrate application against antibiotic resistant bacteria in vitro and in vivo.

Cancer vaccines hold great promise for improved cancer treatment. However, endosomal trapping and low immunogenicity of tumour antigens usually limit the efficiency of vaccination strategies. Here, we present a proton-driven nanotransformer-based vaccine, comprising a polymer–peptide conjugate-based nanotransformer and loaded antigenic peptide. The nanotransformer-based vaccine induces a strong immune response without substantial systemic toxicity. In the acidic endosomal environment, the nanotransformer-based vaccine undergoes a dramatic morphological change from nanospheres (about 100 nanometres in diameter) into nanosheets (several micrometres in length or width), which mechanically disrupts the endosomal membrane and directly delivers the antigenic peptide into the cytoplasm. The re-assembled nanosheets also boost tumour immunity via activation of specific inflammation pathways. The nanotransformer-based vaccine effectively inhibits tumour growth in the B16F10-OVA and human papilloma virus-E6/E7 tumour models in mice. Moreover, combining the nanotransformer-based vaccine with anti-PD-L1 antibodies results in over 83 days of survival and in about half of the mice produces complete tumour regression in the B16F10 model. This proton-driven transformable nanovaccine offers a robust and safe strategy for cancer immunotherapy.A shape-changing pH-responsive cancer vaccine delivers antigenic peptides directly to the cytoplasm and boosts the cellular immune response upon activation of the inflammasome pathway, efficiently inhibiting tumour growth and extending survival in animal tumour models.

Over centuries of clinical practice, Chinese herbal medicines (CHMs) have gained widespread recognition for their efficacy in treating various diseases. However, their complex material basis and relatively mild therapeutic efficacy limit their modernization and quality control. Recently, the application of pharmaceutical nanotechnology to CHMs has not only enhanced their efficacy, but also helped elucidate their material basis, thereby substantially advancing their modernization. Nano‐modified CHMs have shown improvements in multiple aspects, such as bioavailability, targeting ability, toxicity reduction, and sustained release. In this review, nano‐strategies for emerging, revolutionary, and promising pathways for modernizing CHMs are revealed. First, the development, application potential, particularities, and limitations of CHMs are reviewed. Subsequently, a systematic and comprehensive analysis of the two nano‐strategies for optimizing CHMs are presented, highlighting the distinct characteristics of the carrier‐free and carrier‐based approaches. The specific advantages of these strategies, including improved bioavailability, increased targeting ability, reduced toxicity, and controlled release, are discussed. The novel research directions resulting from the application of pharmaceutical nanotechnology to CHMs are also explored, such as elucidating CHM treatment theories, combining traditional Chinese medicine topical therapies, drug screening, and expanding innovative drug formulations. Finally, the challenges and opportunities in this field are addressed to inspire future research. This review offers a comprehensive overview of pharmaceutical nanotechnology strategies to address limitations associated with the complex material basis and relative mild therapeutic efficacy of Chinese herbal medicines, and summarizes the advantages of these strategies. In addition, it also concludes with recommendations for future challenges and developments in this field.

Diffuse intrinsic pontine glioma (DIPG) is a rare and fatal pediatric brain tumor. Mutation of p53‐induced protein phosphatase 1 (PPM1D) in DIPG cells promotes tumor cell proliferation, and inhibition of PPM1D expression in DIPG cells with PPM1D mutation effectively reduces the proliferation activity of tumor cells. Panobinostat effectively kills DIPG tumor cells, but its systemic toxicity and low blood–brain barrier (BBB) permeability limits its application. In this paper, a nano drug delivery system based on functionalized macrophage exosomes with panobinostat and PPM1D‐siRNA for targeted therapy of DIPG with PPM1D mutation is prepared. The nano drug delivery system has higher drug delivery efficiency and better therapeutic effect than free drugs. In vivo and in vitro experimental results show that the nano drug delivery system can deliver panobinostat and siRNA across the BBB and achieve a targeted killing effect of DIPG tumor cells, resulting in the prolonged survival of orthotopic DIPG mice. This study provides new ideas for the delivery of small molecule drugs and gene drugs for DIPG therapy. Functionalized macrophage exosomes with panobinostat and PPM1D‐siRNA are constructed for targeted therapy of diffuse intrinsic pontine glioma (DIPG) with PPM1D mutation. The nano drug delivery system can deliver panobinostat and siRNA across the blood–brain barrier and achieve a targeted killing effect of DIPG tumor cells, resulting in the prolonged survival of orthotopic DIPG mice.

