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

Cancers
Yung-Hsing HuangRaymond Lai

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 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 t...Continue Reading

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Citations

May 28, 2019·Cancers·Phyllis S Y ChongSanjay de Mel
Mar 12, 2020·Phytotherapy Research : PTR·Milad AshrafizadehSaeed Samarghandian
Oct 2, 2019·Cells·Milad AshrafizadehGautam Sethi
Jan 23, 2020·Cancers·Marie Brachet-BotineauFabrice Gouilleux
Jul 28, 2020·Cancers·Elvin D de AraujoRichard Moriggl
Feb 29, 2020·Anti-cancer Agents in Medicinal Chemistry·Milad AshrafizadehAmirhossein Sahebkar
Oct 31, 2020·Cancers·Daniela IannazzoAlessandra Bitto
Mar 18, 2021·Journal of Oncology·Sanyog DwivediLuis F Montaño
Mar 17, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ejaj AhmadSundeep Singh Saluja
Jul 23, 2019·Advanced Drug Delivery Reviews·Joseph M CasterAndrew Z Wang
Aug 9, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Wenxing GuZhiyuan Zhong
Sep 28, 2021·Therapeutic Delivery·Neret Pujol-NavarroPaul A Mulheran

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Methods Mentioned

BETA
xenograft
flow cytometry
Protein Assay
X-ray

Software Mentioned

Excel
Living Image
GraphPad Prism
Graph Prism

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