Precision Nanotherapy for p53-Mutant Cancer Using Modular Triple-LNP Delivery

This study introduces a novel modular lipid nanoparticle (LNP) platform designed to combat cancers driven by mutant TP53 (p53)—one of the most pervasive genetic alterations in malignancies. The system integrates three mechanistically distinct LNPs: one delivering proteolysis-targeting chimeras (PROTACs) for targeted degradation of mutant p53, another encapsulating the small molecule APR-246 to restore wild-type p53 conformation, and a third carrying IL-15 mRNA plus a STING agonist to activate innate and adaptive anti-tumor immunity. Using in silico simulations of over 3,000 virtual patients across six cancer types (non-small cell lung, triple-negative breast, pancreatic, colon, glioblastoma, and melanoma), I evaluated therapeutic outcomes including remission rates, metastasis suppression, immune activation, resistance evolution, and safety. The triple-LNP therapy demonstrated synergistic efficacy, with higher remission and lower relapse than single-agent or conventional treatments. Tumor volumes shrank rapidly, metastatic spread was curtailed, and adaptive resistance was delayed by incorporating a maintenance dosing phase. Simulated safety profiles showed minimal systemic toxicity due to the modular design’s targeted delivery and controlled cytokine release. I present clear graphs of tumor regression, immune activation metrics, dosing schedules, and pharmacokinetic profiles to illustrate the therapeutic profile. Compared to standard chemotherapy, the triple-LNP platform yielded superior efficacy with reduced toxicity and relapse. I also discuss formulation methods (e.g. microfluidic LNP synthesis, PEGylation for stealth), safety mechanisms to avoid cytokine storms, and regulatory pathways toward clinical translation. These results provide a comprehensive preclinical blueprint for a multi-component nanotherapy to address the complex challenges of p53-mutant cancers.