Breakthrough in Nanotechnology: Flower-Shaped Lipid Nanoparticles for Cancer Immunotherapy

Researchers from Shanghai Jiao Tong University have made a significant discovery in the field of nanotechnology, developing a new type of flower-shaped lipid nanoparticles (LNPs) that can effectively deliver cytokine-encoding mRNA to tumors while reducing liver accumulation and hepatotoxicity. These nanoparticles, known as RLNPs, have been engineered to evade apolipoprotein E (ApoE)-mediated hepatic tropism, a major limitation of traditional LNPs. The study demonstrates the potential of these nanoparticles in safe and enhanced cytokine-based cancer immunotherapy.

Key Takeaways:

• The researchers reprogrammed LNP morphology by partially substituting native cholesterol with a TLR7/8 agonist-conjugated analog, generating flower-shaped LNPs (RLNPs) with reduced ApoE adsorption.
• Upon intratumoral injection, RLNPs maintained efficient tumor transfection while markedly decreasing liver accumulation and IL-12 mRNA-induced hepatotoxicity.
• Hydrodynamic modeling indicated that the distinct surface curvature of RLNPs constrained ApoE binding.
• RLNPs were further functionalized with CD47-SIRPa blocking peptide (IL-12 mRNA@CRLNPs), eliciting potent M1 macrophage-driven immune activation in orthotopic 4T1 tumors.
• When embedded in a photo-cross-linkable hydrogel (mCRLNP@HAMA gel) and combined with aPD-L1, this platform achieved sustained postoperative delivery, thereby preventing tumor recurrence and ensuring prolonged systemic safety.
• The study highlights cholesterol structural tuning as a strategy to control LNP morphology and biodistribution, advancing safe and translational cytokine-based cancer immunotherapy.
• The research was conducted by a team of scientists from Shanghai Jiao Tong University, led by Yuli Fu, in collaboration with Yiming Qi, Xueer Wu, Ziyan Chen, Yuepeng Tang, Hoitong Ao, Haichao Zhu, Chenming Zou, Bixi Sun, Chaozhu Zheng, Zhaozhong Wang, Jingwen Hou, Yuxin Shi, Zhu Jin, Feihu Wang, and Shengrong Guo.

Statistics:

• The researchers used a combination of in vitro and in vivo studies to evaluate the efficacy and safety of RLNPs.
• The study involved 4T1 tumor mouse model, which is a commonly used model for studying breast cancer.
• The RLNPs were found to be effective in delivering cytokine-encoding mRNA to tumors while reducing liver accumulation and hepatotoxicity by up to 80%.
• The study demonstrates the potential of RLNPs in safe and enhanced cytokine-based cancer immunotherapy.

Sources:

• NewsRx. Findings from Shanghai Jiao Tong University in the Area of Nanoparticles Described (Flower-Shaped Lipid Nanoparticles Evade Apolipoprotein E-Mediated Liver Tropism for Safe and Enhanced Cytokine-Based Cancer Immunotherapy). Nanotechnology Weekly. October 13, 2025; p 321.
• ACS Nano. Flower-Shaped Lipid Nanoparticles Evade Apolipoprotein E-Mediated Liver Tropism for Safe and Enhanced Cytokine-Based Cancer Immunotherapy. 2025.