TY - JOUR
T1 - Rod-like cellulose nanocrystal/cis-aconityl-doxorubicin prodrug
T2 - A fluorescence-visible drug delivery system with enhanced cellular uptake and intracellular drug controlled release
AU - Li, Na
AU - Lu, Wei
AU - Yu, Jiahui
AU - Xiao, Yi
AU - Liu, Shiyuan
AU - Gan, Lin
AU - Huang, Jin
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Rod-like nanomedicines facilitate cellular uptake. This research is aimed to develop fluorescence-visible rod-like nanomedicines with enhanced cellular uptake and intracellular drug controlled release based on cis-aconityl-doxorubicin (CAD) labeled cellulose nanocrystal rods (CNR). Particularly, CAD was synthesized by the ring-opening reaction between cis-aconitic anhydride (CAA) and the amino group of Doxorubicin (DOX). Amidation reaction occurred between the 6-carboxylic groups of CAD and the amino groups of aminated CNR to give CAD labeled CNR (CAD@CNR). Compared with CNR, CAD@CNR showed similar morphology and crystal structure. The mean length of CAD@CNR was ca. 118 nm with aspect ratio ranging from 12 to 15, facilitating their endocytosis. CAD@CNR prodrug was rather stable in pH 7.4 phosphate buffer solution but tended to be hydrolyzed to release DOX under acidic condition, due to the rapid degradation of amide bonds between DOX and cis-aconitic acid via an intramolecular acid-catalyzed mechanism. CAD@CNR prodrug showed sustained drug release profiles over 40 h, and the cumulative drug release showed a tendency to increase from 36 to 80% with the pH value decreasing from 7.4 to 5.0. The half maximal inhibitory concentration (IC50) of CAD@CNR prodrug against NCI H 460 cells without NH4Cl (lysosomotropic weak bases) pretreatment was 1.75 times higher than that with 40 mM NH4Cl pretreatment, further confirmed that the DOX release from the CAD@CNR prodrug was triggered by the low pH value of lysosome (pH 5.0). Compared with DOX·HCl, CAD@CNR prodrug showed enhanced cellular uptake ability during 12 or 24 h of incubation due to the endocytosis mechanism of CAD@CNR prodrug. After incubation with cells, CAD@CNR prodrug could be observed by using fluorescence microscope due to the red fluorescence of DOX. In a word, CAD@CNR showed great potential as fluorescence-visible drug delivery system with enhanced cellular uptake and intracellular drug release due to its rod-like morphology, suitable aspect ratio, and acid-triggered drug release.
AB - Rod-like nanomedicines facilitate cellular uptake. This research is aimed to develop fluorescence-visible rod-like nanomedicines with enhanced cellular uptake and intracellular drug controlled release based on cis-aconityl-doxorubicin (CAD) labeled cellulose nanocrystal rods (CNR). Particularly, CAD was synthesized by the ring-opening reaction between cis-aconitic anhydride (CAA) and the amino group of Doxorubicin (DOX). Amidation reaction occurred between the 6-carboxylic groups of CAD and the amino groups of aminated CNR to give CAD labeled CNR (CAD@CNR). Compared with CNR, CAD@CNR showed similar morphology and crystal structure. The mean length of CAD@CNR was ca. 118 nm with aspect ratio ranging from 12 to 15, facilitating their endocytosis. CAD@CNR prodrug was rather stable in pH 7.4 phosphate buffer solution but tended to be hydrolyzed to release DOX under acidic condition, due to the rapid degradation of amide bonds between DOX and cis-aconitic acid via an intramolecular acid-catalyzed mechanism. CAD@CNR prodrug showed sustained drug release profiles over 40 h, and the cumulative drug release showed a tendency to increase from 36 to 80% with the pH value decreasing from 7.4 to 5.0. The half maximal inhibitory concentration (IC50) of CAD@CNR prodrug against NCI H 460 cells without NH4Cl (lysosomotropic weak bases) pretreatment was 1.75 times higher than that with 40 mM NH4Cl pretreatment, further confirmed that the DOX release from the CAD@CNR prodrug was triggered by the low pH value of lysosome (pH 5.0). Compared with DOX·HCl, CAD@CNR prodrug showed enhanced cellular uptake ability during 12 or 24 h of incubation due to the endocytosis mechanism of CAD@CNR prodrug. After incubation with cells, CAD@CNR prodrug could be observed by using fluorescence microscope due to the red fluorescence of DOX. In a word, CAD@CNR showed great potential as fluorescence-visible drug delivery system with enhanced cellular uptake and intracellular drug release due to its rod-like morphology, suitable aspect ratio, and acid-triggered drug release.
KW - CNR
KW - DOX prodrug
KW - Enhanced cellular uptake
KW - Fluorescence-visible
KW - Intracellular drug controlled release
UR - https://www.scopus.com/pages/publications/85047055341
U2 - 10.1016/j.msec.2018.04.099
DO - 10.1016/j.msec.2018.04.099
M3 - 文章
C2 - 30033244
AN - SCOPUS:85047055341
SN - 0928-4931
VL - 91
SP - 179
EP - 189
JO - Materials Science and Engineering C
JF - Materials Science and Engineering C
ER -