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 journalArticlepeer-review

    1 Citation (Scopus)

    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 languageEnglish
    Article number116672
    Number of pages12
    JournalCarbohydrate Polymers
    Volume247
    Early online date23 Jun 2020
    DOIs
    Publication statusPublished - 1 Nov 2020

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