Introduction: Cancer of the bladder is one of the most common and life-threatening. Compared with traditional delivery methods, intravesical administration reduces the amount of drugs required, increases the amount of drugs reaching the lesion site, and minimizes systemic exposure to therapeutic agents. To overcome the limitations of urinary voiding, low urothelium permeability, and intermittent catheterization for large dilution and irrigation of drugs in the bladder, magnetic and photothermal-responsive folate receptor-targeted thermal liposomes (FA-TMLs) were designed for the targeted delivery of doxorubicin (DOX) to bladder cancer cells. Methods: Through a microfluidic mixer chip, the magnetic nanoparticles (MNPs), gold nanorods (GNRs) and DOX were encapsulated in folate-modified thermosensitive liposomes to form [email protected] DLS, TEM, DSC, and magnetic hysteresis loop were used to characterize the construction of [email protected]DOX. Results: [email protected] had a size of about 230 nm and exhibited superparamagnetic properties with the saturation magnetization of 20 emu/g. The DOX loading capacity was as high as 0.57 mg/mL. Additionally, drug release of the [email protected] could be controlled by temperature change through the photothermal effect. A 980 nm laser beam was selectively irradiated on the [email protected] to trigger the structural changes of the FA-TMLs, and an average of 95% of the drug was released after 3 hours. The results of cell uptake experiments reveal indicated that [email protected] were able to specifically bind folate-receptor-positive cells and exhibited toxicity to bladder tumor cells. Conclusion: The present results suggest [email protected] have a promising multifunctional response and can act as an ideal multifunctional drug delivery system (DDS) for the treatment of bladder tumors.

Microplastics (MPs) are defined as plastic particles smaller than 5 mm in size, and nanoplastics (NPs) are those MPs with a particle size of less than 1000 nm or 100 nm. The prevalence of MPs in the environment and human tissues has raised concerns about their potential negative effects on human health. Macrophages are the major defence against foreign substances in the intestine, and can be polarized into two types: the M1 phenotype and the M2 phenotype. However, the effect of NPs on the polarization of macrophages remains unclear. Herein, we selected polystyrene, one of the most plastics in the environment and controlled the particle sizes at 50 nm and 500 nm respectively to study the effects on the polarization of macrophages. We used mouse RAW264.7 cell line models in this macrophage-associated study. Experiments on cell absorption showed that macrophages could quickly ingest polystyrene nanoplastics of both diameters with time-dependent uptake. Compared to the untreated group and 10 μg/mL treatment group, macrophages exposed to 50 μg/mL groups (50 nm and 500 nm) had considerably higher levels of CD86, iNOS, and TNF-α, but decreased levels of aCD206, IL-10, and Arg-1. According to these findings, macrophage M1 and M2 polarization can both be induced and inhibited by 50 μg/mL 50 nm and 500 nm polystyrene nanoplastics. This work provided the first evidence of a possible MPs mode of action with appropriate concentration and size through the production of polarized M1, providing dietary and environmental recommendations for people, particularly those with autoimmune and autoinflammatory illnesses.

As a class of short non-coding ribonucleic acids (RNAs), microRNAs (miRNA) regulate gene expression in human cells and are expected to be nucleic acid drugs to regulate and treat a variety of biological processes and diseases. However, the issues with potential materials toxicity, quantity production, poor cellular uptake, and endosomal entrapment limit their further applications in clinical practice. Herein, ZIF-8, a metal-organic framework with noncytotoxic zinc (II) as the metal coordination center, was selected as miRNA delivery vector was used to prepare miR-200c-3p@ZIF-8 in one step by Y-shape microfluidic chip to achieve intracellular release with low toxicity, batch size, and efficient cellular uptake. The obtained miR-200c-3p@ZIF-8 was identified by TEM, particle size analysis, XRD, XPS, and zeta potential. Compared with the traditional hydrothermal method, the encapsulation efficiency of miR-200c-3p@ZIF-8 prepared by the microfluidic method is higher, and the particle size is more uniform and controllable. The experimental results in cellular level verified that the ZIF-8 vectors with low cytotoxicity and high miRNAs loading efficiency could significantly improve cellular uptake and endosomal escape of miRNAs, providing a robust and general strategy for nucleic acid drug delivery. As a model, the prepared miR-200c-3p@ZIF-8 is confirmed to be effective in osteoarthritis treatment.

Introduction: Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degeneration. Chondrocyte inflammation, apoptosis, and extracellular matrix degradation accelerated OA progression. MicroRNA (miRNA) has the potential to be a therapeutic method for osteoarthritis. However, it is difficult to penetrate the cell to exercise its biological function, and its extracellular effect is unclear. Methods: lipo-AgPEI-miR-200c-3p was created by combining miR-200c-3p with silver nitrate polyvinylimine nanoparticles on a microfluidic device. The drug release curve, stability, temperature sensitivity, cytotoxicity, and the impact of lipo-AgPEI-miR-200c-3p on the expression of proteins linked to matrix disintegration, apoptosis, and inflammatory factors were all detected. Results: Results showed that the particle size of Lipo-AgPEI-miR-200c-3p was about 130 nm, the Zeta potential was lowered to 1.08± 0.12 mV. Lipo-AgPEI-miR-200c-3p could increase cell viability, prevent cell apoptosis, and decrease the expression levels of TNF-α, IL-6, IL-1β, and MCP-1 in ADTC5 cells following LPS stimulation. MMP3, MMP13, and ADAMTS-4 expression was downregulated whereas collagen II expression was upregulated. The ZEB2 expression was greatly elevated following LPS stimulation and dramatically decreased following transfection of miR-200c-3p. Collagen II expression rose following transfection of si-ZEB2, whereas the expression levels of inflammatory factors, apoptosis-related proteins, MMP3, MMP13, and ADAMTS-4 decreased. The dual luciferase experiment demonstrated that ZEB2 was the target gene of miR-200c-3p. Conclusion: The synergistic effect of AgPEI and miR-200c-3p can inhibit the inflammatory response, apoptosis, and matrix degradation of chondrocytes. Lipo-AgPEI-miR-200c-3p can also improve transfection efficiency and obtain good physicochemical properties of drugs. miR-200c-3p may be crucial in the development of OA and can influence the target gene ZEB2, control the inflammatory response, apoptosis, and chondrocyte matrix breakdown.

Bone infection is a disease that seriously affects patients’ quality of life and physical health. Traditional treatment methods have many drawbacks. Hydrogels loaded with Traditional Chinese Medicine (TCM), as an emerging treatment strategy, combine the advantages of good biocompatibility of hydrogels, adjustable drug release performance, and multi-target synergistic treatment of TCM, showing great application potential. This article elaborates in detail on the research progress of hydrogels loaded with TCM for the treatment of bone infections, including the classification and characteristics of hydrogels, the mechanism of action of TCM in the treatment of bone infections, the preparation methods of hydrogels loaded with TCM, application examples, advantages, and the challenges and prospects faced. The aim is to provide new ideas and references for the clinical treatment of bone infections.

Response to Letter in regards to Response to Article “Microfluidic Synthesis of miR-200c-3p Lipid Nanoparticles: Targeting ZEB2 to Alleviate Chondrocyte Damage in Osteoarthritis” [Letter]