Exploratory use of docetaxel loaded acid-prepared mesoporous spheres for the treatment of malignant melanoma

Cancer Nanotechnology

Research

Christopher C Landry¹  Maximilian B MacPherson²  Page Spiess²  Albert van der Vliet²  Arti Shukla²  Sameer Kaiser³  Ted A James⁴  Albert Emery⁵ 

[1] Department of Chemistry, University of Vermont, Burlington, VT, USA;Department of Pathology, University of Vermont, Burlington, VT, USA;Department of Surgery, Danbury Hospital, Danbury, CT, USA;Division of Surgical Oncology, Department of Surgery, University of Vermont, 89 Beaumont Ave, 05405, Burlington, VT, USA;University of Vermont College of Medicine, Burlington, VT, USA;

关键词: Melanoma;    Mesoporous;    Silica;    Microsphere;    Nanoparticle;    Docetaxel;   

DOI  :  10.1186/s12645-015-0009-y

 received in 2014-05-02, accepted in 2015-01-05,  发布年份 2015

来源: Springer

【 摘 要 】

IntroductionFive year survival for metastatic melanoma (MM) is very low at <10%. Therapeutic options have been limited secondary to systemic toxicity. As a result there has been a growing movement towards developing targeted drug delivery models. Prior research of this group has demonstrated the effectiveness of acid-prepared mesoporous spheres (APMS-TEG) in delivering chemotherapeutic agents at a lower effective dose than systemic administration. This study aims to assess the ability of the previously developed APMS-TEG particles to deliver therapeutic doses of docetaxel for the treatment of melanoma.MethodsIn vitro experiments were performed to assess docetaxel loading onto APMS-TEG particles and release kinetics. Toxicity experiments were performed using docetaxel and docetaxel loaded APMS-TEG. The effect on cell growth was assessed using the MelJuSo, UACC903, and WM1205 melanoma cell lines.ResultsDocetaxel demonstrated statistically significant dose dependent reduction in growth of melanoma cells. In all three cell lines, doses of 1 nM were sufficient to produce statistically significant reduction in cell growth. Scanning electron micrographs demonstrate increased uptake of APMS-TEG particles by melanoma cells in the first 24 hours, with the majority within the first 4 hours. Unloaded APMS particles had no effect on the melanoma cells, demonstrating that the particles themselves are not toxic. APMS-TEG particles had a peak release of drug within the first hour, with equilibration thereafter. The 5, 10, and 20 nM loaded particles all had statistically significant reduction in cell growth than the control groups.DiscussionThe high potency against melanoma cells makes docetaxel a suitable choice for loading into APMS-TEG particles. Docetaxel loaded APMS-TEG particles demonstrate significant activity against malignant melanoma and thus offer an innovative approach to the treatment of metastatic melanoma.

【 授权许可】

Unknown   
© Kaiser et al.; licensee Springer. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.