Integrin alpha V beta 3 targeted dendrimer-rapamycin conjugate reduces fibroblast-mediated prostate tumor progression and metastasis.

Abstract:

:Therapeutic strategies targeting both cancer cells and associated cells in the tumor microenvironment offer significant promise in cancer therapy. We previously reported that generation 5 (G5) dendrimers conjugated with cyclic-RGD peptides target cells expressing integrin alpha V beta 3. In this study, we report a novel dendrimer conjugate modified to deliver the mammalian target of rapamycin (mTOR) inhibitor, rapamycin. In vitro analyses demonstrated that this drug conjugate, G5-FI-RGD-rapamycin, binds to prostate cancer (PCa) cells and fibroblasts to inhibit mTOR signaling and VEGF expression. In addition, G5-FI-RGD-rapamycin inhibits mTOR signaling in cancer cells more efficiently under proinflammatory conditions compared to free rapamycin. In vivo studies established that G5-FI-RGD-rapamycin significantly inhibits fibroblast-mediated PCa progression and metastasis. Thus, our results suggest the potential of new rapamycin-conjugated multifunctional nanoparticles for PCa therapy.

journal_name

J Cell Biochem

authors

Hill EE,Kim JK,Jung Y,Neeley CK,Pienta KJ,Taichman RS,Nor JE,Baker JR Jr,Krebsbach PH

doi

10.1002/jcb.26727

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

8074-8083

issue

10

eissn

0730-2312

issn

1097-4644

journal_volume

119

pub_type

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