iBoost is a lipid nanoparticle formulation designed to retain payloads in the tumor microenvironment (TME). In a mouse model of peritoneal metastasis of colon cancer, iBoost largely focuses Resiquimod, a TLR agonist, to the antigen presenting cells (APCs) in the peritoneum while delaying its systemic absorption. As a result, iBoost increases the release of IFN-alpha in the TME. iBoost promotes T-cell priming to CD4+ and CD8+ T cells and potentiates the antitumor efficacy against this aggressive tumor model in combination with Oxaliplatin, a chemo drug. This new combination therapy is safe and effective in this model, curing 60-70% of the mice. Additionally, iBoost serves as an in-situ cancer vaccine. No cancer growth was observed in the cured mice post tumor re-challenge, suggesting the development of specific immunity, which provides great potential for cancer immunotherapy.