The cooperative effect of p53 and Rb in local nanotherapy in a rabbit VX2 model of hepatocellular carcinoma

Dong, Shaohong; Qibin, Tang; Long, M. Louisa; Guan, Jian; Lu, Yao; Li, Gaopeng

doi:10.2147/ijn.s51353

Cited by 5 publications

(7 citation statements)

References 43 publications

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“…Rabbit hepatic VX2 carcinoma is a rapidly growing, hypervascular tumor that is mainly vascularized by the hepatic artery, similar to human hepatocellular carcinoma; thus, the hepatic VX2 carcinoma model has been increasingly used in recent years as a model for both HCC and interventional therapies. [37][38][39] In this study, after 2 weeks of tumor implantation, a superselective hepatic arteriogram showed obvious staining of the tumor in the left lobe of the liver and a rich blood supply (Figure 2A and C). After the injection of Bi-Ln NPs (Figure 2B), X-ray fluoroscopic images showed obvious Bi-Ln NPs aggregation in the tumor area.…”

Section: Dsa Imagingsupporting

confidence: 51%

<p>Transcatheter Intra-Arterial Infusion Combined with Interventional Photothermal Therapy for the Treatment of Hepatocellular Carcinoma</p>

Zhou

Ling

Cao

et al. 2020

IJN

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Background: Photothermal therapy (PTT) has great potential application in the treatment of tumors. However, due to the low penetration of near-infrared light (NIR) and the low concentration of nanomaterials in the tumor site, the application of PTT has been limited. Purpose: The objective of this study was to investigate the therapeutic effect of transcatheter intra-arterial infusion of lecithin-modified Bi nanoparticles (Bi-Ln NPs) combined with interventional PTT (IPTT) on hepatocellular carcinoma. Methods: Bi-Ln NPs were prepared by emulsifying the hydrophobic Bi nanoparticles and lecithin, and the photothermal conversion and cytotoxicity of Bi-Ln NPs were then measured by infrared imaging and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, respectively. Twenty-four VX2 hepatic carcinoma rabbits were randomly divided into four groups. Rabbits in group A received Bi-Ln NPs by intra-arterial infusion and NIR laser treatment (IA Bi-Ln NPs + Laser), group B received Bi-Ln NPs by intravenous infusion and NIR laser treatment (IV Bi-Ln NPs + Laser), group C received PBS (phosphate buffer saline) via intra-arterial infusion with NIR laser treatment (IA PBS + Laser), group D received PBS via intra-arterial infusion (IA PBS). Transcatheter intra-arterial infusion was conducted by superselective intubation under digital subtraction angiography (DSA) guidance. IPTT was performed by introducing an NIR optical fiber access to the rabbit VX2 hepatic carcinoma under real-time ultrasound guidance. Magnetic resonance imaging (MRI) was performed to evaluate the tumor size. Hematoxylin and eosin (H&E) stain and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were conducted 7 days after treatment to evaluate the necrosis rate and viability of tumor, respectively. Results: The Bi-Ln NPs have the advantages of good biological compatibility and high photothermal conversion efficiency. Minimally invasive transcatheter intra-arterial infusion can markedly increase the concentration of Bi-Ln NPs in tumor tissues. IPTT can contribute to the significant improvement in the photothermal efficiency of Bi-Ln NPs. Compared to other groups, the group of IA Bi-Ln NPs + Laser showed a significantly higher tumor inhibition rate (TIR) of 93.38 ± 19.57%, a higher tumor necrosis rate of 83.12 ± 8.02%, and a higher apoptosis rate of (43.26 ± 10.65%) after treatment. Conclusion: Transcatheter intra-arterial infusion combined with interventional PTT (IPTT) is safe and effective in eradicating tumor cells and inhibiting tumor growth and may provide a novel and valuable choice for the treatment of hepatocellular carcinoma in the future.

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Section: Dsa Imagingsupporting

confidence: 51%

<p>Transcatheter Intra-Arterial Infusion Combined with Interventional Photothermal Therapy for the Treatment of Hepatocellular Carcinoma</p>

Zhou

Ling

Cao

et al. 2020

IJN

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“…and kanamycin (100 mg/ml) at 37 °C in 5% CO2 humidified atmosphere. Plasmid DNA (pDNA) PEGFP-C2 and its wt-p53 containing subclone (PEGFP-C2-wt-p53) were prepared and investigated according to our former studies [1, 9, 10]. New zealand rabbits, female or male, weighing 2.5-3.5 kg at approximately 17 to 19 weeks of age, were obtained from the laboratory animal center of Shanxi medical university.…”

Section: Methodsmentioning

confidence: 99%

“…All the animal experiments and breeding were performed under conditions approved by the Ethics Committee of Shanxi medical university, in compliance with the NIH guidelines and items for care and use of laboratory animals and in accordance with the Chinese relevant legislation on animal use. The VX2 models were prepared according to procedures described in the former reports [1, 9, 10]. All the animals were operated under general anesthesia, intramuscular injection of 0.2 ml per kilo body weight Sumianxin (Quartermaster University of PLA, China), by a veterinary anesthetist.…”

