Smart medicine最新文献

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, down-regulate 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.

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 cell-penetrating 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.

[This corrects the article DOI: 10.1002/SMMD.20220013.].

Change in p53 Nuclear Localization in Response to Extracellular Matrix Stiffness Description: The cover image uses a blue sphere to represent the nucleus and a black area to represent the cytoplasm. We use orange and green to represent the subcellular localisation of p53 in cells after soft and rigid substrate treatment, respectively. It can be seen that the softer substrate significantly increased p53 nuclear localisation in chondrocytes.

Liver tissue engineering offers potential in liver transplantation, while the development of hydrogels for scalable scaffolds incorporating natural components and effective functionalities is ongoing. Here, we propose a novel microfluidic 3D printing hydrogel derived from decellularized fish liver extracellular matrix for liver regeneration. By decellularizing fish liver and combining it with gelatin methacryloyl, the hydrogel scaffold retains essential endogenous growth factors such as collagen and glycosaminoglycans. Additionally, microfluidic-assisted 3D printing technology enables precise modulation of the composition and architecture of hydrogels to fulfill clinical requirements. Benefiting from the natural source of materials, the hydrogels exhibit excellent biocompatibility and cellular proliferation capacity for incorporating induced pluripotent stem cell-derived hepatocytes (iPSC-heps). Furthermore, the macroscopic architecture and biomechanical environment of hydrogels foster optimal functional expression of iPSC-heps. Importantly, post-transplantation, the hydrogels significantly enhance survival rates and liver function in mice with acute liver failure, promoting liver regeneration and repair. These findings suggest that microfluidic 3D printed hydrogels represent promising candidates for liver transplantation and functional recovery.

Phospholipid-based liposomes are among the most successful nanodrug delivery systems in clinical use. However, these conventional liposomes present significant challenges including low drug-loading capacity and issues with drug leakage. Drug-phospholipid conjugates (DPCs) and their assemblies offer a promising strategy for addressing these limitations. In this review, we summarize recent advances in the design, synthesis, and application of DPCs for drug delivery. We begin by discussing the chemical backbone structures and various design strategies such as phosphate head embedding and mono-/bis-embedding in the sn-1/sn-2 positions. Furthermore, we highlight stimulus-responsive designs of DPCs and their applications in treating diseases such as cancer, inflammation, and malaria. Lastly, we explore future directions for DPCs development and their potential applications in drug delivery.

Atherosclerosis (AS) is a major cause of cardiovascular disease. In particular, the unpredictable rupture of vulnerable atherosclerotic plaques (VASPs) can cause serious cardiovascular events such as myocardial infarction, stroke, and even sudden death. Therefore, early evaluation of the vulnerability of atherosclerotic plaques is of great importance. However, clinical imaging techniques are only marginally useful in the presence of severe anatomical structural changes, making it difficult to evaluate plaque vulnerability at an early stage. With the development of molecular imaging and nanotechnology, specific nanoprobes constructed for the pathological features of VASPs have attracted much attention for their ability to visualize VASPs early and noninvasively at the cellular and molecular levels. Here, we outline the pathological features of VASPs, analyze the superiority and limitations of current clinical imaging techniques, introduce the rational design principles of nanoprobes, and systematically summarize the application of nanoprobes to visualize the features of VASPs at the cellular and molecular levels. In addition, we discussed the prospects and urgent challenges in this field, and we believe it will provide new ideas for the early and accurate diagnosis of cardiovascular diseases.

Chondrocytes are commonly applied in regenerative medicine and tissue engineering. Thus, the discovery of optimal culture conditions to obtain cells with good properties and behavior for transplantation is important. In addition to biochemical cues, physical and biomechanical changes can affect the proliferation and protein expression of chondrocytes. Here we investigated the effect of extracellular matrix stiffness on mouse articular chondrocyte phenotype, growth, and subcellular p53 localization. Chondrocytes were seeded on collagen-coated substrates varying in elasticity: 0.5 and 100 kPa. Immunocytochemical staining and immunoblotting showed that a softer substrate significantly increased p53 nuclear localization in chondrocytes. Furthermore, we identified microRNA-532 (miR-532) as a potential p53 target gene to influence cell function, indicating a new target for tissue engineering. These findings provide insight into the influence of physical cues on cell phenotype maintenance and could help improve understanding of cartilage-related pathologies such as osteoarthritis.

Bioorthogonal chemistry, recognized as a highly efficient tool in chemical biology, has shown significant value in cancer treatment. The primary objective is to develop efficient delivery strategies to achieve enhanced bioorthogonal drug treatment for tumors. Here, Janus microparticles (JMs) loaded with cyclooctene-modified doxorubicin prodrug (TCO-DOX) and tetrazine-modified indocyanine green (Tz-ICG) triggers are reported. Besides activating TCO-DOX, Tz-ICG is also a photothermal agent used in photothermal therapy (PTT), enabling the simultaneous use of biorthogonal chemotherapy and PTT. Additionally, the DOX could be significantly reduced in systemic toxicity with the modification of cyclooctene. Thus, the developed drug-carrying JMs system exhibits effective tumor cell killing in vitro and effectively inhibits tumor local progress and distant lung metastasis after postoperative treatment with good safety. These results demonstrate that the prepared JMs provide a paradigm for bioorthogonal prodrug activation and localized delivery, and hold great promise for cancer therapy as well as other related applications.