Inhibition of growth of hepatocellular carcinoma by co-delivery of anti-PD-1 antibody and sorafenib using biomimetic nano-platelets

BMC Cancer. 2024 Feb 26;24(1):273. doi: 10.1186/s12885-024-12006-1.

Abstract

Background: Traditional nanodrug delivery systems have some limitations, such as eliciting immune responses and inaccuracy in targeting tumor microenvironments.

Materials and methods: Targeted drugs (Sorafenib, Sora) nanometers (hollow mesoporous silicon, HMSN) were designed, and then coated with platelet membranes to form aPD-1-PLTM-HMSNs@Sora to enhance the precision of drug delivery systems to the tumor microenvironment, so that more effective immunotherapy was achieved.

Results: These biomimetic nanoparticles were validated to have the same abilities as platelet membranes (PLTM), including evading the immune system. The successful coating of HMSNs@Sora with PLTM was corroborated by transmission electron microscopy (TEM), western blot and confocal laser microscopy. The affinity of aPD-1-PLTM-HMSNs@Sora to tumor cells was stronger than that of HMSNs@Sora. After drug-loaded particles were intravenously injected into hepatocellular carcinoma model mice, they were demonstrated to not only directly activate toxic T cells, but also increase the triggering release of Sora. The combination of targeted therapy and immunotherapy was found to be of gratifying antineoplastic function on inhibiting primary tumor growth.

Conclusions: The aPD-1-PLTM-HMSNs@Sora nanocarriers that co-delivery of aPD-1 and Sorafenib integrates unique biomimetic properties and excellent targeting performance, and provides a neoteric idea for drug delivery of personalized therapy for primary hepatocellular carcinoma (HCC).

Keywords: Immunotherapy; Nanoparticles; Platelet membrane; Sorafenib; Tumor microenvironment.

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Biomimetics
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / pathology
  • Mice
  • Nanoparticles*
  • Sorafenib / therapeutic use
  • Tumor Microenvironment

Substances

  • Sorafenib
  • Antineoplastic Agents