TY - JOUR
T1 - ssDNA nanotubes for selective targeting of glioblastoma and delivery of doxorubicin for enhanced survival
AU - Harris, Michael A.
AU - Kuang, Huihui
AU - Schneiderman, Zachary
AU - Shiao, Maple L.
AU - Crane, Andrew T.
AU - Chrostek, Matthew R.
AU - Tăbăran, Alexandru Flaviu
AU - Pengo, Thomas
AU - Liaw, Kevin
AU - Xu, Beibei
AU - Lin, Lucy
AU - Chen, Clark C.
AU - Gerard O'Sullivan, M.
AU - Kannan, Rangaramanujam M.
AU - Low, Walter C.
AU - Kokkoli, Efrosini
N1 - Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved;
PY - 2021/12
Y1 - 2021/12
N2 - Effective treatment of glioblastoma remains a daunting challenge. One of the major hurdles in the development of therapeutics is their inability to cross the blood-brain tumor barrier (BBTB). Local delivery is an alternative approach that can still suffer from toxicity in the absence of target selectivity. Here, we show that nanotubes formed from self-assembly of ssDNA-amphiphiles are stable in serum and nucleases. After bilateral brain injections, nanotubes show preferential retention by tumors compared to normal brain and are taken up by glioblastoma cells through scavenger receptor binding and macropinocytosis. After intravenous injection, they cross the BBTB and internalize in glioblastoma cells. In a minimal residual disease model, local delivery of doxorubicin showed signs of toxicity in the spleen and liver. In contrast, delivery of doxorubicin by the nanotubes resulted in no systemic toxicity and enhanced mouse survival. Our results demonstrate that ssDNA nanotubes are a promising drug delivery vehicle to glioblastoma.
AB - Effective treatment of glioblastoma remains a daunting challenge. One of the major hurdles in the development of therapeutics is their inability to cross the blood-brain tumor barrier (BBTB). Local delivery is an alternative approach that can still suffer from toxicity in the absence of target selectivity. Here, we show that nanotubes formed from self-assembly of ssDNA-amphiphiles are stable in serum and nucleases. After bilateral brain injections, nanotubes show preferential retention by tumors compared to normal brain and are taken up by glioblastoma cells through scavenger receptor binding and macropinocytosis. After intravenous injection, they cross the BBTB and internalize in glioblastoma cells. In a minimal residual disease model, local delivery of doxorubicin showed signs of toxicity in the spleen and liver. In contrast, delivery of doxorubicin by the nanotubes resulted in no systemic toxicity and enhanced mouse survival. Our results demonstrate that ssDNA nanotubes are a promising drug delivery vehicle to glioblastoma.
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U2 - 10.1126/sciadv.abl5872
DO - 10.1126/sciadv.abl5872
M3 - Article
C2 - 34851666
AN - SCOPUS:85120696903
SN - 2375-2548
VL - 7
JO - Science Advances
JF - Science Advances
IS - 49
M1 - eabl5872
ER -
