Omvs-Mm Hybrid Membrane Biomimetic Ultrasonic Phase Change Nanoparticles in the Treatment of Colorectal Cancer Liver Metastasis

Abstract

Patients with colorectal cancer liver metastasis (CRLM) are characterized by scattered, multiple, and microscopic lesions, and the vast majority of them cannot be radically resected, so chemotherapy is predominantly employed in clinical settings to prolong patient survival. However, the long-term use of chemotherapeutic agents can lead to systemic toxicity and induce drug resistance, resulting in unsatisfactory therapeutic outcomes. In this study, we extracted outer membrane vesicles (OMVs) from Escherichia coli and macrophage membranes (MM) to develop a kind of OMVs-MM hybrid membrane biomimetic ultrasonic phase change nanoparticles (O/M-5-FU-NPs). These nanoparticles were designed to encapsulate the chemotherapeutic agent 5-fluorouracil (5-FU) while leveraging the targeting capabilities of MM for specific delivery and accumulation within tumor sites. By employing ultrasound-targeted microbubble destruction technology, the release of both OMVs and 5-FU was facilitated effectively, thereby enhancing the tumor-killing efficacy of 5-FU alongside amplifying the anti-tumor immune response elicited by OMVs. This approach aims to achieve precise targeting in the treatment of CRLM, establish a synergistic system that integrates immunotherapy with chemotherapy, and provide a promising clinical solution for cancer management.

Note:
Funding declaration: This work was supported by National Natural Science Foundation of China (Grant Nos. U22A20346), Heilongjiang Provincial Key Research and Development Program (Grant Nos. GA21D007), National Natural Science Foundation of China (Grant Nos. 82402283), Heilongjiang Provincial Postdoctoral Science Foundation (Grant Nos. LBH-Z23237), Heilongjiang Provincial Postdoctoral Science Foundation (Grant Nos. LBHZ23229)

Conflict of Interests: The authors declare no conflict of interest.

Ethical Approval: This experiment was approved by the Animal Management and Use Ethics Committee of the Second Affiliated Hospital of Harbin Medical University (Ethics Number: YJSDW2022-029).

Keywords: OMVs, Biomimetic nanoparticles, Ultrasonic phase change, UTMD, CRLM