Pancreatic tumors are highly desmoplastic and immunosuppressive. Delivery and distribution of drugs within pancreatic tumors are compromised due to intrinsic physical and biochemical stresses that lead to increased interstitial fluid pressure, vascular compression, and hypoxia. Immunotherapy-based approaches, including therapeutic vaccines, immune checkpoint inhibition, CAR-T cell therapy, and adoptive T cell therapies, are challenged by an immunosuppressive tumor microenvironment. Together, extensive fibrosis and immunosuppression present major challenges to developing treatments for pancreatic cancer. In this context, nanoparticles have been extensively studied as delivery platforms and adjuvants for cancer and other disease therapies. Recent advances in nanotechnology have led to the development of multiple nanocarrier-based formulations that not only improve drug delivery but also enhance immunotherapy-based approaches for pancreatic cancer. This review discusses and critically analyzes the novel nanoscale strategies that have been used for drug delivery and immunomodulation to improve treatment efficacy, including newly emerging immunotherapy-based approaches. This review also presents important perspectives on future research directions that will guide the rational design of novel and robust nanoscale platforms to treat pancreatic tumors, particularly with respect to targeted therapies and immunotherapies. These insights will inform the next generation of clinical treatments to help patients manage this debilitating disease and enhance survival rates.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality, poor prognosis, and palliative treatments, due to the rapid upregulation of alternative compensatory pathways and desmoplastic reaction. miRNAs, small non-coding RNAs, have been recently identified as key players regulating cancer pathogenesis. Dysregulated miRNAs are associated with molecular pathways involved in tumor development, metastasis, and chemoresistance in PDAC, as well as other cancers. Targeted treatment strategies that alter miRNA levels in cancers have promising potential as therapeutic interventions. miRNA-345 (miR-345) plays a critical role in tumor suppression and is differentially expressed in various cancers, including pancreatic cancer (PC). The underlying mechanism(s) and delivery strategies of miR-345 have been investigated by us previously. Here, we summarize the potential therapeutic roles of miR-345 in different cancers, with emphasis on PDAC, for miRNA drug discovery, development, status, and implications. Further, we focus on miRNA nanodelivery system(s), based on different materials and nanoformulations, specifically for the delivery of miR-345.
This study presents a scoping review of the use of digital health technologies and artificial intelligence (AI) to screen and mitigate risks and mental health consequences associated with adverse childhood experiences (ACEs) among children and youth. A total of 18 search articles were reviewed thoroughly within four main domains: post-traumatic stress disorder (PTSD), suicidal behavior/ideation, anxiety/depression, and attention deficit hyperactivity disorder (ADHD). Findings from the search suggest that the incorporation of digital health technologies stands to improve the quality of related care provisions for the management of mental health consequences of adverse or traumatic events in childhood including PTSD (5%), suicidal behavior/ideation (22%), anxiety/depression (16%), and ADHD (16%). The use of digital health technologies, machine learning tools, natural learning processing, and AI has a positive and encouraging response in mitigating the risks of ACEs. Under proper legal regulations, security, privacy, and confidentiality assurances, digital technologies could assist in mitigating the effects of ACEs and promoting positive childhood experiences (PCEs) in children and young adults, bolstering resilience, and providing reliable public health resources to serve populations in need.
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