Lipid‐based nanoparticles as drug delivery systems for cancer immunotherapy

Abstract

Immune checkpoint inhibitors (ICIs) have shown remarkable success in cancer treatment. However, in cancer patients without sufficient antitumor immunity, numerous data indicate that blocking the negative signals elicited by immune checkpoints is ineffective. Drugs that stimulate immune activation‐related pathways are emerging as another route for improving immunotherapy. In addition, the development of nanotechnology presents a promising platform for tissue and cell type‐specific delivery and improved uptake of immunomodulatory agents, ultimately leading to enhanced cancer immunotherapy and reduced side effects. In this review, we summarize and discuss the latest developments in nanoparticles (NPs) for cancer immuno‐oncology therapy with a focus on lipid‐based NPs (lipid‐NPs), including the characteristics and advantages of various types. Using the agonists targeting stimulation of the interferon genes (STING) transmembrane protein as an exemplar, we review the potential of various lipid‐NPs to augment STING agonist therapy. Furthermore, we present recent findings and underlying mechanisms on how STING pathway activation fosters antitumor immunity and regulates the tumor microenvironment and provide a summary of the distinct STING agonists in preclinical studies and clinical trials. Ultimately, we conduct a critical assessment of the obstacles and future directions in the utilization of lipid‐NPs to enhance cancer immunotherapy.

Enhancing immunotherapy outcomes by targeted remodeling of the tumor microenvironment via combined cGAS-STING pathway strategies

“…The clinical efficacy of STING agonists is constrained by several factors, including inadequate cytoplasmic delivery, swift immune clearance, lack of specific cellular targeting, and systemic inflammatory responses ( 140 ). The progression in STING agonist development has reached a critical impasse, akin to many contemporary immunotherapeutic agents ( 140 ). Consequently, the current studies have pivoted towards the utilization of varied vectors for STING agonist administration ( 140 ).…”

“…The progression in STING agonist development has reached a critical impasse, akin to many contemporary immunotherapeutic agents ( 140 ). Consequently, the current studies have pivoted towards the utilization of varied vectors for STING agonist administration ( 140 ). The advent of nanotechnology offers a promising avenue for targeted delivery to specific tissues and cells, enhancing the absorption of immunomodulatory agents.…”

“…A deep understanding of the dual role of STING pathway activation in halting cancer progression is imperative. Clearer treatment protocols and the identification of selective biomarkers for specific tumor types, which can predict the therapeutic benefits of STING activation, are urgently needed ( 140 ). Benguigui et al.…”

Nanotechnology’s frontier in combatting infectious and inflammatory diseases: prevention and treatment

“…This is also a potential direction for the future development of mRNA vaccines. Notably, LNP-mRNA vaccines have also demonstrated potential in cancer immunotherapy, 692 , 693 prevention or treatment of allergies and autoimmune diseases, 694 – 697 and even gene replacement therapy for rare genetic diseases. 698 It should be highlighted that other nanovaccine platforms have shown significant potential in preventing infectious diseases like SARS-CoV-2.…”

Emerging Targets and Therapeutics in Immuno-Oncology: Insights from Landscape Analysis

“…Lipid NPs – Lipid NPs are currently the most widely used NPs and are exhibiting a higher growth rate as compared to other NPs in the field of cancer immunotherapy (Figure ). Lipid-based NPs are superior to other nanosized drug delivery systems in minimizing systemic toxicity while maintaining adequate solubility and are thus the most common type of regulatory approved nanomedicines .…”