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Π electron-stabilized polymeric micelles potentiate docetaxel therapy in advanced-stage gastrointestinal cancer

 
: Liang, C.; Bai, X.; Qi, C.; Sun, Q.; Han, X.; Lan, T.; Zhang, H.; Zheng, X.; Liang, R.; Jiao, J.; Zheng, Z.; Fang, J.; Lei, P.; Wang, Y.; Möckel, D.; Metselaar, J.M.; Storm, G.; Hennink, W.E.; Kiessling, F.; Wei, H.; Lammers, T.; Shi, Y.; Wei, B.

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Biomaterials 266 (2021), Art. 120432
ISSN: 0142-9612
ISSN: 1878-5905
Englisch
Zeitschriftenaufsatz
Fraunhofer MEVIS ()

Abstract
Gastrointestinal (GI) cancers are among the most lethal malignancies. The treatment of advanced-stage GI cancer involves standard chemotherapeutic drugs, such as docetaxel, as well as targeted therapeutics and immunomodulatory agents, all of which are only moderately effective. We here show that Π electron-stabilized polymeric micelles based on PEG-b-p(HPMAm-Bz) can be loaded highly efficiently with docetaxel (loading capacity up to 23 wt%) and potentiate chemotherapy responses in multiple advanced-stage GI cancer mouse models. Complete cures and full tumor regression were achieved upon intravenously administering micellar docetaxel in subcutaneous gastric cancer cell line-derived xenografts (CDX), as well as in CDX models with intraperitoneal and lung metastases. Nanoformulated docetaxel also outperformed conventional docetaxel in a patient-derived xenograft (PDX) model, doubling the extent of tumor growth inhibition. Furthermore, micellar docetaxel modulated the tumor immune microenvironment in CDX and PDX tumors, increasing the ratio between M1-and M2-like macrophages, and toxicologically, it was found to be very well-tolerated. These findings demonstrate that Π electron-stabilized polymeric micelles loaded with docetaxel hold significant potential for the treatment of advanced-stage GI cancers.

: http://publica.fraunhofer.de/dokumente/N-615063.html