Limits...
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

Body weight alternation following the injection of Gd-DTPA/DACHPt-loaded micelles, oxaliplatin, and saline.Notes: The injection of oxaliplatin caused the most severe weight loss among groups.Abbreviations: DACHPt, (1,2-diaminocyclohexane)platinum(II); Gd-DTPA, gadolinium-diethylenetriaminpentaacetic acid.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4487238&req=5

f8-ijn-10-4137: Body weight alternation following the injection of Gd-DTPA/DACHPt-loaded micelles, oxaliplatin, and saline.Notes: The injection of oxaliplatin caused the most severe weight loss among groups.Abbreviations: DACHPt, (1,2-diaminocyclohexane)platinum(II); Gd-DTPA, gadolinium-diethylenetriaminpentaacetic acid.

Mentions: Following treatment with Gd-DTPA/DACHPt-loaded micelles, oxaliplatin, or saline, all rats survived to the end stage of cancer disease. No abnormal presentation was encountered during these treatments, with the exception of weight loss, which is summarized in Figure 8. The mean body weight of oxaliplatin-treated rats decreased by 14% and 22% by day 3 and day 7, respectively, versus 10% and 13% in the micelle-treated rats. Systemic toxicity was evaluated by blood testing. Alanine aminotransferase levels increased after injection with the micelles and oxaliplatin, more so with oxaliplatin (Figure 9A). The alanine aminotransferase values from liver tissues for oxaliplatin injection may be even higher than those for micelle injection as micelles induced much higher rates of tumor cell death compared with oxaliplatin. Moreover, the Gd-DTPA/DACHPt-loaded micelle-treated rats exhibited a decrease in blood albumin levels at days 1 and 7 and an increase at day 14 (Figure 9B). In contrast, the oxaliplatin-treated rats exhibited severe decreases in blood albumin levels until day 14. Thus, micelle injection caused a reversible hepatic dysfunction, while oxaliplatin caused a more severe and progressive disorder. Total bilirubin levels and renal function were not affected by either treatment (Figure 9C and D).


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)

Body weight alternation following the injection of Gd-DTPA/DACHPt-loaded micelles, oxaliplatin, and saline.Notes: The injection of oxaliplatin caused the most severe weight loss among groups.Abbreviations: DACHPt, (1,2-diaminocyclohexane)platinum(II); Gd-DTPA, gadolinium-diethylenetriaminpentaacetic acid.
© Copyright Policy
Related In: Results  -  Collection

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

f8-ijn-10-4137: Body weight alternation following the injection of Gd-DTPA/DACHPt-loaded micelles, oxaliplatin, and saline.Notes: The injection of oxaliplatin caused the most severe weight loss among groups.Abbreviations: DACHPt, (1,2-diaminocyclohexane)platinum(II); Gd-DTPA, gadolinium-diethylenetriaminpentaacetic acid.
Mentions: Following treatment with Gd-DTPA/DACHPt-loaded micelles, oxaliplatin, or saline, all rats survived to the end stage of cancer disease. No abnormal presentation was encountered during these treatments, with the exception of weight loss, which is summarized in Figure 8. The mean body weight of oxaliplatin-treated rats decreased by 14% and 22% by day 3 and day 7, respectively, versus 10% and 13% in the micelle-treated rats. Systemic toxicity was evaluated by blood testing. Alanine aminotransferase levels increased after injection with the micelles and oxaliplatin, more so with oxaliplatin (Figure 9A). The alanine aminotransferase values from liver tissues for oxaliplatin injection may be even higher than those for micelle injection as micelles induced much higher rates of tumor cell death compared with oxaliplatin. Moreover, the Gd-DTPA/DACHPt-loaded micelle-treated rats exhibited a decrease in blood albumin levels at days 1 and 7 and an increase at day 14 (Figure 9B). In contrast, the oxaliplatin-treated rats exhibited severe decreases in blood albumin levels until day 14. Thus, micelle injection caused a reversible hepatic dysfunction, while oxaliplatin caused a more severe and progressive disorder. Total bilirubin levels and renal function were not affected by either treatment (Figure 9C and D).

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