Background
The efficacy of systemic chemotherapy for hepatocellular carcinoma (HCC) is predominantly hampered by low accumulation in tumor tissue and the high systemic toxicity of anticancer drugs. In this study, we designed an in situ drug-loaded injectable thermosensitive hydrogel system for the simultaneous delivery of norcantharidin-loaded nanoparticles (NCTD-NPs) and doxorubicin (Dox) via intratumoral administration to HCC tumors.
Methods
NCTD-NPs were prepared by the thin film dispersion method using PCEC polymers as the carrier. Then, NCTD-NPs and Dox were co-encapsulated in a thermosensitive hydrogel based on Pluronic F127 (PF127) to construct a dual drug-loaded hydrogel system. The rheological properties of the drug-loaded hydrogel were studied using a rheometer. Drug release of the drug-loaded hydrogel and cytotoxicity in HepG2 cells were evaluated in vitro. An H22 tumor-bearing mice model was used to assess the in vivo antitumor activity of the drug-loaded hydrogel via intratumoral administration.
Results
The prepared drug-loaded hydrogel exhibited good thermal-sensitive properties, which remained liquid at room temperature and rapidly transformed into a non-flowing gel at body temperature, and released the drugs in a sustained manner. In vitro studies revealed that the drug-loaded hydrogel exhibited remarkable antiproliferative activity in HepG2 cells compared to free drugs. In vivo antitumor efficacy experiments showed that the drug-loaded hydrogel significantly suppressed tumor growth, alleviated side effects, and prolonged the survival time of mice bearing H22 tumors compared to the other groups. Moreover, immunohistochemical staining revealed that the expression of Ki-67 and CD31 in the drug-loaded hydrogel group was significantly lower than that in the other groups (P < 0.05), indicating that the drug-loaded hydrogel effectively inhibited tumor proliferation and angiogenesis.
Conclusion
The formulated hybrid thermosensitive hydrogel system with sustained drug release and enhanced therapeutic efficacy was demonstrated to be a promising strategy for the local-regional treatment of HCC via intratumoral administration.
We developed a computer-aided diagnosis (CAD) system based on linked color imaging (LCI) images to predict the histological results of polyps by analyzing the colors of the lesions. A total of 139 images of adenomatous polyps and 69 images of non-adenomatous polyps obtained from our hospital were collected and used to train the CAD system. A test set of LCI images, including both adenomatous and non-adenomatous polyps, was prospectively collected from patients who underwent colonoscopies between Oct and Dec 2017; this test set was used to assess the diagnostic abilities of the CAD system compared to those of human endoscopists (two experts and two novices). The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of this novel CAD system for the training set were 87.0%, 87.1%, 87.0%, 93.1%, and 76.9%, respectively. The test set included 115 adenomatous polyps and 66 non-adenomatous polyps that were prospectively collected. The CAD system identified adenomatous or non-adenomatous polyps in the test set with an accuracy of 78.4%, a sensitivity of 83.3%, a specificity of 70.1%, a PPV of 82.6%, and an NPV of 71.2%. The accuracy of the CAD system was comparable to that of the expert endoscopists (78.4% vs 79.6%;
p
= 0.517). In addition, the diagnostic accuracy of the novices was significantly lower to the performance of the experts (70.7% vs 79.6%;
p
= 0.018). A novel CAD system based on LCI could be a rapid and powerful decision-making tool for endoscopists.
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