Lipid nanoparticle-based multi-scale systemic immune programming for cancer therapy.

Document Type

Article

Publication Date

11-4-2026

Identifier

DOI: 10.1016/j.ymthe.2026.08.007

Abstract

The clinical reach of cancer immunotherapy is currently limited by off-target toxicity, physical barriers in solid tumors, and the complex manufacturing of personalized cell therapies. This review presents multi-scale systemic immune programming as a transformative approach, in which lipid nanoparticles (LNPs) function not merely as delivery vehicles but as programmable platforms that direct immune responses across biological scales. At the molecular and cellular levels, LNP design and intracellular delivery regulate mRNA stability, translation, and antigen presentation. At the tissue level, intratumoral mRNA delivery reprograms the tumor microenvironment to overcome stromal barriers and immunosuppression. At the systemic level, LNPs coordinate immune responses, including in vivo chimeric antigen receptor T cell (CAR-T) engineering and vaccine-driven immune memory. At the organismal level, liver-targeted LNPs restore metabolic regulators, reverse cachexia, and improve host resilience. Building on this framework, we propose a dual-track therapeutic paradigm that integrates tumor-directed immune activation with host physiological restoration. Together, this approach positions LNP-based therapies to treat cancer as a systemic immunometabolic disorder rather than a localized disease.

Journal Title

Molecular therapy : the journal of the American Society of Gene Therapy

Volume

34

Issue

11

First Page

6182

Last Page

6201

MeSH Keywords

Humans; Neoplasms; Nanoparticles; Animals; Lipids; Immunotherapy; Tumor Microenvironment; Cancer Vaccines; Liposomes

PubMed ID

42576384

Keywords

LNPs; cancer immunotherapy; cancer-associated cachexia; lipid nanoparticles; systemic immune programming

Link to Full Text
Library Record

Share

COinS