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MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model.

Vinh NQ, Naka S, Cabral H, Murayama H, Kaida S, Kataoka K, Morikawa S, Tani T - Int J Nanomedicine (2015)

Bottom Line: The development of tumor-targeting systems may improve treatment outcomes.Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or saline controls.Our results suggest that Gd-DTPA/DACHPt-loaded micelles are a promising approach for effective diagnosis and treatment of advanced HCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Shiga University of Medical Science, Shiga, Japan.

ABSTRACT
Hepatocellular carcinoma (HCC) is one of the most intractable and lethal cancers; most cases are diagnosed at advanced stages with underlying liver dysfunction and are frequently resistant to conventional chemotherapy and radiotherapy. The development of tumor-targeting systems may improve treatment outcomes. Nanomedicine platforms are of particular interest for enhancing chemotherapeutic efficiency, and they include polymeric micelles, which enable targeting of multiple drugs to solid tumors, including imaging and therapeutic agents. This allows concurrent diagnosis, targeting strategy validation, and efficacy assessment. We used polymeric micelles containing the T1-weighted magnetic resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA) and the parent complex of the anticancer drug oxaliplatin [(1,2-diaminocyclohexane)platinum(II) (DACHPt)] for simultaneous imaging and therapy in an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected into the hepatic artery, and magnetic resonance imaging performance and antitumor activity against HCC, as well as adverse drug reactions were assessed. After a single administration, the micelles achieved strong and specific tumor contrast enhancement, induced high levels of tumor apoptosis, and significantly suppressed tumor size and growth. Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or saline controls. Our results suggest that Gd-DTPA/DACHPt-loaded micelles are a promising approach for effective diagnosis and treatment of advanced HCC.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of self-assembly of Gd-DTPA/DACHPt-loaded micelles.Notes: MRI-detectable polymeric micelles for simultaneous diagnosis and therapy are created by incorporating the T1-weighted MRI contrast agent Gd-DTPA and the platinum anticancer drug DACHPt nitrate chloride, which is the parent complex of the anticancer drug oxaliplatin, within the micelle cores.
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f1-ijn-10-4137: Schematic diagram of self-assembly of Gd-DTPA/DACHPt-loaded micelles.Notes: MRI-detectable polymeric micelles for simultaneous diagnosis and therapy are created by incorporating the T1-weighted MRI contrast agent Gd-DTPA and the platinum anticancer drug DACHPt nitrate chloride, which is the parent complex of the anticancer drug oxaliplatin, within the micelle cores.

Mentions: We recently developed MRI-detectable polymeric micelles for simultaneous diagnosis and therapy by incorporating the T1-weighted MRI contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA) and the platinum anticancer drug DACHPt, the parent complex of the anticancer drug oxaliplatin, within the cores of micelles (Figure 1). Earlier characterization of these micelles revealed a relatively small diameter of 33 nm, which allowed high penetration and accumulation even in tumors with poor permeability.17,30 In this study, we examined the feasibility of using these Gd-DTPA/DACHPt-loaded micelles to simultaneously diagnose and treat a clinically relevant rat model of HCC that was generated using the N1-S1 hepatoma cell line, which exhibits high levels of malignancy and hypervascularization. After injecting the micelles through the hepatic artery, we performed MRI, tumor cytotoxicity, biochemistry, and tumor progression analyses to investigate MRI performance, adverse reactions, and antitumor activity of the micelles. Our results demonstrated the safety and enhanced efficacy of Gd-DTPA/DACHPt-loaded micelles for the selective imaging and treatment of HCC.


MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model.

Vinh NQ, Naka S, Cabral H, Murayama H, Kaida S, Kataoka K, Morikawa S, Tani T - Int J Nanomedicine (2015)

Schematic diagram of self-assembly of Gd-DTPA/DACHPt-loaded micelles.Notes: MRI-detectable polymeric micelles for simultaneous diagnosis and therapy are created by incorporating the T1-weighted MRI contrast agent Gd-DTPA and the platinum anticancer drug DACHPt nitrate chloride, which is the parent complex of the anticancer drug oxaliplatin, within the micelle cores.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4487238&req=5

f1-ijn-10-4137: Schematic diagram of self-assembly of Gd-DTPA/DACHPt-loaded micelles.Notes: MRI-detectable polymeric micelles for simultaneous diagnosis and therapy are created by incorporating the T1-weighted MRI contrast agent Gd-DTPA and the platinum anticancer drug DACHPt nitrate chloride, which is the parent complex of the anticancer drug oxaliplatin, within the micelle cores.
Mentions: We recently developed MRI-detectable polymeric micelles for simultaneous diagnosis and therapy by incorporating the T1-weighted MRI contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA) and the platinum anticancer drug DACHPt, the parent complex of the anticancer drug oxaliplatin, within the cores of micelles (Figure 1). Earlier characterization of these micelles revealed a relatively small diameter of 33 nm, which allowed high penetration and accumulation even in tumors with poor permeability.17,30 In this study, we examined the feasibility of using these Gd-DTPA/DACHPt-loaded micelles to simultaneously diagnose and treat a clinically relevant rat model of HCC that was generated using the N1-S1 hepatoma cell line, which exhibits high levels of malignancy and hypervascularization. After injecting the micelles through the hepatic artery, we performed MRI, tumor cytotoxicity, biochemistry, and tumor progression analyses to investigate MRI performance, adverse reactions, and antitumor activity of the micelles. Our results demonstrated the safety and enhanced efficacy of Gd-DTPA/DACHPt-loaded micelles for the selective imaging and treatment of HCC.

Bottom Line: The development of tumor-targeting systems may improve treatment outcomes.Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or saline controls.Our results suggest that Gd-DTPA/DACHPt-loaded micelles are a promising approach for effective diagnosis and treatment of advanced HCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Shiga University of Medical Science, Shiga, Japan.

ABSTRACT
Hepatocellular carcinoma (HCC) is one of the most intractable and lethal cancers; most cases are diagnosed at advanced stages with underlying liver dysfunction and are frequently resistant to conventional chemotherapy and radiotherapy. The development of tumor-targeting systems may improve treatment outcomes. Nanomedicine platforms are of particular interest for enhancing chemotherapeutic efficiency, and they include polymeric micelles, which enable targeting of multiple drugs to solid tumors, including imaging and therapeutic agents. This allows concurrent diagnosis, targeting strategy validation, and efficacy assessment. We used polymeric micelles containing the T1-weighted magnetic resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA) and the parent complex of the anticancer drug oxaliplatin [(1,2-diaminocyclohexane)platinum(II) (DACHPt)] for simultaneous imaging and therapy in an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected into the hepatic artery, and magnetic resonance imaging performance and antitumor activity against HCC, as well as adverse drug reactions were assessed. After a single administration, the micelles achieved strong and specific tumor contrast enhancement, induced high levels of tumor apoptosis, and significantly suppressed tumor size and growth. Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or saline controls. Our results suggest that Gd-DTPA/DACHPt-loaded micelles are a promising approach for effective diagnosis and treatment of advanced HCC.

No MeSH data available.


Related in: MedlinePlus