Five-Part Pentameric Nanocomplex Shows Improved Efficacy
of Doxorubicin in CD44+ Cancer Cells
Posted on 2017-11-09 - 09:15
The
CD44 receptor is common among
many cancer types where overexpression is synonymous with poor prognosis
in prostate, glioma, and breast cancer. More notably CD44 overexpression
has been shown in a number of different cancer stem cells (CSC) which
are present in many solid tumors and drive growth, recurrence, and
resistance to conventional therapies. Triple negative breast cancer
CSCs correlate to worse prognosis and early relapse due to higher
drug resistance and increased tumor heterogeneity and thus are prime
targets for anticancer therapy. To specifically target cells overexpressing
CD44 receptors, including CSCs, we synthesized a pentameric nanocomplex
(PNC) containing gold nanoparticles, doxorubicin (Dox) conjugated
to thiolated hyaluronic acid via an acid-labile hydrazone bond, and
thiolated poly(ethylene glycol) DNA CD44 aptamer. In vitro drug release
was highest at 8 h time point at acidic pH (pH 4.7) and in 10 mM glutathione.
The PNC is almost an order of magnitude more effective than Dox alone
in CD44+ cells versus CD44 low cells. Functionally, the PNC reduced
CSC self-renewal. The PNC provides a therapeutic strategy that can
improve the efficiency of Dox and decrease nontargeted toxicity thereby
prolonging its use to individual patients.
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Beals, Nathan; Thiagarajan, Praveena S.; Soehnlen, Eric; Das, Arijit; Reizes, Ofer; D. Lathia, Justin; et al. (2017). Five-Part Pentameric Nanocomplex Shows Improved Efficacy
of Doxorubicin in CD44+ Cancer Cells. ACS Publications. Collection. https://doi.org/10.1021/acsomega.7b01168
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AUTHORS (7)
NB
Nathan Beals
PT
Praveena S. Thiagarajan
ES
Eric Soehnlen
AD
Arijit Das
OR
Ofer Reizes
JD
Justin D. Lathia
SB
Soumitra Basu
KEYWORDS
drive growthdrug releasepentameric nanocomplexCD 44 receptorbreast cancer CSCsanticancer therapycancer typesCSC self-renewalacid-labile hydrazone bondCD 44tumor heterogeneityFive-Part Pentameric Nanocomplex ShowsCD 44 overexpression10 mM glutathionetarget cells overexpressing CD 44 receptorsdrug resistancebreast cancerDNA CD 44 aptamer8 h time pointgold nanoparticlesdecrease nontargeted toxicityDoxacidic pHPNC