Detection of hepatocellular carcinoma in transgenic mice by Gd-DTPA- and rhodamine 123-conjugated human serum albumin nanoparticles in T1 magnetic resonance imaging

Watcharin, Waralee; Schmithals, Christian; Pleli, Thomas; Köberle, Verena; Korkusuz, H.; Hübner, Frank; Waidmann, Oliver; Zeuzem, Stefan; Korf, Horst‐Werner; Terfort, Andreas; Gelperina, Svetlana; Vogl, Thomas J.; Kreuter, Jörg; Piiper, Albrecht

doi:10.1016/j.jconrel.2014.11.023

Cited by 29 publications

(21 citation statements)

References 27 publications

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“…After weaning, the mice received ZnCl 2 (via the drinking water) to induce the expression of TGFa and thereby accelerate hepatocarcinogenesis. To detect and monitor the endogenously formed HCCs in the TGFa/c-myc mice, gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI was performed on a 3T MRI scanner (Siemens Magnetom Trio, Siemens Medical Solutions) as described recently (17)(18)(19). A representative image of HCC imaging by Gd-EOB-DTPA-enhanced MRI is shown in Supplementary Fig.…”

Section: Generation Of Transgenic Mice and Visualization Of Hccmentioning

confidence: 99%

“…The mice were anesthetized by intraperitoneal injection of ketamine (70mg/kg body weight) and xylazine (10 mg/kg body weight), followed by a basal T1-weighted MRI and immediately thereafter a Gd-DTPA-enhanced MRI (17). Twelve to 24 hours later, either iRGD or RGD control peptide (100 mL each via tail vein) was injected, followed by a basal and a Gd-DTPA-enhanced MRI (18). For quantitative analyses of the MRI data, signal intensities were measured with operator-defined regions of interest (ROI) drawn into the images as described recently (19).…”

Section: Gd-dtpa-enhanced Mri With and Without Irgdmentioning

confidence: 99%

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Improving Drug Penetrability with iRGD Leverages the Therapeutic Response to Sorafenib and Doxorubicin in Hepatocellular Carcinoma

et al. 2015

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AbstractiRGD is a derivative of the integrin-binding peptide RGD, which selectively increases the penetrability of tumor tissue to various coadministered substances in several preclinical models. In this study, we investigated the ability of iRGD to improve the delivery of sorafenib and doxorubicin therapy in hepatocellular carcinoma (HCC) using established mouse models of the disease. A contrast-enhanced MRI method was developed in parallel to assess the in vivo effects of iRGD in this setting. We found that iRGD improved the delivery of marker substances to the tumors of HCC-bearing mice about three-fold without a parallel increase in normal tissues. Control peptides lacking the critical CendR motif had no effect. Similarly, iRGD also selectively increased the signal intensity from tumors in Gd-DTPAenhanced MRI. In terms of antitumor efficacy, iRGD coadministration significantly augmented the individual inhibitory effects of sorafenib and doxorubicin without increasing systemic toxicity. Overall, our results offered a preclinical proof of concept for the use of iRGD coadministration as a strategy to widen the therapeutic window for HCC chemotherapy, as monitored by Gd-DTPA-enhanced MRI as a noninvasive, clinically applicable method to identify iRGD-reactive tumors.Cancer Res; 75(15); 3147-54. Ó2015 AACR.

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Section: Generation Of Transgenic Mice and Visualization Of Hccmentioning

confidence: 99%

Section: Gd-dtpa-enhanced Mri With and Without Irgdmentioning

confidence: 99%

Improving Drug Penetrability with iRGD Leverages the Therapeutic Response to Sorafenib and Doxorubicin in Hepatocellular Carcinoma

et al. 2015

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“…To investigate if M2pep shows selectivity for TAMs in HCC, we used resected HCCs formed endogenously in TGFα/c-myc transgenic mice as well as HepG2 xenografts excised from nude mice [ 21 – 23 ]. The resected tumors were dissociated and the suspended cells were incubated with fluorescently labeled M2pep for 30 min on ice.…”

Section: Resultsmentioning

confidence: 99%

“…The animals were inspected once per week. Approximately 20–24 weeks after induction, HCCs were detected by contrast-enhanced magnetic resonance imaging as described recently [ 22 , 23 ]. Mice with visualized HCCs of a diameter of 0.5 to 0.8 cm were sacrificed, the tumors excised and used immediately for the generation of single cell suspensions.…”

