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Author Salzano, Giuseppina ♦ Costa, Daniel F. ♦ Sarisozen, Can ♦ Luther, Ed ♦ Mattheolabakis, George ♦ Dhargalkar, Pooja P. ♦ Torchilin, Vladimir P.
Source World Health Organization (WHO)-Global Index Medicus
Content type Text
Publisher Wiley-VCH
File Format HTM / HTML
Language English
Difficulty Level Medium
Subject Domain (in DDC) Technology ♦ Medicine & health
Abstract Dual stimuli-sensitive mixed polymeric micelles (MM) are developed for co-delivery of the endogenous tumor suppressor miRNA-34a and the chemotherapeutic agent doxorubicin (Dox) into cancer cells. The novelty of the system resides in two stimuli-sensitive prodrugs, a matrix metalloproteinase 2 (MMP2)-sensitive Dox conjugate and a reducing agent (glutathione, GSH)-sensitive miRNA-34a conjugate, self-assembled in a single particle decorated with a polyethylene glycol corona for longevity, and a cell-penetrating peptide (TATp) for enhanced intracellular delivery. The MMP2-sensitivity of the system results in threefold higher cytotoxicity in MMP2-overexpressing HT1080 cells compared to low MMP2-expressing MCF7 cells. Cellular internalization of Dox increases by more than 70% after inclusion of TATp to the formulation. MMP2-sensitive MM also inhibits proliferation and migration of HT1080 cells. Moreover, GSH-sensitive MM allows for an efficient downregulation of Bcl2, survivin, and notch1 (65%, 55%, and 46%, respectively) in HT1080 cells. Combination of both conjugates in dual sensitive MM reduces HT1080 cell viability to 40% and expression of Bcl2 and survivin. Finally, 50% cell death is observed in 3D models of tumor mass. The results confirm the potential of the MM to codeliver miRNA-34a and doxorubicin triggered by dual stimuli inherent of tumor tissues.
Description Country affiliation: United States
Author Affiliation: Salzano G ( Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, 02115, USA.); Costa DF ( Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, 02115, USA.); Sarisozen C ( CAPES Foundation, Ministry of Education of Brazil, Brasília, DF, 70040-020, Brazil.); Luther E ( Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, 02115, USA.); Mattheolabakis G ( Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, 02115, USA.); Dhargalkar PP ( Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, 02115, USA.); Torchilin VP ( Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, 02115, USA.)
ISSN 16136810
Educational Role Student ♦ Teacher
Age Range above 22 year
Educational Use Reading ♦ Research ♦ Self Learning
Interactivity Type Expositive
Education Level UG and PG
Learning Resource Type Article
Publisher Date 2016-09-01
Publisher Place Germany
e-ISSN 16136829
Journal Small
Volume Number 12
Issue Number 35


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Source: WHO-Global Index Medicus