Journal
ADVANCED HEALTHCARE MATERIALS
Volume 5, Issue 19, Pages 2517-2527Publisher
WILEY
DOI: 10.1002/adhm.201600345
Keywords
-
Funding
- Major Scientific Research Project of National Nanotechnology Research (973) [2014CB931900]
- National Natural Science Foundation of China [21104065, 21274125, 21574118]
- Zhejiang Provincial Natural Science Foundation for Distinguished Young Scientists [LR16H160002]
- Scientific Research Foundation for Outstanding Young Scholars of Zhejiang Provincial People's Hospital [ZRA2015A012]
Ask authors/readers for more resources
Doxorubicin (DOX) is a widely used chemotherapeutic drug to treat a range of cancers. However, its unfavorable effects, particularly the cardiotoxicity and the induction of multidrug resistance (MDR), signifi cantly limit its clinical applications. Herein, a novel doxorubicin prodrug, PEG(2K)-DOX, is synthesized by conjugating a deprotonated doxorubicin molecule with the polyethylene glycol (PEG, MW: 2K) chain via pH-responsive hydrazone bond, and its potential as a better alternative than doxorubicin is evaluated. The data show that the amphiphilic PEG(2K)-DOX can self-assemble into stable nanoparticles with a high and fixed doxorubicin loading content (approximate to 20 wt%), a favorable size of 91.5 nm with a narrow polydispersity (PDI = 0.14), good stability, and pH-dependent release behavior due to the acid-cleavable linkage between PEG and doxorubicin. Although doxorubicin hardly accumulates in MDR cells, PEG(2K)-DOX nanoparticles signifi cantly increase the cellular uptake and cell-killing activity of doxorubicin in two MDR cancer cell lines MCF-7/ADR and KBv200, with the IC50 values dropped to 1.130% and 42.467% of doxorubicin, respectively. More impressively, PEG(2K)-DOX nanoparticles exhibit signifi cantly improved plasma pharmacokinetics, increased in vivo therapeutic efficacy against MDR xenograft tumors, and better in vivo safety compared with doxorubicin. PEG(2K)-DOX nanoparticles hold the promise to become a better alternative than doxorubicin for cancer treatment, especially for MDR tumors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available