DNA Repair Enzyme Regulation Strategy for Enhanced Pancreatic Neuroendocrine Tumor Therapy via Targeting siRNA-Lipid Nanoparticles
-methylguanine-DNA methyltransferase (MGMT). This resistance limits the long-term efficacy of TMZ in many patients. To overcome these challenges, we developed the lipid nanoparticles (LNPs) modified with somatostatin receptors (SSTRs) targeting peptide of Octreotide to codeliver the TMZ and MGMT-siRNA (LOTR) to improve the therapeutic efficacy of TMZ via inhibiting MGMT-mediated resistance and also reducing systemic toxicity caused by TMZ. The in vitro and in vivo results demonstrated that the LOTR system significantly sensitized the tumor response to TMZ, lowered drug resistance, and reduced off-target effects, offering a promising approach for the treatment of advanced panNETs.
Authors
- Wenda Tang (ORCID: https://orcid.org/0000-0001-6684-4642)
- Xin Lou (ORCID: https://orcid.org/0000-0002-6715-0375)
- Guixiong Fan (ORCID: https://orcid.org/0009-0004-3995-612X)
- Weibo Cai (ORCID: https://orcid.org/0000-0003-4641-0833)
- Xiaowu Xu
- Desheng Jing
- Fei Wang
- Junfeng Xu
- Jie Chen
- Yan Li
- Xianjun Yu
- Zhongmin Tang
- Shunrong Ji
Institutions
- Tongji University (CN)
- Shanghai Medical College of Fudan University (CN)
- Fudan University (CN)
- Cancer Institute (WIA) (IN)
- Fudan University Shanghai Cancer Center (CN)
- Frontier Science Foundation (CH)
- Shanghai Cancer Institute (CN)
- Precision for Medicine (United States) (US)
- Shanghai Tenth People's Hospital (CN)
Publication Details
- Journal
- ACS Nano
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1021/acsnano.5c21452
- Primary Topic
- Neuroendocrine Tumor Research Advances
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Natural Science Foundation of Shanghai
- Shanghai Municipal Health Commission
- National Natural Science Foundation of China
- Fudan University
- Science and Technology Commission of Shanghai Municipality
- Fundamental Research Funds for the Central Universities