Section: Methodsmentioning

confidence: 99%

Selective targeting of tumor associated macrophages in different tumor models

et al. 2018

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Tumor progression largely depends on the presence of alternatively polarized (M2) tumor-associated macrophages (TAMs), whereas the classical M1-polarized macrophages can promote anti-tumorigenic immune responses. Thus, selective inhibition of M2-TAMs is a desirable anti-cancer approach in highly resistant tumor entities such as hepatocellular carcinoma (HCC) or breast cancer. We here examined whether a peptide that selectively binds to and is internalized by in vitro-differentiated murine M2 macrophages as compared to M1 macrophages, termed M2pep, could be used to selectively target TAMs in HCC and breast carcinoma. We confirmed selectivity of M2pep for in vitro M2 polarized macrophages. Upon incubation of suspended mixed 4T1 tumor cells with M2pep, high amounts of the TAMs were found to be associated with M2pep, whereas in mixed tumor cell suspensions from two HCC mouse models, M2pep showed only low-degree binding to TAMs. M2pep also showed low-degree targeting of liver macrophages. This indicates that the TAMs in different tumor entities show different targeting of M2pep and that M2pep is a very promising approach to develop selective M2-TAM-targeting in tumor entities containing M2-TAMs with significant amounts of the so far elusive M2pep receptor(s).

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“…In Vivo MRI Detection : Gd 3+ nanomaterials have been widely used as T 1 contrast agent . MRI of PATP nanoparticles incubated in saline at different concentration of Gd 3+ , rating of 0.023, 0.046, 0.092, 0.180, and 0.370 × 10 −3 m .…”

Section: Methodsmentioning

confidence: 99%

Drug‐Controlled Release Based on Complementary Base Pairing Rules for Photodynamic–Photothermal Synergistic Tumor Treatment

Zhan

Shi

Zhou

et al. 2018

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studies devoted to exploration drug controlled release system using such complementary base pairing rules.In this manuscript, a bioinspired temperature response controlled drug release nanosystem based on complementary base pairing rules were designed and prepared (Scheme 1). Just as mentioned above, adenine can form base pairs with thymine through specific A = T hydrogen bond, which fracture under high temperature conditions. Therefore, an adenine modified polydopamine nanoparticle (A-PDA, a photothermal nanoparticle for photothermal therapy (PTT) can be triggered by 808 nm light) and a thymine modified Zinc phthalocyanine (T-ZnPc, an efficient photosensitizer for photodynamic therapy (PDT) can be excited by 665 nm light) were designed and prepared. T-ZnPc can easily assemble on the surface of A-PDA driving for complementary base pairing rules between A and T. Furthermore, Gd 3+ was modified on the surface of above assembled nanoparticles upon simple mixing because Gd 3+ can easily chelate with catechol groups of PDA. [11,12] After assembled on A-PDA nanoparticles surface, the PDT activity was sharply decreased, which could ensure its safety during delivery process. It's well known that polydopamine can absorb near infrared (NIR) irradiation (700-900 nm) to converse thermal with high efficiency. [13][14][15][16] Hence, after being trapped by tumor cells and irradiated by 808 nm light, the photothermal efficacy of A-PDA nanoparticles can not only trigger T-ZnPc release and activation but also provide the PTT induced cell death to synergistic PDT anticancer process of T-ZnPc after 665 nm irradiation. In addition, Gd 3+ in the system can provide magnetic resonance imaging (MRI)-guided delivery and theranostic function. [17,18] Results and Discussion Synthesis and Characterization of the A-PDA NanoparticlesAccording to a published literature, dopamine hydrochloride (DA) can self-polymerize under alkaline conditions (deionized water/isopropanol = 8:1, v/v) in the present of oxygen at room temperature. [19] Isopropanol was employed to control the polymerization process of dopamine to obtain PDA nanoparticles since its hindrance effect. PDA nanoparticles can be stable dispersed in water. The formation of PDA nanoparticles Controlled drug release systems can enhance the safety and availability but avoid the side effect of drugs. Herein, the concept of DNA complementary base pairing rules in biology is used to design and prepare a photothermaltriggered drug release system. Adenine (A) modified polydopamine nanoparticles (A-PDA, photothermal reagent) can effectively bind with thymine (T) modified Zinc phthalocyanine (T-ZnPc, photosensitizer) forming A-PDA = T-ZnPc (PATP) complex based on A = T complementary base pairing rules. Similar to DNA, whose base pairing in double strands will break by heating, T-ZnPc can be effectively released from A-PDA after near infrared irradiation-triggered light-thermal conversion to obtain satisfactory photodynamic-photothermal synergistic tumor treatment. In addition, PDA can carry abund...

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Detection of hepatocellular carcinoma in transgenic mice by Gd-DTPA- and rhodamine 123-conjugated human serum albumin nanoparticles in T1 magnetic resonance imaging

Cited by 29 publications

References 27 publications

Improving Drug Penetrability with iRGD Leverages the Therapeutic Response to Sorafenib and Doxorubicin in Hepatocellular Carcinoma

Improving Drug Penetrability with iRGD Leverages the Therapeutic Response to Sorafenib and Doxorubicin in Hepatocellular Carcinoma

Selective targeting of tumor associated macrophages in different tumor models

Drug‐Controlled Release Based on Complementary Base Pairing Rules for Photodynamic–Photothermal Synergistic Tumor Treatment

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