Section: Methodsmentioning

confidence: 99%

“…pDNA with normal saline solution served as controls. The experiment details are according to our former reports [1, 9, 10]. (4): The nHAP/lipiodol and nanoplex/lipiodol W/O emulsions were prepared by emulsionizing 1 ml lipiodol and 1 ml nanoplexs (containing 3.75 mg various nHAP and 250 μg of pEGFPC2-wt-p53 pDNA), according to the pumping method in our former report, followed by storage at room temperature prior to the surgical procedure [1, 9, 10].…”

Section: Methodsmentioning

confidence: 99%

“…Wild-type p53 (wt-p53) is a house-keeping tumour suppressor that is frequently mutated and disfunctional in more than 50% of HCCs. Former study [1, 9, 10] successfully combined wt-p53 gene therapy, transcatheter arterial embolization (TAE) and antitumoral nanoparticle for hepatoma by exploiting poly-lysine modified hydroxyapatite nanoparticles (Pll-nHAP) to serve as both embolic material and therapeutic target gene vector at the same time. Unfortunately, ideal transfection activity and completely tumor eradication were not achieved and necessitate further improvements.…”

Section: Introductionmentioning

confidence: 99%

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Synergism of wt-p53 and synthetic material in local nano-TAE gene therapy of hepatoma: comparison of four systems and the possible mechanism

Kang

Jin

et al. 2019

BMC Cancer

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BackgroundTAE-gene therapy for hepatoma, incorporating the tumor-targeted therapeutic efficacy of trans-arterial embolization, hydroxyapatite nanoparticles (nHAP) and anti-cancer wild-type p53 gene (wt-p53), was presented in our former studies (Int J Nanomedicine 8:3757-68, 2013, Liver Int 32:998-1007, 2012). However, the incompletely antitumoral effect entails defined guidelines on searching properer materials for this novel therapy.MethodsUnmodified nHAP, Ca(2+) modified nHAP, poly-lysine modified nHAP and liposome were separately used to form U-nanoplex, Ca-nanoplex, Pll-nanoplex, L-nanoplex respectively with wt-p53 expressing plasmid. The four nanoplexs were then applied in vitro for human normal hepacyte L02 and hepatoma HePG2 cell line, and in vivo for rabbits with hepatic VX2 tumor by injection of nanoplexs/lipiodol emulsion into the hepatic artery in a tumor target manner. The distribution, superficial potential, physical structure, morphology and chemical compositions of nanoplexs were evaluated by TEM, SEM, EDS etc., with the objective of understanding their roles in hepatoma TAE-gene therapy.ResultsIn vitro, L-nanoplex managed the highest gene transferring efficiency. Though with the second highest transfection activity, Pll-nanoplex showed the strongest tumor inhibition activity while maintaining safe to the normal hepacyte L02. In fact, only Pll-nanoplex can combine both the antitumoral effect to HePG2 and safe procedure to L02 among the four systems above. In vivo, being the only one with successful gene transference to hepatic VX2 tumor, Pll-nanoplex/lipiodol emulsion can target the tumor more specifically, which may explain its best therapeutic effect and hepatic biologic response. Further physical characterizations of the four nanoplexs suggested particle size and proper electronic organic surface may be crucial for nano-TAE gene therapy.ConclusionPll-nanoplex is the most proper system for the combined therapy due to its selectively retention in liver cancer cells, secondary to its morphological and physico-chemical properties of nanometric particle size, steady emulsion, proper organic and electronic surface.

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Multifunctional nanoplatforms application in the transcatheter chemoembolization against hepatocellular carcinoma

et al. 2023

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Hepatocellular carcinoma (HCC) has the sixth-highest new incidence and fourth-highest mortality worldwide. Transarterial chemoembolization (TACE) is one of the primary treatment strategies for unresectable HCC. However, the therapeutic effect is still unsatisfactory due to the insufficient distribution of antineoplastic drugs in tumor tissues and the worsened post-embolization tumor microenvironment (TME, e.g., hypoxia and reduced pH). Recently, using nanomaterials as a drug delivery platform for TACE therapy of HCC has been a research hotspot. With the development of nanotechnology, multifunctional nanoplatforms have been developed to embolize the tumor vasculature, creating conditions for improving the distribution and bioavailability of drugs in tumor tissues. Currently, the researchers are focusing on functionalizing nanomaterials to achieve high drug loading efficacy, thorough vascular embolization, tumor targeting, controlled sustained release of drugs, and real-time imaging in the TACE process to facilitate precise embolization and enable therapeutic procedures follow-up imaging of tumor lesions. Herein, we summarized the recent advances and applications of functionalized nanomaterials based on TACE against HCC, believing that developing these functionalized nanoplatforms may be a promising approach for improving the TACE therapeutic effect of HCC.

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The cooperative effect of p53 and Rb in local nanotherapy in a rabbit VX2 model of hepatocellular carcinoma

Cited by 5 publications

References 43 publications

<p>Transcatheter Intra-Arterial Infusion Combined with Interventional Photothermal Therapy for the Treatment of Hepatocellular Carcinoma</p>

<p>Transcatheter Intra-Arterial Infusion Combined with Interventional Photothermal Therapy for the Treatment of Hepatocellular Carcinoma</p>

Synergism of wt-p53 and synthetic material in local nano-TAE gene therapy of hepatoma: comparison of four systems and the possible mechanism

Multifunctional nanoplatforms application in the transcatheter chemoembolization against hepatocellular carcinoma

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