# Synergistic Gene Immunotherapy for Lung Cancer via Targeted Nanomedicine Restoring Genetic Tumor Suppression and Activating STING Pathway

## TL;DR

A new nanomedicine was developed to treat lung cancer by delivering a tumor suppressor gene and activating an immune pathway, showing promising results in targeting cancer cells.

## Contribution

A novel gene-immunotherapeutic nanomedicine (TGR-BLDHs) was developed for targeted NSCLC treatment by delivering TMEM163 and activating the STING pathway.

## Key findings

- TGR-BLDHs showed specific tumor suppression in NSCLC through targeted gene therapy.
- Activation of the cGAS/STING pathway by TGR-BLDHs enhanced antitumor effects in both antigen-presenting and cancerous cells.
- The nanomedicine inhibited tumor progression in vivo with biocompatibility.

## Abstract

Lung cancer, particularly
non-small cell lung cancer
(NSCLC), presents
significant therapeutic challenges due to its high mortality and complex
pathogenesis. General strategies, including chemotherapy, immunotherapy,
and even novel gene therapy, fail to provide comprehensive inhibition
against NSCLC individually. Here, a novel gene-immunotherapeutic nanomedicine,
pTMEM163/cGAMP@cRGD-BSA/LDHs (TGR-BLDHs), was developed by employing
cyclic Arg-Gly-Asp (cRGD)-modified bovine serum albumin/layered double
hydroxide (BSA-LDH) nanoparticles for targeted delivery of TMEM163,
a newly identified tumor suppressor gene (TSG) of NSCLC and cGAS/STING
agonist (cGAMP). TGR-BLDHs exhibited highly specific NSCLC tumor suppression
via desirable tumor-targeted TSG gene therapy. Meanwhile, TGR-BLDHs
successfully evoked potent antitumor effects by activating the cGAS/STING
pathway in both antigen-presenting and cancerous cells, eventually
inhibiting tumor progression in vivo. The current study highlighted
the potential of TGR-BLDHs for effective gene immunotherapy against
NSCLC with desirable tumor specificity and biocompatibility, offering
a promising gene-immunotherapeutic strategy for NSCLC.