Emerging Strategies for Immunotherapy of Solid Tumors Using Lipid-Based Nanoparticles

The application of lipid-based nanoparticles for COVID-19 vaccines and transthyretin-mediated amyloidosis treatment have highlighted their potential for translation to cancer therapy. However, their use in delivering drugs to solid tumors is limited by ineffective targeting, heterogeneous organ distribution, systemic inflammatory responses, and insufficient drug accumulation at the tumor. Instead, the use of lipid-based nanoparticles to remotely activate immune system responses is an emerging effective strategy. Despite this approach showing potential for treating hematological cancers, its application to treat solid tumors is hampered by the selection of eligible targets, tumor heterogeneity, and ineffective penetration of activated T cells within the tumor. Notwithstanding, the use of lipid-based nanoparticles for immunotherapy is projected to revolutionize cancer therapy, with the ultimate goal of rendering cancer a chronic disease. However, the translational success is likely to depend on the use of predictive tumor models in preclinical studies, simulating the complexity of the tumor microenvironment (e.g., the fibrotic extracellular matrix that impairs therapeutic outcomes) and stimulating tumor progression. This review compiles recent advances in the field of antitumor lipid-based nanoparticles and highlights emerging therapeutic approaches (e.g., mechanotherapy) to modulate tumor stiffness and improve T cell infiltration, and the use of organoids to better guide therapeutic outcomes. The implementation of advanced preclinical models such as tumor organoids, incorporating immune system cells and tumor extracellular matrix, will contribute to the development of innovative antitumor therapies such as mechanotherapy-assisted lipid-based immunotherapy.image

Automated summary

The application of lipid-based nanoparticles shows potential for cancer therapy, but its use in delivering drugs to solid tumors is limited. Instead, using lipid-based nanoparticles to remotely activate immune system responses is an emerging effective strategy. Overcoming challenges such as tumor heterogeneity and ineffective penetration of activated T cells within the tumor is necessary for the successful translation of this approach. Implementing advanced preclinical models, such as tumor organoids, will contribute to the development of innovative antitumor therapies.