Cartilage is solid connective tissue that recovers slowly from injury, and pain and dysfunction from cartilage damage affect many people. The treatment of cartilage injury is clinically challenging and there is no optimal solution, which is a hot research topic at present. With the rapid development of 3D printing technology in recent years, 3D bioprinting can better mimic the complex microstructure of cartilage tissue and thus enabling the anatomy and functional regeneration of damaged cartilage. This article reviews the methods of 3D printing used to mimic cartilage structures, the selection of cells and biological factors, and the development of bioinks and advances in scaffold structures, with an emphasis on how 3D printing structure provides bioactive cargos in each stage to enhance the effect. Finally, clinical applications and future development of simulated cartilage printing are introduced, which are expected to provide new insights into this field and guide other researchers who are engaged in cartilage repair.

Hyperbranched polymers (HBPs) have drawn great interest in the biomedical field on account of their special morphology, low viscosity, self-regulation, and facile preparation methods. Moreover, their large intramolecular cavities, high biocompatibility, biodegradability, and targeting properties render them very suitable for anti-tumor drug delivery. Recently, exploiting the specific characteristics of the tumor microenvironment, a range of multifunctional HBPs responsive to the tumor microenvironment have emerged. By further introducing various types of drugs through physical embedding or chemical coupling, the resulting HBPs based delivery systems have played a crucial part in improving drug stability, increasing effective drug concentration, decreasing drug toxicity and side effects, and enhancing anti-tumor effect. Here, based on different types of tumor microenvironment stimulation signals such as pH, redox, temperature, etc., we systematically review the preparation and response mechanism of HBPs, summarize the latest advances in drug delivery applications, and analyze the challenges and future research directions for such nanomaterials in biomedical clinical applications.

Extracellular vesicles (EVs) are a part of a cell-to-cell communication system of prokaryotic and eukaryotic organisms. Their ability to penetrate biological barriers and to transfer molecules between cells shows their potential as a novel class of drug delivery platform. However, because of the great heterogeneity of EVs and the complexity of biological matrices from which they are typically isolated, reliable quality control procedures need to be established to ensure their safety for medical use. According to current recommendations, quantification of EVs, confirmation of their identity, and purity assessment require the use of several analytical techniques, including particle-size distribution analysis, proteomics, and electron microscopy, making the characterization process demanding. Capillary electrophoresis (CE) has recently emerged as an alternative tool for EV characterization. In this study, the available literature on this novel concept for EV characterization was reviewed. Its performance was critically evaluated and compared with currently used methods. The utility of CE in the quality control of EV-based medicines was discussed.

Tumor treatment remains a significant medical challenge, with many traditional therapies causing notable side effects. Recent research has led to the development of immunotherapy, which offers numerous advantages. Bacteria inherently possess motility, allowing them to preferentially colonize tumors and modulate the tumor immune microenvironment, thus influencing the efficacy of immunotherapy. Bacterial outer membrane vesicles (OMVs) secreted by gram-negative bacteria are nanoscale lipid bilayer structures rich in bacterial antigens, pathogen-associated molecular patterns (PAMPs), various proteins, and vesicle structures. These features allow OMVs to stimulate immune system activation, generate immune responses, and serve as efficient drug delivery vehicles. This dual capability enhances the effectiveness of immunotherapy combined with chemotherapy or phototherapy, thereby improving anticancer drug efficacy. Current research has concentrated on engineering OMVs to enhance production yield, minimize cytotoxicity, and improve the safety and efficacy of treatments. Consequently, OMVs hold great promise for applications in tumor immunotherapy, tumor vaccine development, and drug delivery. This article provides an overview of the structural composition and immune mechanisms of OMVs, details various OMVs modification strategies, and reviews the progress in using OMVs for tumor treatment and their anti-tumor mechanisms. Additionally, it discusses the challenges faced in translating OMV-based anti-tumor therapies into clinical practice, aiming to provide a comprehensive understanding of OMVs' potential for in-depth research and clinical application.

