Multifunctional polymeric nanoplexes for anticancer co-delivery of p53 and Mitoxantrone
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Date
2014-09
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Publisher
Journal of Materials Chemistry B.
Abstract
Co-delivery of the anticancer drug, mitoxantrone (MTO) and the gene encoding tumor suppressor protein
p53 was evaluated towards anticancer combinatorial therapy. The nanoplatforms developed herein are
assembled by coupling b-cyclodextrin and the cationic polymer, polyethyleneimine to a hydrophilic
polymer, pullulan (PPEICD). The b-cyclodextrin serves as a nanocontainer for the drug MTO, while the
cationic moiety can condense pDNA. Acid base titrations provided insight into the buffering capacity of
the PPEICD conjugate. Cytotoxicity studies by MTT assay in HepG2 and C6 cell lines and
hemocompatibility studies confirmed the conjugate to be nontoxic and hemocompatible. In vitro release
studies of MTO in phosphate buffered saline pH 7.4 showed an initial burst effect followed by a slow
drug release. The released data fitted with the Korsmeyer–Peppas model and their diffusional exponents
suggest that the drug release from the polymeric system followed diffusion and non-Fickian transport.
Combined drug and gene loaded nanoplexes have a more apoptotic effect than either the drug or gene
individually as confirmed by MTT assay and live dead assay. This indicated the significance of the
combined drug and gene delivery system and the ability of the nanoplatform to overcome the multidrug
resistance (MDR) of MTO. Moreover, preference of asialoglycoprotein receptor (ASGPR) mediated
internalization for nanoparticle cellular uptake in HepG2 cell lines was identified by treating with the
inhibitor asialofetuin. Cell studies in both HepG2 and C6 cell lines demonstrated that the nanoplatform
PPEICD can efficiently and selectively deliver both p53 and MTO to cancer cells inducing high cell death.
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Citation
Journal of Materials Chemistry B. 2014;2:8005-16.