Mitochondria are crucial to cellular physiology, and growing evidence highlights the significant impact of mitochondrial dysfunction in diabetes, aging, neurodegenerative disorders, and cancers. Therefore, mitochondrial transplantation shows great potential for therapeutic use in treating these diseases. However, transplantation process is notably challenging due to very low efficiency and rapid loss of bioactivity post-isolation, leading to poor reproducibility and reliability. In this study, we develop a novel strategy to form a nanometer-thick protective shell around isolated mitochondria using Metal-Organic Frameworks (MOFs) through biomineralization. Our findings demonstrate that this encapsulation method effectively maintains mitochondria bioactivity for at least 4 weeks at room temperature. Furthermore, the efficiency of intracellular delivery of mitochondria is significantly enhanced through the surface functionalization of MOFs with polyethyleneimine (PEI) and the cellpenetrating peptide Tat. The successful delivery of mitochondria isolated from non-tumorigenic cells into cancer cells results in notable tumor-suppressive effects. Taken together, our technology represents a significant advancement in mitochondria research, particularly on understanding their role in cancer. It also lays the groundwork for utilizing mitochondria as therapeutic agents in cancer treatment.

Glucocorticoids such as dexamethasone have shown promising therapeutic effects in conquering oral ulcers. Challenges in this area are focused on enhancing the localized curative effects and responsive release. Herein, we presented a novel MXene-integrated responsive hydrogel microneedle delivering dexamethasone to promote the healing of oral ulceration. By loading MXene, the hydrogel microneedles enable NIR (Near Infrared)-responsive release of the inner dexamethasone for inflammation control and tissue regeneration. In addition, the MXene-induced local hyperthermia could inhibit the bacteria, preventing the possible infection of ulcer lesions in the oral cavity. Based on these features, we demonstrated that our strategy could relieve local inflammation, promote tissue reconstruction, and accelerate wound healing in rat oral ulcer models. Overall, these NIR-responsive MXene-integrated hydrogel microneedles show significant promise in promoting ulcer healing and bring new ways for oral disease treatment.

Allergic contact dermatitis (ACD) is an inflammatory dermatitis with a high morbidity and recurrence rate. Scientific attention is focused on the development of safe and comfortable therapeutics of ACD. Herein, we propose a natural matrine-integrated pollen delivery system for the ACD treatment. Sunflower pollens were collected and defatted to serve as adhesive drug carriers for matrine. Specifically, the exquisite porous and hollow structures of the pollen shells can absorb matrine and realize the sustained drug release. Besides, the prickly surface morphology can strongly adhere to the inflamed skin sites, which can prolong the duration of the drug. By utilizing them in an ACD model and an acute pruritus model of mice, we have demonstrated that these matrine-integrated pollen shells can decrease the swelling degree of mice ears and weight loss, downregulate inflammatory response, and improve the scratching times. These results indicate that our matrine-integrated pollen delivery systems have great potential to serve as natural topical preparations for skin disease therapy.

Wound healing has been a continuous critical focus in clinical practice, posing the ongoing challenges and burdens to patients. Current attempts tend to develop multi-drug loaded patches with spatial design. Herein, we present a multifunctional microneedle patch that integrates different drugs into separated regions for wound treatment. The microneedle patch is composed of silk fibroin-methacryloyl (SilMA) as the base, loaded with silver nanoparticles (AgNPs) and has gelatin methacryloyl (GelMA) tips loaded with vascular endothelial growth factor (VEGF). The backing is endowed with antimicrobial properties by AgNPs act as an antimicrobial barrier against bacterium invasion. In addition, the tips encapsulated with VEGF can effectively promote cell proliferation and angiogenesis, which is favorable for wound repair. Based on these characteristics, such an integrated microneedle system significantly prevented bacterial infection and promoted wound healing in vivo. Therefore, it is conceived that such a system can find more practical values in wound healing and other fields.