Tamanna Binte Huq, Sudip Kumar Dam, Doaha Awad, Punnya Anil Kumar Jeeja, Farzana Ferdous, Juan L. Vivero-Escoto
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引用次数: 0
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a 5-year survival rate below 13% and limited treatment options due to rapid metastasis and pronounced chemoresistance. Gemcitabine (Gem) remains a first-line chemotherapy agent; however, its clinical efficacy is hindered by poor cellular uptake, incomplete activation, and acquired drug resistance. To address these limitations, we develop redox-responsive mesoporous silica nanoparticles (MSNs) for the mono- and codelivery of Gem and Cisplatin (cisPt). In this work, we tune the loading and ratio of Gem and cisPt within MSNs. To evaluate the therapeutic potential of MSN-based delivery system in Gem-resistant (GR) PDAC cell lines, we establish murine (GR-KCM) and human (GR-BxPC3) cell models and further evaluate the efficacy in highly GR human cell lines (AsPC1 and HPAFII). In vitro studies demonstrate that Gem-MSNs (10%wt) and Gem-cisPt-MSN (10:9%wt) exhibit the strongest cytotoxicity, even in GR models. Notably, the combination Gem-cisPt-MSN (18:9%wt) induces pronounced S-phase cell cycle arrest, apoptosis, and reactive oxygen species. These findings underscore the potential of MSN-based drug delivery systems to enhance chemotherapy efficacy in treatment-refractory PDAC.
期刊介绍：
Advanced NanoBiomed Research will provide an Open Access home for cutting-edge nanomedicine, bioengineering and biomaterials research aimed at improving human health. The journal will capture a broad spectrum of research from increasingly multi- and interdisciplinary fields of the traditional areas of biomedicine, bioengineering and health-related materials science as well as precision and personalized medicine, drug delivery, and artificial intelligence-driven health science.
The scope of Advanced NanoBiomed Research will cover the following key subject areas:
▪ Nanomedicine and nanotechnology, with applications in drug and gene delivery, diagnostics, theranostics, photothermal and photodynamic therapy and multimodal imaging.
▪ Biomaterials, including hydrogels, 2D materials, biopolymers, composites, biodegradable materials, biohybrids and biomimetics (such as artificial cells, exosomes and extracellular vesicles), as well as all organic and inorganic materials for biomedical applications.
▪ Biointerfaces, such as anti-microbial surfaces and coatings, as well as interfaces for cellular engineering, immunoengineering and 3D cell culture.
▪ Biofabrication including (bio)inks and technologies, towards generation of functional tissues and organs.
▪ Tissue engineering and regenerative medicine, including scaffolds and scaffold-free approaches, for bone, ligament, muscle, skin, neural, cardiac tissue engineering and tissue vascularization.
▪ Devices for healthcare applications, disease modelling and treatment, such as diagnostics, lab-on-a-chip, organs-on-a-chip, bioMEMS, bioelectronics, wearables, actuators, soft robotics, and intelligent drug delivery systems.
with a strong focus on applications of these fields, from bench-to-bedside, for treatment of all diseases and disorders, such as infectious, autoimmune, cardiovascular and metabolic diseases, neurological disorders and cancer; including pharmacology and toxicology studies.
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