A wide number of natural molecules demonstrated neuroprotective effects on synaptic plasticity defects induced by amyloid-β (Aβ) in ex vivo and in vivo Alzheimer's disease (AD) models, suggesting a possible use in the treatment of this neurodegenerative disorder. However, several compounds, administered parenterally and orally, are unable to reach the brain due to the presence of the blood-brain barrier (BBB) which prevents the passage of external substances, such as proteins, peptides, or phytocompounds, representing a limit to the development of treatment for neurodegenerative diseases, such as AD. The combination of nano vesicular systems, as colloidal systems, and nose to brain (NtB) delivery depicts a new nanotechnological strategy to overtake this limit and to develop new treatment approaches for brain diseases, including the use of natural molecules in combination therapy for AD. Herein, we will provide an updated overview, examining the literature of the last 20 years and using specific keywords that provide evidence on natural products with the ability to restore synaptic plasticity alterations in AD models, and the possible application using safe and non-invasive strategies focusing on nano vesicular systems for NtB delivery.

Gynecological cancers present significant treatment challenges due to drug resistance and adverse side effects. This review explores advancements in lysosomal escape mechanisms, essential for enhancing nano-therapeutic efficacy. Strategies such as pH-sensitive linkers and membrane fusion are examined, showcasing their potential to improve therapeutic outcomes in ovarian, cervical, and uterine cancers. We delve into novel materials and strategies developed to bypass the lysosomal barrier, including pH-sensitive linkers, fusogenic lipids, and nanoparticles (NPs) engineered for endosomal disruption. Mechanisms such as the proton sponge effect, where NPs induce osmotic swelling and rupture of the lysosomal membrane, and membrane fusion, which facilitates the release of therapeutic agents directly into the cytoplasm, are explored in detail. These innovations not only promise to improve therapeutic outcomes but also minimize side effects, marking a significant step forward in the treatment of ovarian, cervical, and uterine cancers. By providing a comprehensive analysis of current advancements and their implications for clinical applications, this review sheds light on the potential of lysosomal escape strategies to revolutionize gynecological cancer treatment, setting the stage for future research and development in this vital area.

Urinary system tumors include malignancies of the bladder, kidney, and prostate, and present considerable challenges in diagnosis and treatment. The conventional therapeutic approaches against urinary tumors are limited by the lack of targeted drug delivery and significant adverse effects, thereby necessitating novel solutions. Intelligent nanomedicine has emerged as a promising therapeutic alternative for cancer in recent years, and uses nanoscale materials to overcome the inherent biological barriers of tumors, and enhance diagnostic and therapeutic accuracy. In this review, we have explored the recent advances and applications of intelligent nanomedicine for the diagnosis, imaging, and treatment of urinary tumors. The principles of nanomedicine design pertaining to drug encapsulation, targeting and controlled release have been discussed, with emphasis on the strategies for overcoming renal clearance and tumor heterogeneity. Furthermore, the therapeutic applications of intelligent nanomedicine, its advantages over traditional chemotherapy, and the challenges currently facing clinical translation of nanomedicine, such as safety, regulation and scalability, have also been reviewed. Finally, we have assessed the potential of intelligent nanomedicine in the management of urinary system tumors, emphasizing emerging trends such as personalized nanomedicine and combination therapies. This comprehensive review underscores the substantial contributions of nanomedicine to the field of oncology and offers a promising outlook for more effective and precise treatment strategies for urinary system tumors.

A series of biodegradable nanoparticle-based drug delivery systems have been designed utilizing poly(β-amino ester)-guanidine-phenylboronic acid (PBAE-G) polymers. In this study, a novel Lentinan-Functionalized PBAE-G-nanodiamond system was developed to carry ovalbumin (LNT-PBAE-G-ND@OVA). The impact of this drug delivery system on the activation and maturation of macrophages was then assessed. Furthermore, LNT-PBAE-G-ND@OVA induced potent antibody response and showed no obvious toxicity in vitro and in vivo. Moreover, treatment with LNT-PBAE-G-ND@OVA was sufficient to alter the expression of genes associated with the cGAS-STING pathway, and the LNT-PBAE-G-ND@OVA induced upregulation of costimulatory molecules. LNT-PBAE-G-ND@OVA treatment was sufficient to induce macrophage activation through a complex mechanism in which cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) signaling plays an integral role.

