TY - JOUR
T1 - A dual-prodrug nanoparticle based on chitosan oligosaccharide for enhanced tumor-targeted drug delivery
AU - Chen, Xia
AU - Bremner, David H.
AU - Ye, Yuhan
AU - Lou, Jiadong
AU - Niu, Shiwei
AU - Zhu, Li-Min
PY - 2021/3/26
Y1 - 2021/3/26
N2 - The premature leakage of chemotherapeutics during delivery impedes drugs from entering tumor cells, which produces considerable side effects in normal organs. Herein, we describe a hydrophobic-hydrophilic balanced self-assembled prodrug nanoparticle (HA-DOX@HA-CSO-g-OA), formed via a facile synthesis based on chitosan oligosaccharide to reduce the non-targeting risk of premature leakage of chemotherapeutics during their delivery. The HA-DOX@HA-CSO-g-OA have a suitable size (~186 nm) with a doxorubicin (DOX) loading of 9.88% and an oleanolic acid (OA) loading efficiency of 27.34%. The release of DOX or OA is pH-dependent and responds particularly well to the acidic tumor microenvironment. In vitro antitumor activity studies revealed that HA-DOX@HA-CSO-g-OA had enhanced performance in promoting tumor apoptosis and displayed significant anticancer effects compared to mono-delivery. In vitro cell studies showed that HA-functionalized nanoparticles could enhance the cellular uptake in tumor cells. Therefore, HA-DOX@HA-CSO-g-OA is a promising vehicle for CD44-targeted co-delivery of cancer chemotherapy, which deserves further evaluation.
AB - The premature leakage of chemotherapeutics during delivery impedes drugs from entering tumor cells, which produces considerable side effects in normal organs. Herein, we describe a hydrophobic-hydrophilic balanced self-assembled prodrug nanoparticle (HA-DOX@HA-CSO-g-OA), formed via a facile synthesis based on chitosan oligosaccharide to reduce the non-targeting risk of premature leakage of chemotherapeutics during their delivery. The HA-DOX@HA-CSO-g-OA have a suitable size (~186 nm) with a doxorubicin (DOX) loading of 9.88% and an oleanolic acid (OA) loading efficiency of 27.34%. The release of DOX or OA is pH-dependent and responds particularly well to the acidic tumor microenvironment. In vitro antitumor activity studies revealed that HA-DOX@HA-CSO-g-OA had enhanced performance in promoting tumor apoptosis and displayed significant anticancer effects compared to mono-delivery. In vitro cell studies showed that HA-functionalized nanoparticles could enhance the cellular uptake in tumor cells. Therefore, HA-DOX@HA-CSO-g-OA is a promising vehicle for CD44-targeted co-delivery of cancer chemotherapy, which deserves further evaluation.
U2 - 10.1016/j.colsurfa.2021.126512
DO - 10.1016/j.colsurfa.2021.126512
M3 - Article
JO - Colloids and Surfaces A: Physicochemical and Engineering Aspects
JF - Colloids and Surfaces A: Physicochemical and Engineering Aspects
SN - 0927-7757
M1 - 126512
ER -