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Cancers 2019, 11(2), 248;

Decoration of Anti-CD38 on Nanoparticles Carrying a STAT3 Inhibitor Can Improve the Therapeutic Efficacy Against Myeloma

Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2R3, Canada
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2H7, Canada
Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz P.O. Box 51664-14766, East Azerbaijan Province, Iran
Author to whom correspondence should be addressed.
C.W. is now with the Department of Pathology, University of California San Diego, San Diego, CA 92093, USA.
Received: 10 January 2019 / Revised: 4 February 2019 / Accepted: 14 February 2019 / Published: 20 February 2019
(This article belongs to the Special Issue Targeting STAT3 and STAT5 in Cancer)
PDF [2570 KB, uploaded 20 February 2019]
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STAT3 is an oncoprotein which has been shown to contribute to drug resistance in multiple myeloma (MM). Nonetheless, the clinical utility of STAT3 inhibitors in treating MM has been limited, partly related to some of their pharmacologic properties. To overcome these challenges, our group had previously packaged STAT3 inhibitors using a novel formulation of nanoparticles (NP) and found encouraging results. In this study, we aimed to further improve the pharmacologic properties of these NP by decorating them with monoclonal anti-CD38 antibodies. NP loaded with S3I-1757 (a STAT3 inhibitor), labeled as S3I-NP, were generated. S3I-NP decorated with anti-CD38 (labeled as CD38-S3I-NP) were found to have a similar nanoparticular size, drug encapsulation, and loading as S3I-NP. The release of S3I-1757 at 24 h was also similar between the two formulations. Using Cy5.5 labeling of the NP, we found that the decoration of anti-CD38 on these NP significantly increased the cellular uptake by two MM cell lines (p < 0.001). Accordingly, CD38-S3I-NP showed a significantly lower inhibitory concentration at 50% (IC50) compared to S3I-NP in two IL6-stimulated MM cell lines (p < 0.001). In a xenograft mouse model, CD38-S3I-NP significantly reduced the tumor size by 4-fold compared to S3I-NP on day 12 after drug administration (p = 0.006). The efficacy of CD38-S3I-NP in suppressing STAT3 phosphorylation in the xenografts was confirmed by using immunocytochemistry and Western blot analysis. In conclusion, our study suggests that the decoration of anti-CD38 on NP loaded with STAT3 inhibitors can further improve their therapeutic effects against MM. View Full-Text
Keywords: multiple myeloma; STAT3; S3I-1757; nanoparticle; CD38 multiple myeloma; STAT3; S3I-1757; nanoparticle; CD38

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Huang, Y.-H.; Vakili, M.R.; Molavi, O.; Morrissey, Y.; Wu, C.; Paiva, I.; Soleimani, A.H.; Sanaee, F.; Lavasanifar, A.; Lai, R. Decoration of Anti-CD38 on Nanoparticles Carrying a STAT3 Inhibitor Can Improve the Therapeutic Efficacy Against Myeloma. Cancers 2019, 11, 248.

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