Acid-active supramolecular anticancer nanoparticles based on cyclodextrin polyrotaxanes damaging both mitochondria and nuclei of tumor cells
As a supramolecular macrocyclic polymer, cyclodextrin (CD) polyrotaxanes (PRs) have many advantages for developing nanomedicines, such as stable chemical composition, abundant functionalized hydroxyl groups, moving across biological barriers, adjustable nanoparticle size and good biocompatibility. Herein, we synthesized a class of acid-active therapeutic nanoparticles comprising a α-CD-based PR polymeric prodrug of PRs-poly(doxorubicin)-co-poly[(ethylene glycol) methyl ether methacrylate] (PR-PDOX-co-POEGMA, denoted as PRMODOX) to reduce drug leakage and selectively deliver drugs into tumor cells, aiming to achieve maximal treatment efficacy of supramolecular therapeutics. The obtained PRMO@DOX showed desirable features of high drug loading rates (>25 wt%), fast cellular uptake, acid-active controlled release, effective anti-tumor activity and low systemic toxicity. Benefiting from its unique amphiphilic nanostructure, PRMO@DOX can form water-soluble prodrug nanoparticles in aqueous media. The acid-active hydrazone bond in the prodrug can break and thus release drug molecules precisely and in a timely manner under an acidic tumor microenvironment, damaging the nuclei and mitochondria of tumor cells. Both in vitro and in vivo experiments clearly demonstrated a remarkable antitumor efficacy of this therapeutic platform, which provided a new strategy for the development of polyrotaxane-based nanomedicine for enhanced cancer therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Biomaterials science - 6(2018), 12 vom: 20. Nov., Seite 3126-3138 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bai, Shuang [VerfasserIn] |
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| Links: |
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| Themen: |
80168379AG |
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| Anmerkungen: |
Date Completed 21.02.2019 Date Revised 21.02.2019 published: Print Citation Status MEDLINE |
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| doi: |
10.1039/c8bm01020j |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM289965411 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a As a supramolecular macrocyclic polymer, cyclodextrin (CD) polyrotaxanes (PRs) have many advantages for developing nanomedicines, such as stable chemical composition, abundant functionalized hydroxyl groups, moving across biological barriers, adjustable nanoparticle size and good biocompatibility. Herein, we synthesized a class of acid-active therapeutic nanoparticles comprising a α-CD-based PR polymeric prodrug of PRs-poly(doxorubicin)-co-poly[(ethylene glycol) methyl ether methacrylate] (PR-PDOX-co-POEGMA, denoted as PRMODOX) to reduce drug leakage and selectively deliver drugs into tumor cells, aiming to achieve maximal treatment efficacy of supramolecular therapeutics. The obtained PRMO@DOX showed desirable features of high drug loading rates (>25 wt%), fast cellular uptake, acid-active controlled release, effective anti-tumor activity and low systemic toxicity. Benefiting from its unique amphiphilic nanostructure, PRMO@DOX can form water-soluble prodrug nanoparticles in aqueous media. The acid-active hydrazone bond in the prodrug can break and thus release drug molecules precisely and in a timely manner under an acidic tumor microenvironment, damaging the nuclei and mitochondria of tumor cells. Both in vitro and in vivo experiments clearly demonstrated a remarkable antitumor efficacy of this therapeutic platform, which provided a new strategy for the development of polyrotaxane-based nanomedicine for enhanced cancer therapy | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
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| 700 | 1 | |a Zhang, Xiaoli |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Xiaoqian |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jiucun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Qiubing |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Xiaoxiao |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Meili |e verfasserin |4 aut | |
| 700 | 1 | |a Xue, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Yuejun |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Zhigang |e verfasserin |4 aut | |
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