Targeted Therapy of Pancreatic Cancer: Overcoming the challenges by Nanoparticle-Based Drug Delivery Systems

Pancreatic adenocarcinoma (PDAC) remains a formidable challenge due to its aggressive nature and poor prognosis, and is expected to become the second leading cause of cancer-related death by ۲۰۳۰. Despite advancements in treatment, the ۵-year survival rate remains less than ۵%. PDAC poses significant therapeutic challenges due to its dense stroma and resistance to conventional treatments. Nanoparticulate drug delivery systems, including albumin-based nanoparticles, liposomal nanoformulations, and polymeric nanoparticles, offer promising approaches to overcome these limitations by enhancing drug delivery and reducing off-target toxicity, which is common in traditional chemotherapy regimens. Methods: We conducted a thorough literature search using Google Scholar and PubMed to identify relevant articles published between January ۲۰۲۰ and July ۲۰۲۴. Our search was conducted using specific keywords and related MeSH terms, including "targeted therapy", "nanoparticulate systems", "nanoparticle-based drug delivery", "nanoformulations", "polymeric drug delivery", "albumin", "liposomes", "PDAC", and "pancreatic cancer." Additionally, we used the cited works within these articles to further expand our understanding of the field. The review focuses on three primary types of nanoparticles: albumin-based nanoparticles, liposomes, and polymeric nanoparticles. We discuss their unique properties, advantages, and limitations. Furthermore, we delve into strategies for improving drug delivery efficiency, such as surface modification, active targeting, and stimuli-responsive release. Results: Nanoparticle-based drug delivery systems for pancreatic cancer offer improved drug accumulation, efficacy, and reduced side effects over traditional treatments. Albumin-based nanoparticles, known for their enhanced solubility, prolonged circulation time, and reduced toxicity, offer promising pharmacokinetic properties for targeted drug delivery. Examples of widely used albumin-based systems include albumin nanoparticles and albumin-bound liposomes. Approved drugs designed with albumin-based systems for pancreatic cancer include nab-paclitaxel (Abraxane), which is currently used in combination with gemcitabine as a first-line treatment for metastatic pancreatic cancer. Liposomal nanoparticles, characterized by their excellent biocompatibility and ability to encapsulate various drug types, have shown promising results in preclinical and clinical studies for pancreatic cancer, but there are currently no approved liposomal-based drugs specifically for this disease. However, several under-investigation liposomal systems are being explored, including liposomes functionalized with tumor-specific antibodies, liposomes loaded with combination therapies (e.g., chemotherapy and immunotherapy), and liposomes designed to overcome drug resistance. Polymeric nanoparticles, offering versatility in terms of composition and size, allow for controlled drug release and targeted delivery. They can be designed with biodegradable or non-biodegradable properties to suit specific therapeutic needs. Examples of polymeric systems include polymeric micelles, dendrimers, and polymeric nanoparticles. While there are currently no approved polymeric-based systems specifically for pancreatic cancer, several polymers and types are under investigation. Commonly used polymers include poly(lactic-co-glycolic acid) (PLGA), poly(ethylene glycol) (PEG), and chitosan. Investigational polymeric nanoparticles for pancreatic cancer include paclitaxel-loaded PLGA nanoparticles and gemcitabine-loaded chitosan nanoparticles. Conclusion: Nanoparticle-based drug delivery systems hold great potential for improving treatment outcomes in pancreatic cancer. By addressing the challenges associated with traditional therapies, these systems offer a promising avenue for developing more effective and targeted treatments. Future research should focus on optimizing nanoparticle designs, evaluating clinical efficacy, and addressing potential challenges such as biocompatibility and manufacturing scalability.

کلیدواژه ها:

pancreatic cancer ، PDAC ، targeted therapy ، nanomedicine ، nanoparticle-based drug delivery