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.

Background The prognostic value of loss of Krüppel-like factor 4 (KLF4) expression in digestive system cancers has not reached a consensus. This study aimed for a comprehensive investigation of the internal associations between KLF4 expression loss and prognostic implications in patients with digestive system cancers. Methods We searched for all relevant literatures in the electronic databases until February 1, 2017. The degree of association between KLF4 and prognosis was evaluated by pooled hazard ratios (HRs) as well as relevant 95% confidence intervals (95% CIs). Results Seventeen eligible studies with 2118 patients revealed that loss of KLF4 expression was connected with poor prognosis, with the pooled HRs of 1.61 (95% CI: 1.17–2.20, P = 0.003) for the overall survival (OS) and 1.99 (95% CI: 1.12–3.52, P = 0.001) for the disease-free survival (DFS)/recurrence-free survival (RFS)/metastasis-free survival (MFS). Additionally, loss of KLF4 expression was also related to a worse disease-special survival (DSS) yielding a pooled HR of 1.73 (95% CI: 1.08–2.77, P = 0.022). Conclusion Our findings suggest that loss of KLF4 expression is correlated with a bad outcome in most digestive system cancers, apart from esophagus squamous cell carcinoma (ESCC).

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