Patients with triple‐negative breast cancer (TNBC) have the worst clinical outcomes when compared to other subtypes of breast cancer. Nanotechnology‐assisted photothermal therapy (PTT) opens new opportunities for precise cancer treatment. However, thermoresistance caused by PTT, as well as uncertainty in the physiological metabolism of existing phototherapeutic nanoformulations, severely limit their clinical applications. Herein, based on the clinically chemotherapeutic drug mitoxantrone (MTO), a multifunctional nanoplatform (MTO‐micelles) is developed to realize mutually synergistic mild‐photothermal chemotherapy. MTO with excellent near‐infrared absorption (≈669 nm) can function not only as a chemotherapeutic agent but also as a photothermal transduction agent with elevated photothermal conversion efficacy (ƞ = 54.62%). MTO‐micelles can accumulate at the tumor site through the enhanced permeability and retention effect. Following local near‐infrared irradiation, mild hyperthermia (<50 °C) assists MTO in binding tumor cell DNA, resulting in chemotherapeutic sensitization. In addition, downregulation of heat shock protein 70 (HSP70) expression due to enhanced DNA damage can in turn weaken tumor thermoresistance, boosting the efficacy of mild PTT. Both in vitro and in vivo studies indicate that MTO‐micelles possess excellent synergetic tumor inhibition effects. Therefore, the mild‐photothermal chemotherapy strategy based on MTO‐micelles has a promising prospect in the clinical transformation of TNBC treatment. A multifunctional drug delivery system (MTO‐micelles) based on the chemotherapeutic drug mitoxantrone (MTO) and amphiphilic polymer DSPE‐PEG2000 is developed. MTO induced DNA damage amplify the effect of Mild‐photothermal Chemotherapy by downregulating HSP70 expression. This mild‐photothermal chemotherapeutic formulation provides a facile and effective way for the TNBC treatment.

Traditional Chinese medicine (TCM) is widely used in clinical practice, including skin and gastrointestinal diseases. Here, a potential TCM QY305 (T‐QY305) is reported that can modulate the recruitment of neutrophil in skin and colon tissue thus reducing cutaneous adverse reaction and diarrhea induced by epidermal growth factor receptor inhibitors (EGFRIs). On another hand, the T‐QY305 formula, through regulating neutrophil recruitment features would highlight the presence of N‐QY305, a subunit nanostructure contained in T‐QY305, and confirm its role as potentially being the biomaterial conferring to T‐QY305 its pharmacodynamic features. Here, the clinical records of two patients are analyzed expressing cutaneous adverse reaction and demonstrate positive effect of T‐QY305 on the simultaneous inhibition of both cutaneous adverse reaction and diarrhea in animal models. The satisfying results obtained from T‐QY305, lead to further process to the isolation of N‐QY305 from T‐QY305, in order to demonstrate that the potency of T‐QY305 originates from the nanostructure N‐QY305. Compared to T‐QY305, N‐QY305 exhibits higher potency upon reducing adverse reactions. The data represent a promising candidate for reducing cutaneous adverse reaction and diarrhea, meanwhile proposing a new strategy to highlight the presence of nanostructures being the “King” of Chinese medicine formula as the pharmacodynamic basis. Chinese medicine formula T‐QY305 can reduce cutaneous adverse reaction and diarrhea induced by EGFRIs both in human and animals, which corresponds to “Jun”‐“Chen”‐“Zuo”‐“Shi” TCM theory. Meanwhile a new strategy is proposed to highlight the presence of nanostructure N‐QY305 being the “King” of Chinese medicine formula as the pharmacodynamic basis.

Bacterial outer membrane vesicle (OMV) is a kind of spherical lipid bilayer nanostructure naturally secreted by bacteria, which has diverse functions such as intracellular and extracellular communication, horizontal gene transfer, transfer of contents to host cells, and eliciting an immune response in host cells. In this review, several methods including ultracentrifugation and precipitation for isolating OMVs were summarized. The latest progresses of OMVs in biomedical fields, especially in vaccine development, cancer treatment, infection control, and bioimaging and detection were also summarized in this review. We highlighted the importance of genetic engineering for the safe and effective application and in facilitating the rapid development of OMVs. Finally, we discussed the bottleneck problems about OMVs in preparation and application at present and put forward our own suggestions about them. Some perspectives of OMVs in biomedical field were also provided.

The infusion of chimaeric antigen receptor (CAR) T cells can trigger the release of life-threatening supraphysiological levels of pro-inflammatory cytokines. However, uncertainty regarding the timing and severity of such cytokine release syndrome (CRS) demands careful monitoring of the conditions required for the administration of neutralizing antibodies. Here we show that a temperature-sensitive hydrogel conjugated with antibodies for the pro-inflammatory cytokine interleukin-6 (IL-6) and subcutaneously injected before the infusion of CAR-T cells substantially reduces the levels of IL-6 during CRS while maintaining the therapy’s antitumour efficacy. In immunodeficient mice and in mice with transplanted human haematopoietic stem cells, the subcutaneous IL-6-adsorbing hydrogel largely suppressed CAR-T-cell-induced CRS, substantially improving the animals’ survival and alleviating their levels of fever, hypotension and weight loss relative to the administration of free IL-6 antibodies. The implanted hydrogel, which can be easily removed with a syringe following a cooling-induced gel–sol transition, may allow for a shift in the management of CRS, from monitoring to prevention. A subcutaneously injected hydrogel conjugated with antibodies for interleukin-6 substantially reduces the levels of the cytokine during chimaeric antigen receptor T-cell therapy while maintaining its antitumour efficacy.