Co-delivery of doxorubicin and oleanolic acid by triple-sensitive nanocomposite based on chitosan for effective promoting tumor apoptosis

Xia Chen; Shiwei Niu; David H. Bremner; Xuejing Zhang; Hongmei Zhang; Yanyan Zhang; Shude Li; Li-Min Zhu

doi:10.1016/j.carbpol.2020.116672

Co-delivery of doxorubicin and oleanolic acid by triple-sensitive nanocomposite based on chitosan for effective promoting tumor apoptosis

Xia Chen, Shiwei Niu, David H. Bremner, Xuejing Zhang, Hongmei Zhang, Yanyan Zhang, Shude Li^*, Li-Min Zhu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article

Abstract

Nanocomposites as “stevedores” for co-delivery of multidrugs hold great promise in addressing the drawbacks of traditional cancer chemotherapy. In this work, our strategy presents a new avenue for the stepwise release of two co-delivered agents into the tumor cells. The hybrid nanocomposite consists of a pH-responsive chitosan (CS), a thermosensitive poly(N-vinylcaprolactam) (PNVCL) and a functionalized cell-penetrating peptide (H6R6). Doxorubicin (DOX) and oleanolic acid (OA) are loaded into the nanocomposite (H6R6-CS-g-PNVCL). The system displayed a suitable size (∼190 nm), a high DOX loading (13.2%) and OA loading efficiency (7.3%). The tumor microenvironment triggered the nanocomposite to be selectively retained in tumor cells, then releasing the drugs. Both in vitro and in vivo studies showed a significant enhancement in antitumor activity of the co-delivered system in comparison to mono-delivery. This approach which relies on redox, pH and temperature effects utilizing co-delivery nanosystems may be beneficial for future applications in cancer chemotherapy.

Original language	English
Article number	116672
Number of pages	12
Journal	Carbohydrate Polymers
Volume	247
Early online date	23 Jun 2020
DOIs	https://doi.org/10.1016/j.carbpol.2020.116672
Publication status	E-pub ahead of print - 23 Jun 2020

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Chen, X., Niu, S., Bremner, D. H., Zhang, X., Zhang, H., Zhang, Y., Li, S., & Zhu, L-M. (2020). Co-delivery of doxorubicin and oleanolic acid by triple-sensitive nanocomposite based on chitosan for effective promoting tumor apoptosis. Carbohydrate Polymers, 247, [116672]. https://doi.org/10.1016/j.carbpol.2020.116672

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title = "Co-delivery of doxorubicin and oleanolic acid by triple-sensitive nanocomposite based on chitosan for effective promoting tumor apoptosis",

abstract = "Nanocomposites as “stevedores” for co-delivery of multidrugs hold great promise in addressing the drawbacks of traditional cancer chemotherapy. In this work, our strategy presents a new avenue for the stepwise release of two co-delivered agents into the tumor cells. The hybrid nanocomposite consists of a pH-responsive chitosan (CS), a thermosensitive poly(N-vinylcaprolactam) (PNVCL) and a functionalized cell-penetrating peptide (H6R6). Doxorubicin (DOX) and oleanolic acid (OA) are loaded into the nanocomposite (H6R6-CS-g-PNVCL). The system displayed a suitable size (∼190 nm), a high DOX loading (13.2%) and OA loading efficiency (7.3%). The tumor microenvironment triggered the nanocomposite to be selectively retained in tumor cells, then releasing the drugs. Both in vitro and in vivo studies showed a significant enhancement in antitumor activity of the co-delivered system in comparison to mono-delivery. This approach which relies on redox, pH and temperature effects utilizing co-delivery nanosystems may be beneficial for future applications in cancer chemotherapy.",

author = "Xia Chen and Shiwei Niu and Bremner, {David H.} and Xuejing Zhang and Hongmei Zhang and Yanyan Zhang and Shude Li and Li-Min Zhu",

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AU - Chen, Xia

AU - Niu, Shiwei

AU - Bremner, David H.

AU - Zhang, Xuejing

AU - Zhang, Hongmei

AU - Zhang, Yanyan

AU - Li, Shude

AU - Zhu, Li-Min

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AB - Nanocomposites as “stevedores” for co-delivery of multidrugs hold great promise in addressing the drawbacks of traditional cancer chemotherapy. In this work, our strategy presents a new avenue for the stepwise release of two co-delivered agents into the tumor cells. The hybrid nanocomposite consists of a pH-responsive chitosan (CS), a thermosensitive poly(N-vinylcaprolactam) (PNVCL) and a functionalized cell-penetrating peptide (H6R6). Doxorubicin (DOX) and oleanolic acid (OA) are loaded into the nanocomposite (H6R6-CS-g-PNVCL). The system displayed a suitable size (∼190 nm), a high DOX loading (13.2%) and OA loading efficiency (7.3%). The tumor microenvironment triggered the nanocomposite to be selectively retained in tumor cells, then releasing the drugs. Both in vitro and in vivo studies showed a significant enhancement in antitumor activity of the co-delivered system in comparison to mono-delivery. This approach which relies on redox, pH and temperature effects utilizing co-delivery nanosystems may be beneficial for future applications in cancer chemotherapy.

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DO - 10.1016/j.carbpol.2020.116672

M3 - Article

VL - 247

JO - Carbohydrate Polymers

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