Journal
MOLECULAR PHARMACEUTICS
Volume 14, Issue 9, Pages 3152-3163Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.7b00377
Keywords
PEGylation; ternary nanoparticles; sheddable shell; CD44 positive melanoma; microRNA-34a release
Funding
- National Natural Science Foundation of China [81422044]
Ask authors/readers for more resources
PEGylation can stabilize drug delivery systems for cancer therapy by creating repulsive interactions with biological components in vivo. While these interactions reduce nonspecific adsorption of drug-loaded particles onto nontarget surfaces, they also inhibit internalization of particles into target cells. To circumvent this so-called PEG-dilemma, we have developed nanoparticles with a PEG coating that is shed after arrival in target tissue. Positively charged polycation nano particles were assembled with microRNA-34a via electrostatic interactions and then coated again via electrostatic interactions with an anionic PEG derivative that separates from the nanoparticle in the acidic tumor microenvironment. The resulting ternary nanoparticles with a sheddable shell have nearly neutral surface charge, which markedly reduces nonspecific adsorption. Shedding the PEG coat enhanced nanoparticle uptake into CD44-positive melanoma cells and promoted microRNA-34a release, which down-regulated CD44 expression and thereby inhibited tumor growth. We conclude that nanocarriers with a sheddable shell show promise for cancer therapy.
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