Radiotherapy (RT) is one of the most common treatments for cancer. However, intracellular glutathione (GSH) plays a key role in protecting cancer from radiation damage. Herein, we have developed a platelet membrane biomimetic nanomedicine (PMD) that induces double GSH consumption to enhance tumor radioimmunotherapy. This biomimetic nanomedicine consists of an external platelet membrane and internal organic mesoporous silica nanoparticles (MON) loaded with 2-deoxy-D-glucose (2-DG). Thanks to the tumor-targeting ability of the platelet membranes, PMD can target and aggregate to the tumor site, which is internalized by tumor cells. Within tumor cells overexpressing GSH, MON reacts with GSH to degrade and release 2-DG. This step initially depletes the intracellular GSH content. The subsequent release of 2-DG inhibits glycolysis and adenosine triphosphate (ATP) production, ultimately leading to secondary GSH consumption. This nanodrug combines dual GSH depletion, starvation therapy, and RT to promote immunogenic cell death and stimulate the systemic immune response. In the bilateral tumor model in vivo, distal tumor growth was also well suppressed. The proportion of mature dendritic cells (DC) and CD8⁺ T cells in the mice was increased. This indicates that PMD can promote anti-tumor radioimmunotherapy and has good prospects for clinical application.

In our prior research, polymer nanoparticles (NPs) containing tobramycin displayed robust antibacterial efficacy against biofilm-embedded Pseudomonas aeruginosa (P. aeruginosa) and Burkholderia cenocepacia (B. cenocepacia) cells, critical pathogens in cystic fibrosis. In the current study, we investigated the deposition of a nanoparticulate carrier composed of poly(d,l-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol)-block-PLGA (PEG-PLGA) that was either covalently bonded with cyanine-5-amine (Cy5) or noncovalently bound with freely embedded cationic rhodamine B (RhB), which served as a drug surrogate. After exposing these NPs to bacteria, we performed cell fractionation and fluorescence analysis, which highlighted the accumulation of Cy5 in the outer membranes (OMs) and the accumulation of RhB in the cytoplasm (CP) of cells. The results indicated that these organic NPs are effective vehicles for targeted antibiotic delivery in bacterial cells, explaining the observed increase in the efficacy of encapsulated tobramycin against biofilms. This work emphasizes the potential of PEG-PLGA-based formulations for advanced drug delivery strategies.

Particle size and surface properties are crucial for lymphatic drainage (LN), dendritic cell (DC) uptake, DC maturation, and antigen cross-presentation induced by nanovaccine injection, which lead to an effective cell-mediated immune response. However, the manner in which the particle size and surface properties of vaccine carriers such as mesoporous silica nanoparticles (MSNs) affect this immune response is unknown. We prepared 50, 100, and 200 nm of MSNs that adsorbed ovalbumin antigen (OVA) while modifying β-glucan to enhance immunogenicity. The results revealed that these MSNs with different particle sizes were just as efficient in vitro, and MSNs with β-glucan modification demonstrated higher efficacy. However, the in vivo results indicated that MSNs with smaller particle sizes have stronger lymphatic targeting efficiency and a greater ability to promote the maturation of DCs. The results also indicate that β-glucan-modified MSN, with a particle size of ∼100 nm, has a great potential as a vaccine delivery vehicle and immune adjuvant and offers a novel approach for the delivery of multiple therapeutic agents that target other lymph-mediated diseases.

Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost, sustainability, and tissue targeting. Thus, they hold promise for disease treatment and drug delivery. In this study, we proposed a time-efficient method, PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles (GDNVs). Subsequently, curcumin (CUR) was loaded onto GDNV by ultrasonic incubation. The optimum conditions for ginger-derived nanovesicles loaded with curcumin (CG) were ultrasound time of 3 min, a carrier-to-drug ratio (GDNV:CUR) of 1:1. The study achieved a high loading capacity (94.027% ± 0.094%) and encapsulation efficiency (89.300% ± 0.344%). Finally, the drugs' in vivo distribution and anti-colitis activity were investigated in mice. CG was primarily distributed in the colon after oral administration. Compared to CUR and GDNV, CG was superior in improving disease activity, colon length, liver and spleen coefficients, myeloperoxidase activity, and biochemical factor levels in ulcerative colitis (UC) mice. In addition, CG plays a protective role against UC by modulating serum metabolite levels and gut flora. In summary, our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

