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Issue 45, 2019
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Development of multi-drug loaded PEGylated nanodiamonds to inhibit tumor growth and metastasis in genetically engineered mouse models of pancreatic cancer

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Nanomedicine, however, offers new opportunities to facilitate drug delivery in PDAC. Our previous work has shown that poly(ethylene glycol)-functionalized nanodiamond (ND) mediated drug delivery offered a considerable improvement over free drug in PDAC. Inspired by this result and guided by molecular simulations, we opted for simultaneous loading of irinotecan and curcumin in ultra-small PEGylated NDs (ND-IRT + CUR). We observed that ND-IRT + CUR was more efficacious in killing AsPC-1 and PANC-1 cells than NDs with single drugs. Using NDs functionalized with a near-infrared (NIR) dye, we demonstrated the preferential localization of the NDs in tumors and metastatic lesions. We further demonstrate that ND-IRT + CUR is capable of producing pronounced anti-tumor effects in two different clinically relevant, immune-competent genetic models of PDAC. Cytokine profiling indicated that NDs with or without drugs downregulated the expression of IL-10, a key modulator of the tumor microenvironment. Thus, using a combination of in silico, in vitro, and in vivo approaches, we show for the first time the remarkable anti-tumor efficacy of PEGylated NDs carrying a dual payload of irinotecan plus curcumin. These results highlight the potential use of such nano-carriers in the treatment of patients with pancreatic cancer.

Graphical abstract: Development of multi-drug loaded PEGylated nanodiamonds to inhibit tumor growth and metastasis in genetically engineered mouse models of pancreatic cancer

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Supplementary files

Article information


Submitted
28 Jun 2019
Accepted
09 Oct 2019
First published
11 Nov 2019

Nanoscale, 2019,11, 22006-22018
Article type
Paper

Development of multi-drug loaded PEGylated nanodiamonds to inhibit tumor growth and metastasis in genetically engineered mouse models of pancreatic cancer

V. S. Madamsetty, K. Pal, S. Keshavan, T. R. Caulfield, S. K. Dutta, E. Wang, B. Fadeel and D. Mukhopadhyay, Nanoscale, 2019, 11, 22006
DOI: 10.1039/C9NR05478B

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