Local application of doxorubicin- loaded Iron oxid nanoparticles and the vascular disrupting agent via the hepatic artery: chemoembolization–photothermal ablation treatment of hepatocellular carcinoma in rats

Abstract

ObjectivesThis study investigates the effectiveness of local application of doxorubicin(Dox)-loaded, polydopamine (PDA)- coated single crystal hematite (α- Fe2O3) nanocubes (Fe2O3-PDA-Dox) and combretastatin A-4 phosphate disodium(CA4P)in treating hepatocellular carcinoma (HCC) in rats.MethodsThe magnetic characteristics and photothermal effects of the nanoparticles were determined in vitro. Tumor-bearing Sprague–Dawley rats were divided into 3 groups of 8 according to treatment: controls, transarterial chemoembolization–photothermal ablation (pTACE) (Lipidol+Fe2O3-PDA-Dox + NIR), and CA4P + pTACE (CA4P+ Lipidol+Fe2O3-PDA-Dox + NIR). Drugs were administered through the hepatic artery, and the tumors exposed to 808-nm near-infrared radiation. The Fe content of tumors was assessed using neutron activation analysis. Treatment effectiveness was assessed using heating curves, magnetic resonance imaging, pathology results, and immunohistochemical analysis.ResultsThe mean tumor Fe content was greater in rats treated with CA4P + pTACE (1 h, 23.72 ± 12.45 μg/g; 24 h, 14.61 ± 8.23 μg/g) than in those treated with pTACE alone (1 h, 5.66 ± 4.29 μg/g; 24 h, 2.76 ± 1.33 μg/g). The tumor T2 imaging signal was lower in rats treated with CA4P + pTACE. Following laser irradiation, the tumor temperature increased, with higher temperatures reached in the CA4P + pTACE group (62 °C vs 55 °C). Tumor cells exhibited necrosis, apoptosis, and proliferation inhibition, with greater effects in the CA4P + pTACE group. Transient liver and kidney toxicity were observed on day 3, with more severe effects after CA4P + pTACE.ConclusionsFe2O3-PDA-Dox nanoparticles are effective for TACE–PTA. Pretreatment with CA4P increases nanoparticle uptake by tumors, increasing the treatment effectiveness without increasing hepatorenal toxicity.

Nanomaterial-Based Antivascular Therapy in the Multimodal Treatment of Cancer

“…Yuan designed a nanocube (Fe 2 O 3 -PDA-Dox) that they combined with CA4P to treat HCC. CA4P increased the permeability of tumor blood vessels and enhanced the effects of TACE combined with photothermal ablation (pTACE) [153].…”

Multifunctional nanoplatforms application in the transcatheter chemoembolization against hepatocellular carcinoma

“…As shown in Table 4 , animal models (such as rats, rabbits, or swine) are still the main research subjects of nanoplatforms for the diagnosis and treatment of liver cancer. As one of the most used animal models, rats are cheap in price, easy to obtain, and relatively easy to model, so they are widely used in studying nanoplatform imaging diagnosis, drug delivery, and PTT [ 52 , 56 , 61 , 98 ]. Whereas, due to the requirements of vascular size for interventional intubation, the study of rat liver cancer models for TACE is relatively rare.…”

Pictorial Imaging-Histopathology Correlation in a Rabbit with Hepatic VX2 Tumor Treated by Transarterial Vascular Disrupting Agent Administration

“…Despite favorable safety and efficacy with systemic OncoCiDia, currently we are elaborating locoregional OncoCiDia through interventional transcatheter arterial drug deliveries for certain indications, thus to substantially reduce the amount of the two applied agents but meanwhile to make OncoCiDia even safer and more efficacious. To our knowledge, intra-arterially delivered VDA was reported only in combinatory manner for experimental therapy of liver malignancies [14]. The anticancer competence of a VDA given by arterial catheter for liver cancers has never been evaluated or reported, most likely due to the influence from the previously documented unfavorable result in rats with renal tumor allograft [15].…”