Ultrasound-activated macrophage-bomb for enhanced imaging and drug delivery in hepatocellular carcinoma

Qian Yan; Jiayu Yang; Yubin Chen; Qianlong Wu; Xinqiang Xu; Jie Zhang; Shiye Ruan; Yifeng Cai; Chengjun Sun; Sheng Chen; Zhongyan Zhang; Jinwei Cui; Jike Fang; Chuanzhao Zhang; Baohua Hou; Qi Zhou; Shanzhou Huang

Materials & Design (Aug 2024)

Ultrasound-activated macrophage-bomb for enhanced imaging and drug delivery in hepatocellular carcinoma

Qian Yan,
Jiayu Yang,
Yubin Chen,
Qianlong Wu,
Xinqiang Xu,
Jie Zhang,
Shiye Ruan,
Yifeng Cai,
Chengjun Sun,
Sheng Chen,
Zhongyan Zhang,
Jinwei Cui,
Jike Fang,
Chuanzhao Zhang,
Baohua Hou,
Qi Zhou,
Shanzhou Huang

Affiliations

Qian Yan: School of Medicine South China University of Technology, Guangzhou 51000, China; Department of General Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Jiayu Yang: Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Guangzhou 510080, China
Yubin Chen: School of Medicine South China University of Technology, Guangzhou 51000, China
Qianlong Wu: Heyuan People’s Hospital, Heyuan 517000, China
Xinqiang Xu: Heyuan People’s Hospital, Heyuan 517000, China
Jie Zhang: Heyuan People’s Hospital, Heyuan 517000, China
Shiye Ruan: The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
Yifeng Cai: Department of General Surgery, Hui Ya Hospital of the First Affiliated Hospital, Sun Yat-Sen University, Huizhou, Guangdong 516081, China; Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
Chengjun Sun: Department of Organ Transplantation, Guangdong Provincial People’s Hospital, Guangzhou 510080, China
Sheng Chen: Department of General Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
Zhongyan Zhang: Department of General Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
Jinwei Cui: School of Medicine South China University of Technology, Guangzhou 51000, China
Jike Fang: School of Medicine South China University of Technology, Guangzhou 51000, China
Chuanzhao Zhang: School of Medicine South China University of Technology, Guangzhou 51000, China; Department of General Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China; Corresponding authors at: Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 51000, China (C. Zhang, B. Hou, S. Huang); Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China (Q. Zhou).
Baohua Hou: Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Guangzhou 510080, China; Heyuan People’s Hospital, Heyuan 517000, China; Corresponding authors at: Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 51000, China (C. Zhang, B. Hou, S. Huang); Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China (Q. Zhou).
Qi Zhou: Department of General Surgery, Hui Ya Hospital of the First Affiliated Hospital, Sun Yat-Sen University, Huizhou, Guangdong 516081, China; Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Corresponding authors at: Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 51000, China (C. Zhang, B. Hou, S. Huang); Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China (Q. Zhou).
Shanzhou Huang: School of Medicine South China University of Technology, Guangzhou 51000, China; Department of General Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China; Corresponding authors at: Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 51000, China (C. Zhang, B. Hou, S. Huang); Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China (Q. Zhou).

Journal volume & issue: Vol. 244
p. 113202

Abstract

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In the context of hepatocellular carcinoma (HCC) treatment, this study introduces a biomimetic “bomb” approach to target HCC by utilizing macrophages (MAs) as ultrasound-responsive carriers. This advanced biomimetic drug delivery system (MAs-DOX/PFP/Ms, MAs-DPM) encapsulates doxorubicin (DOX) and perfluoropentane (PFP) and is designed to precisely target HCC. MAs-DPM exhibits excellent drug loading capacity and biocompatibility, can effectively release DOX and enhance ultrasound imaging capabilities under ultrasound irradiation (UI). Experiments confirmed that MA maintained its biological activity and vitality during co-incubation and phagocytosis with DOX-loaded DPM, and microscopy confirmed that MA effectively engulfed DPM without changing cell morphology or function. Transwell experiments demonstrated that this bionic “bomb” (MAs-DPMs) not only retained the tumor targeting ability of macrophages, but also successfully delivered therapeutic drugs to tumor cells. Compared with samples without UI treatment, UI significantly increased the release of DOX from MAs-DPM, enhanced the drug release rate and inhibited the growth of HCC cells. Live/Dead staining experiments further intuitively revealed the precise “biobomb” effect of MAs-DPM under UI, effectively proving its ability to inhibit HCC cell proliferation. In vivo studies demonstrated that MAs-DPM was able to proficiently localize tumor sites within 24 h. Furthermore, the ultrasound-mediated phase transition of PFP enhanced the imaging efficacy, confirming the feasibility of macrophage-mimicking biological bombs for real-time in vivo ultrasound tracking. In the tumor-bearing nude mouse model, UI-treated MAs-DPMs remarkably delayed tumor growth and prolonged survival time compared with other groups. Subsequent histological and serum index evaluation further confirmed the in vivo safety of MAs-DPMs, and UI-treatment did not induce significant histological or pathological changes or statistical differences in vital organ or serum markers. These experiment results highlight the great potential of MAs-DPM as a strategic approach for the diagnosis and treatment of HCC.

Published in Materials & Design

ISSN: 0264-1275 (Print); 1873-4197 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials
Website: https://www.journals.elsevier.com/materials-and-design

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