The aim of the research is to increase the applicability of lipopeptides as drugs. To this end, non-ionic triblock copolymers, namely poloxamers, were applied. The physico-chemical properties of poloxamers vary depending on the length of the blocks. In our study, we experimented with different types and systematically investigated the variation of the critical micelle concentration (CMC) of poloxamers at 25 and 37 °C in different media. In addition, the cytotoxicity of the different poloxamer micelles on three different cell lines was evaluated, and based on the results, Plur104, Plur123, and Plur127 were selected. Fatty acid elongated derivatives of a short antibacterial peptide (pL1), a medium-sized anticancer peptide (pCM15), and a branched-chain vaccine antigen (pATIPC) were used as lipopeptide models, and their formulations with the selected poloxamers were investigated. The solubility and homogeneity of the lipopeptides were significantly increased, and dynamic light scattering (DLS) measurements showed the formation of small particles of around 20 nm, which were well reproducible and storable. Similar homogenous micelle formation was observed after freeze-drying and reconstitution with water. The pL1 lipopeptide, formulated with the selected poloxamers, exhibited enhanced antibacterial activity with significantly reduced haemolytic side effects. The pCM15 peptide, when incorporated into poloxamer micelles, showed significantly enhanced cytotoxicity against tumor cells. Additionally, the internalization rate of poloxamer-formulated pATIPC peptide by antigen-presenting model cells exceeded that of the unformulated peptide. Our results demonstrate the potential of poloxamers as promising tools for the formulation of lipopeptides and for the optimization of their selectivity.

Diabetes mellitus (DM) is a major metabolic disease endangering global health, with diabetic nephropathy (DN) as a primary complication lacking curative therapy. Sporoderm-broken spores of Ganoderma lucidum (GLP), an herbal medicine, has been used for the treatment of metabolic disorders. In this study, DN was induced in Sprague-Dawley rats using streptozotocin (STZ) and a high-fat diet (HFD), and the protective mechanisms of GLP were investigated through transcriptomic, metabolomic, and network pharmacology (NP) analyses. Our results demonstrated that GLP intervention ameliorated renal damage and inflammation levels in DN rats. Integrative metabolomic and transcriptomic analysis revealed that GLP treatment modulated glucose and cellular energy metabolisms by regulating relevant genes. GLP significantly suppressed the inflammations by impacting glucose and energy metabolism-related gene expression (Igfbp1 and Angptl4) and enhanced metabolic biomarkers of 4-Aminocatechol. In addition, NP analysis further indicated that GLP may efficiently alleviate DN via immune-related pathways. In conclusion, this study provides supportive evidence of the anti-inflammatory effects of GLP supplements, highlighting their potential for promising clinical applications in treating DN.

Reactive oxygen species (ROS)-mediated anticancer modalities, which disturb the redox balance of cancer cells through multi-pathway simulations, hold great promise for effective cancer management. Among these, cooperative physical and biochemical activation strategies have attracted increasing attention because of their spatiotemporal controllability, low toxicity, and high therapeutic efficacy. Herein, we demonstrate a nanogel complex as a multilevel ROS-producing system by integrating chloroperoxidase (CPO) into gold nanorod (AuNR)-based nanogels (ANGs) for cascade-amplifying photothermal-enzymatic synergistic tumor therapy. Benefiting from photothermal-induced hyperthermia upon near-infrared (NIR) laser exposure, the exogenous ROS (including H₂O₂) were boosted by the AuNR nanogel owing to the intercellular stress response. This ultimately promoted the efficient enzyme-catalyzed reaction of loaded CPO combined with the rich endogenous H₂O₂ in tumor cells to significantly elevate intracellular ROS levels above the threshold for improved therapeutic outcomes. Both in vitro and in vivo studies have verified the cascade-amplifying ROS-mediated antitumor effects, providing feasible multimodal synergistic tactics for tumor treatment.