Multifunctional nanomedicines with active targeting and stimuli-responsive drug release function utilizing pathophysiological features of the disease are regarded as an effective strategy for treatment of rheumatoid arthritis (RA). Under the inflammatory environment of RA, activated macrophages revealed increased expression of folate receptor and elevated intracellular reactive oxygen species (ROS) level. In this study, we successfully conjugated folate to polyethylene glycol 100 monostearate as film-forming material and further prepared methotrexate (MTX) and catalase (CAT) co-encapsulated liposomes, herein, shortened to FOL-MTX&CAT-L, that could actively target to activated macrophages. Thereafter, elevated intracellular hydrogen peroxide, the main source of ROS, diffused into liposomes and encapsulated CAT catalyzed the decomposition of hydrogen peroxide into oxygen and water. Continuous oxygen-generation inside liposomes would eventually disorganize its structure and release the encapsulated MTX. We characterized the in vitro drug release, cellular uptake and cytotoxicity studies as well as in vivo pharmacokinetics, biodistribution, therapeutic efficacy and safety studies of FOL-MTX&CAT-L. In vitro results revealed that FOL-MTX&CAT-L possessed sufficient ROS-sensitive drug release, displayed an improved cellular uptake through folate-mediated endocytosis and exhibited a higher cytotoxic effect on activated RAW264.7 cells. Moreover, in vivo results showed prolonged blood circulation time of PEGylated liposomes, enhanced accumulation of MTX in inflamed joints of collagen-induced arthritis (CIA) mice, reinforced therapeutic efficacy and minimal toxicity toward major organs. These results imply that FOL-MTX&CAT-L may be used as an effective nanomedicine system for RA treatment.
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http://dx.doi.org/10.3390/pharmaceutics11110582 | DOI Listing |
J Nanobiotechnology
January 2025
Department of Pharmacy The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
Glioblastoma multiforme (GBM) is characterized by pronounced immune escape and resistance to chemotherapy-induced apoptosis. Preliminary investigations revealed a marked overexpression of gasdermin E (GSDME) in GBM. Notably, cisplatin (CDDP) demonstrated a capacity of inducing pyroptosis by activating caspase-3 to cleave GSDME, coupled with the release of proinflammatory factors, indicating the potential as a viable approach of inducing anti-tumor immune activation.
View Article and Find Full Text PDFNat Chem Biol
January 2025
Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Chromatin and transcription regulators are critical to defining cell identity through shaping epigenetic and transcriptional landscapes, with their misregulation being closely linked to oncogenesis. Pharmacologically targeting these regulators, particularly the transcription-activating BET proteins, has emerged as a promising approach in cancer therapy, yet intrinsic or acquired resistance frequently occurs, with poorly understood mechanisms. Here, using genome-wide CRISPR screens, we find that BET inhibitor efficacy in mediating transcriptional silencing and growth inhibition depends on the auxiliary/arm/tail module of the Integrator-PP2A complex (INTAC), a global regulator of RNA polymerase II pause-release dynamics.
View Article and Find Full Text PDFThis article provides an overview of treatment approaches for chronic kidney disease (CKD) in patients with IgA nephropathy (IgAN). IgAN is the most common primary glomerulonephritis and results from an autoimmune reaction to aberrantly glycosylated immunoglobulin A (IgA) antibodies. Although historically considered largely benign, it is now recognized that a significant percentage of patients develop dialysis-dependent kidney disease over the years.
View Article and Find Full Text PDFJ Control Release
January 2025
Department of Orthopedics, Sichuan Provincial People's Hospital, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu 610072, Sichuan, PR China; Chongqing Engineering Laboratory of Nano/Micro Biomedical Detection Technology, Chongqing University of Science and Technology, Chongqing 401331, PR China; Department of Urology, Deyang People's Hospital, Deyang 618099, Sichuan, PR China. Electronic address:
Developing effective nanoplatforms for chemo-immunotherapy to achieve enhanced tumor suppression and systemic antitumor immunity has recently received extensive attention. Herein, we formulated a multifunctional DNA sandwich nanodevice, DSWAC/siPD-L1, based on triangular DNA origami, to implement enhanced cancer chemo-immunotherapy. Taking advantage of the tumor-targeting ability of the AS1411 aptamer, DSWAC/siPD-L1 efficiently delivered doxorubicin (DOX), CpG, and siPD-L1 into tumor cells.
View Article and Find Full Text PDFEur J Pharm Biopharm
January 2025
Department of Chemistry, State University of Londrina, Londrina, PR, Brazil; Department of Pharmaceutical Sciences, State University of Londrina, Londrina, PR, Brazil. Electronic address:
This study aimed to develop patches containing quercetin-loaded microcapsules and to evaluate their in vitro and in vivo safety and efficacy in preclinical surveys. A set of in vitro experiments evidenced the virucidal activity of quercetin against the HSV-1-KOS (sensitive to acyclovir) and HSV-1-AR (resistant to acyclovir) strains, with improved outcomes upon the first. The patches presented a homogeneous aspect, were easily handled, had a suitable bioadhesion, and possessed mechanical properties of soft and weak material, besides a pH compatible with human skin.
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