Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Yung-Hsing Huang
ORCID logo ,
Mohammad Vakili
,
Ommoleila Molavi
,
Yuen Morrissey
,
Chengsheng Wu
,
Igor Paiva
,
Amir Soleimani
,
Afsaneh Lavasanifar
,
Raymond Lai
*
Version 1 : Received: 10 January 2019 / Approved: 11 January 2019 / Online: 11 January 2019 (15:40:51 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

Abstract

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 hours 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 folds 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.

Keywords

multiple myeloma; STAT3; S3I-1757; nanoparticle; CD38

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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