The immune-chemo-embolization effect of temperature sensitive gold nanomedicines against liver cancer

Although transcatheter arterial chemo-embolization(TACE)plays a key role on clinical treatment of hepatocellular carcinoma(HCC),it was greatly limited by the poor synergistic effect between chemotherapeutics and physical embolization to tumor-feeding arteries.In the present work,a temperature sensitive polymer poly(N-isopropylacrylamide-b-methacrylic acid)(PNA),which was modified with gold nanoparticles(AuNP@PNA),was successfully used to encapsulate doxorubicin(DOX)by electrostatic binding with their carboxyl groups.The resultant gold nanomedicines(AuNP@PNA/DOX)exhibited temperature responsive sol-gel phase transition,favorable shear thinning effect and X-ray angiography.By in vivo evaluation of vascular embolization on VX2-tumor-bearing rabbits,AuNP@PNA/DOX exhibited far better antitumor efficacy than Lipiodol/DOX,on either tumor growth inhibition,proliferation,apoptosis,necrosis or anti-metastasis.Owing to sufficient embolization to tumor vascular networks,AuNP@PNA/DOX down-regulated the expression levels of HIF-1α,VEGF and MMP-9,and prompted more efficient activation on CD3+/CD8+T cells and the related cytokines,suggesting the synergistic effect between AuNP@PNA and DOX on the improvement of post-operative tumor immunosuppressive microenvironment.With their favorable pharmcokinetics and biocompatibility,AuNP@PNA/DOX is promising to be developed as a multi-functional artery-imaging/embolic agent with immune-chemo-embolization for enhancing TACE efficacy on HCC.

Clinical study of different interventional treatments for primary hepatocellular carcinoma based on propensity-score matching

BACKGROUND Transcatheter arterial chemoembolization(TACE)is the main treatment for patients with primary hepatocellular carcinoma(PHC)who miss the opportunity to undergo surgery.Conventional TACE(c-TACE)uses iodized oil as an embolic agent,which is easily washed by blood and affects its efficacy.Drug-eluting bead TACE(DEB-TACE)can sustainably release chemotherapeutic drugs and has a long embolization time.However,the clinical characteristics of patients before the two types of interventional therapies may differ,possibly affecting the conclusion.Only a few studies have compared these two interventions using propensity-score matching(PSM).AIM To analyze the clinical effects of DEB-TACE and c-TACE on patients with PHC based on PSM.METHODS Patients with PHC admitted to Dangyang People’s Hospital(March 2020 to March 2024)were retrospectively enrolled and categorized into groups A(DEB-TACE,n=125)and B(c-TACE,n=106).Sex,age,Child-Pugh grade,tumor-node-meta-stasis stage,and Eastern Cooperative Oncology Group score were selected for 1:1 PSM.Eighty-six patients each were included post-matching.Clinical efficacy,liver function indices(aspartate aminotransferase,alanine aminotransferase,total bilirubin,and albumin),tumor serum markers,and adverse reactions were compared between the groups.RESULTS The objective response and disease control rates were significantly higher in group A(80.23%and 97.67%,respectively)than in group B(60.47%and 87.21%,respectively)(P<0.05).Post-treatment levels of aspartate aminotransferase,alanine aminotransferase,and total bilirubin were lower in group A than in group B(P<0.05),whereas post-treatment levels of albumin in group A were comparable to those in group B(P>0.05).Post-treatment levels of tumor serum markers were significantly lower in group A than in group B(P<0.05).Patients in groups A and B had mild-to-moderate fever and vomiting symptoms,which improved with conservative treatment.The total incidence of adverse reactions was significantly higher in group B(22.09%)than in group A(6.97%)(P<0.05).CONCLUSION DEB-TACE has obvious therapeutic effects on patients with PHC.It can improve liver function indices and tumor markers of patients without increasing the rate of liver toxicity or adverse reactions.