iRGD Peptide-Mediated Liposomal Nanoparticles with Photoacoustic/Ultrasound Dual-Modality Imaging for Precision Theranostics Against Hepatocellular Carcinoma

Abstract

Purpose Prepare a multifunctional ultrasound molecular probe, cell-penetrating peptide-modified 10-hydroxycamptothecin-loaded phase-transformation lipid nanoparticles (iRGD-ICG-10-HCPT-PFP-NPs), and to combine iRGD-ICG-10-HCPT-PFP -NPs with low-intensity focused ultrasound (LIFU) for precision theranostics against hepatocellular carcinoma (HCC). Materials and Methods The morphology of nanoparticles (NPs) and iRGD-ICG-10-HCPT-PFP-NPs was detected. In vitro, we examined targeting ability by flow cytometry and confocal laser scanning microscopy (CLSM), assessed penetration ability into hepatoma cells, and assessed killing ability. In vivo, we examined the targeting ability of the NPs with a photoacoustic (PA) imager and fluorometer (FL), while LIFU irradiation was used to trigger the release of chemotherapeutic drugs, which had a therapeutic effect on tumors. Results The particle size of iRGD-ICG-10-HCPT-PFP-NPs was 298.4 ± 10.42 nm. In vitro, iRGD-ICG-10-HCPT-PFP-NPs bound more to SK-Hep1 cells than ICG-10-HCPT-PFP-NPs. iRGD-ICG-10-HCPT-PFP-NPs could achieve PA/ultrasound imaging. The percentage of antiproliferative and apoptotic cells in the iRGD-ICG-10-HCPT-PFP-NPs+LIFU group was significantly higher. In vivo, iRGD-ICG-10-HCPT-PFP-NPs can target tumor sites and achieve PA/ultrasound imaging. The tumor volume in the iRGD-ICG-10-HCPT-PFP-NPs+LIFU group was significantly smaller, and the antiproliferative and proapoptotic effects were higher. Conclusion We successfully prepared a novel molecular probe that has good targeting, can perform ultrasound/PA dual-modality imaging, and can penetrate deep into tumors to achieve better therapeutic tumor effects, providing a new idea and method for theranostics of HCC.

Advances in Antitumor Nano-Drug Delivery Systems of 10-Hydroxycamptothecin

“…The NPs with ultrasound/PA dual-modality imaging capability could penetrate deeply into the tumor and release the drug under LIFU irradiation. 113 Stearyl glycyrrhetinate (SG) is a derivative of GA. It has been demonstrated that GA and its derivatives may be used as ligands targeting the liver.…”

Visualization system based on hierarchical targeting for diagnosis and treatment of hepatocellular carcinoma

“…Nanocarriers were synthesized following the previously reported thin-film hydration method and phacoemulsification method [ 38 ]. First, DPPC 5 ​mg, DSPE-PEG2000-Mal 2 ​mg, cholesterol 1 ​mg, and 20 ​μL Fe 3 O 4 were added to a round-bottom flask and dissolved in 5 ​mL trichloromethane.…”

“…The CCK-8 assay was used to detect the cytotoxicity of MNDs to Huh7 and mMNDs to Hepa1-6. The specific method was the same as the previous study [ 38 ].…”

“…The method used to examine the efficacy of secondary targeting in vitro was same as that used in our previous reports [ 38 ]. We chose Huh7 and L02 ​cells to simulate human-derived tests and Hepa 1–6 and AML12 to simulate murine-derived tests.…”

Optical Microscopy Systems for the Detection of Unlabeled Nanoparticles

“… 129 As theranostics against hepatocellular carcinoma, Li et al constructed a multifunctional molecular probe from iRGD-modified phase transformation lipid nanoparticles loaded with the chemotherapeutic agent 10-hydroxycamptothecin. 130 The NPs demonstrated their suitability for dual ultrasound/PA imaging and the ability of tumor targeting, deep penetration into the tumor, and drug release under focused low-intensity ultrasound.…”