Glucose-Regulated Protein 78 Targeting ICG and DOX Loaded Hollow Fe₃O₄ Nanoparticles for Hepatocellular Carcinoma Diagnosis and Therapy

Abstract

Purpose

Liver cancer is considered as the third leading cause of cancer-related deaths, with hepatocellular carcinoma (HCC) accounting for approximately 90% of liver cancers. Improving the treatment of HCC is a serious challenge today. The primary objective of this study was to construct SP94-Fe₃O₄@ICG&DOX nanoparticles and investigate their potential diagnosis and treatment effect benefits on HCC.

Methods

Firstly, we synthesized and characterized SP94-Fe₃O₄@ICG&DOX nanoparticles and confirmed their in vitro release behavior, photothermal and photodynamic performance. Moreover, the in vivo imaging capability was also observed. Finally, the inhibitory effects on Hepa1-6 in vitro and in vivo were observed as well as biosafety.

Results

SP94-Fe₃O₄@ICG&DOX nanoparticles have a size of ~22.1 nm, with an encapsulation efficiency of 45.2% for ICG and 42.7% for DOX, showing excellent in vivo MPI and fluorescence imaging capabilities for precise tumor localization, and synergistic photo-chemotherapy (pH- and thermal-sensitive drug release) against tumors under irradiation. With the assistance of a fluorescence molecular imaging system or MPI scanner, the location and contours of the tumor were clearly visible. Under a constant laser irradiation (808 nm, 0.6 W/cm²) and a set concentration (50 µg/mL), the temperature of the solution could rapidly increase to ~45 °C, which could effectively kill the tumor cells. It could be effectively uptaken by HCC cells and significantly inhibit their proliferation under the laser irradiation (100% inhibition rate for HCC tumors). And most importantly, our nanoparticles exhibited favorable biocompatibility with normal tissues and cells.

Conclusion

This versatile agent can serve as an intelligent and promising nanoplatform that integrates multiple accurate diagnoses, precise positioning of cancer tissue, and effective coordination with synergistic tumor photodynamic therapy.

Graphical Abstract

Keywords:

• porous hollow structure
• magnetic particle imaging
• fluorescence imaging
• synergistic treatment
• theranostics

Data Sharing Statement

The data used and/or analyzed during this study are available from the corresponding author upon reasonable request.

Ethics Approval and Consent to Participate

All animal studies were performed in accordance with the guidelines of the Institutional Animal Care and Use Committee of the Institute of Automation, Chinese Academy of Sciences (permit no. IA21-2203-24). Consent for participation was not applicable.

Acknowledgments

This study was financially supported by the National Natural Science Foundation of China (Grant No.82072098).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this study.