Antibiotic resistance is a growing public health threat that complicates the treatment of infections. β-Lactamase enzymes, which hydrolyze the β-lactam ring present in many common antibiotics, are a major cause of this resistance and are produced by a broad range of bacterial pathogens. Here, we developed hydrogels that degrade specifically in the presence of β-lactamases and β-lactamase-producing bacteria as a platform for bacteria-triggered drug delivery. A maleimide-functionalized β-lactamase-cleavable cephalosporin was used as a crosslinker in the fabrication of hydrogels through end-crosslinked polymerization with multiarm thiol-terminated poly(ethylene glycol) macromers via Michael-type addition. We demonstrated that only hydrogels containing the responsive crosslinker were degraded by β-lactamases and β-lactamase-producing bacteria and in an porcine skin infection model. Fluorescent polystyrene nanoparticles, encapsulated in the hydrogels as model cargo, were released at rates that closely tracked hydrogel wet mass loss, confirming β-lactamase-triggered controlled cargo release. Nonresponsive hydrogels, lacking the β-lactam crosslinker, remained stable in the presence of β-lactamases and β-lactamase-producing bacteria and exhibited no change in mass or nanoparticle release. Furthermore, the responsive hydrogels remained stable in non-β-lactamase enzymes, including collagenases and lipases. These hydrogels have the potential to be used as a bacteria-triggered drug delivery system to control unnecessary exposure to encapsulated antimicrobials, which can provide effective infection treatment without exacerbating resistance.
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http://dx.doi.org/10.1021/acsami.2c02614 | DOI Listing |
Adv Sci (Weinh)
January 2025
Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, 710038, P. R. China.
Leaky and structurally abnormal blood vessels and increased pressure in the tumor interstitium reduce the infiltration of CAR-T cells in solid tumors, including triple-negative breast cancer (TNBC). Furthermore, high burden of tumor cells may cause reduction of infiltrating CAR-T cells and their functional exhaustion. In this study, various effector-to-target (E:T) ratio experiments are established to model the treatment using CAR-T cells in leukemia (high E:T ratio) and solid tumor (low E:T ratio).
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January 2025
Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Department of Orthopedic Surgery, Hangzhou Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, 310000, China.
Osteoarthritis (OA) is a globally prevalent degenerative joint disease. Recent studies highlight the role of ferroptosis in OA progression. Targeting ferroptosis regulation presents a promising therapeutic strategy for OA; however, current research primarily focuses on single targets associated with ferroptosis.
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January 2025
The Department of Head and Neck Surgery, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, P. R. China.
Graves' disease (GD) is an autoimmune disorder with a high incidence rate, particularly affecting women of reproductive age. Current treatment modalities for GD carry significant disadvantages, especially for pregnant or nursing women. As a novel extracorporeal therapeutic technique, high-intensity focused ultrasound (HIFU) shows great promise for treating GD; however, its low treatment efficacy impedes clinical application.
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January 2025
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
Precise and effective management of myocardial ischemia/reperfusion injury (MIRI) is still a formidable challenge in clinical practice. Additionally, real-time monitoring of drug aggregation in the MIRI region remains an open question. Herein, a drug delivery system, hesperadin and ICG assembled in PLGA-Se-Se-PEG-IMTP (HI@PSeP-IMTP), is designed to deliver hesperadin and ICG to the MIRI region for in vivo optical imaging tracking and to ameliorate MIRI.
View Article and Find Full Text PDFAdv Healthc Mater
January 2025
Nitte (Deemed to be University), Department of Bio & Nano Technology, Nitte University Centre for Science Education and Research, Mangalore, Karnataka, 575018, India.
Therapeutic strategy for efficiently targeting cancer cells needs an in-depth understanding of the cellular and molecular interplay in the tumor microenvironment (TME). TME comprises heterogeneous cells clustered together to translate tumor initiation, migration, and proliferation. The TME mainly comprises proliferating tumor cells, stromal cells, blood vessels, lymphatic vessels, cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), and cancer stem cells (CSC).
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