Citation: Hang Xiao, Hongyu Zhong, Shiqi Yang, Kunwei Li, Jing Su, Faisal Raza, Mingfeng Qiu. Folic acid-modified erythrocyte membrane enhances targeted delivery of biomimetic nanoplatforms for hepatocellular carcinoma therapy[J]. Chinese Chemical Letters, ;2026, 37(9): 111937. doi: 10.1016/j.cclet.2025.111937 shu

Folic acid-modified erythrocyte membrane enhances targeted delivery of biomimetic nanoplatforms for hepatocellular carcinoma therapy

School of Pharmaceutical Science, Shanghai Jiao Tong University, Shanghai 200240, China

faisalraza@sjtu.edu.cn

mfqiu@sjtu.edu.cn

Received Date: 21 July 2025
Revised Date: 30 September 2025
Accepted Date: 8 October 2025
Available Online: 10 October 2025

Figures(4)

Liver cancer, particularly hepatocellular carcinoma (HCC), is a leading cause of cancer-related mortality worldwide. The therapeutic potential of norcantharidin (NCTD), a small-molecule chemotherapeutic agent, is often limited by its rapid systemic clearance and dose-dependent nephrotoxicity. Here, a novel folic acid (FA)-modified erythrocyte membrane (EM)-coated nanoplatform (FA/EM@PEI-NCTD) was developed to improve tumor targeting, prolong circulation, and mitigate renal toxicity. This nanoplatform preserves CD47 expression, transmitting “don't eat me” signal to evade macrophage uptake. In vitro, FA/EM@PEI-NCTD showed enhanced cytotoxicity against HCC cells and favorable drug release kinetics with low hemolytic activity. In vivo, the system demonstrated superior tumor targeting, growth inhibition, prolonged survival, and reduced nephrotoxicity. Mechanistically, the treatment promoted apoptosis in H22 cells by upregulating Bax and caspase-3 while downregulating Bcl-2. These results highlight FA/EM@PEI-NCTD as a promising strategy for safe and effective targeted HCC therapy.
- Liver cancer,
- Norcantharidin,
- Polyethylenimine,
- Erythrocyte membrane,
- Folic acid
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