Nanocarriers for pancreatic cancer imaging, treatments, and immunotherapies

Abstract

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.

Multifunctional Lipid Bilayer Nanocarriers for Cancer Immunotherapy in Heterogeneous Tumor Microenvironments, Combining Immunogenic Cell Death Stimuli with Immune Modulatory Drugs

“…The use of laser excitation in combination with multiple-component nanoparticles was shown to significantly prolong survival in Panc02-bearing mice compared with monotherapy or control groups. An extensive review on the use of nanocarriers for pancreatic treatment, immunotherapy, and imaging was recently published by Liu et al 105 C.2. Use of Lipid-Bilayer-Coated Carriers for TNBC Chemo-immunotherapy.…”

The Next Frontier in Pancreatic Cancer: Targeting the Tumor Immune Milieu and Molecular Pathways

“…The establishment of mFOLFIRINOX and GemNab as the standard of care for advanced PDAC likely represented the pinnacle of chemotherapy regimens for this disease. The future of PDAC treatment hinges on (1) better understanding of the TME and the tumor immune milieu to allow more effective immunotherapy approaches to overcome the “cold tumor” properties, (2) further characterization of the various signaling and metabolic pathways in PDAC to help uncover new targets and synergies, and (3) leaning on new technologies in drug development (such as X-ray crystallography) and drug delivery (i.e., with novel nanocarriers) [ 163 ]. It is essential that we improve the prognosis of this notoriously challenging and deadly cancer.…”

Nanoparticle-based immunotherapy of pancreatic cancer

“…These NPs showed an enhanced anti-tumor response triggered by reactivated T cells and complemented by a significant release of inflammatory cytokines such as TNF-α and IFN-γ (Yu et al, 2021). In this regard, using NPs as drug carriers could be an effective approach to increase the efficacy of the ICI therapy for PC and overcome the resistance to conventional cancer therapy (Liu et al, 2022). Despite the optimistic outcome observed by blocking ICs in immunotherapies of metastatic cancer, the effect on metastatic PC has been relatively moderate.…”