Data from A Virus-Inspired Inhalable Liponanogel Induces Potent Antitumor Immunity and Regression in Metastatic Lung Tumors

• DOI: 10.1158/0008-5472.c.7348811
• Publication Date: 2024-07-15T07:28:08Z
• Authors: Junyao Li; Lanqing Luo; Jia He; Jinchao Yu; Xinyan Li; Xueying Shen; Junxia Zhang; Sai Li; Jeffrey M. Karp; Rui Kuai

<div>Abstract<p>Pulmonary delivery of immunostimulatory agents such as poly(I:C) to activate double-stranded RNA sensors MDA5 and RIG-I within lung-resident antigen-presenting cells is a potential strategy enhance antitumor immunity by promoting type I interferon secretion. Nevertheless, following pulmonary delivery, suffers from rapid degradation poor endosomal escape, thus limiting its potency. Inspired the structure virus that utilizes internal viral proteins tune loading cytosolic nucleic acids, we developed liponanogel (LNG)–based platform overcome challenges poly(I:C). The LNG comprised an anionic polymer hyaluronic acid–based nanogel core coated lipid shell, which served protective layer stabilize in lungs. was protonated acidic endosomes membrane permeability After LNG-poly(I:C) induced 13.7-fold more IFNβ than alone two-fold loaded state-of-art nanoparticles [LNP-poly(I:C)]. Additionally, potent CD8<sup>+</sup> T-cell stronger therapeutic effects LNP-poly(I:C). combination PD-L1 targeting led regression established lung metastases. Due ease manufacturing high biocompatibility LNG, may be broadly applicable treatment different tumors spur development innovative strategies for cancer immunotherapy.</p><p><b>Significance:</b> Pulmonary with virus-inspired inhalable strongly activates stimulates immunity, representing promising safe effective metastatic tumors.</p></div>