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Article

Synthetic HDL Nanoparticles Delivering Docetaxel and CpG for Chemoimmunotherapy of Colon Adenocarcinoma

1
Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA
2
Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA
3
Department of Neurosurgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA
4
Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA
5
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(5), 1777; https://doi.org/10.3390/ijms21051777
Received: 12 November 2019 / Revised: 19 February 2020 / Accepted: 3 March 2020 / Published: 5 March 2020
(This article belongs to the Special Issue Lipoprotein Nanoparticles for Diagnosis and Therapy)
Colon carcinomas comprise over two-thirds of all colorectal cancers with an overall 5-year survival rate of 64%, which rapidly decreases to 14% when the cancer becomes metastatic. Depending on the stage of colon carcinoma at diagnosis, patients can undergo surgery to attempt complete tumor resection or move directly to chemotherapy with one or a combination of drugs. As with most cancers, colon carcinomas do not always respond to chemotherapies, so targeted therapies and immunotherapies have been developed to aid chemotherapy. We report the development of a local combination therapy for colon carcinoma whereby chemo- and immunotherapeutic entities are delivered intratumorally to maximize efficacy and minimize off-target side effects. A hydrophobic chemotherapeutic agent, docetaxel (DTX), and cholesterol-modified Toll-like receptor 9 (TLR9) agonist CpG (cho-CpG) oligonucleotide are co-loaded in synthetic HDL (sHDL) nanodiscs. In vivo survival analysis of MC-38 tumor-bearing mice treated intratumorally with DTX-sHDL/CpG (median survival; MS = 43 days) showed significant improvement in overall survival compared to mice treated with single agents, free DTX (MS = 23 days, p < 0.0001) or DTX-sHDL (MS = 28 days, p < 0.0001). Two of seven mice treated with DTX-sHDL/CpG experienced complete tumor regression. None of the mice experienced any systemic toxicity as indicated by body weight maintenance and normal serum enzyme and protein levels. In summary, we have demonstrated that chemo- and immunotherapies can be co-loaded into sHDLs, delivered locally to the tumor, and can be used to improve survival outcomes significantly compared to chemotherapy alone. View Full-Text
Keywords: co-delivery; chemotherapy; immunotherapy; colon carcinoma co-delivery; chemotherapy; immunotherapy; colon carcinoma
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MDPI and ACS Style

Scheetz, L.M.; Yu, M.; Li, D.; Castro, M.G.; Moon, J.J.; Schwendeman, A. Synthetic HDL Nanoparticles Delivering Docetaxel and CpG for Chemoimmunotherapy of Colon Adenocarcinoma. Int. J. Mol. Sci. 2020, 21, 1777. https://doi.org/10.3390/ijms21051777

AMA Style

Scheetz LM, Yu M, Li D, Castro MG, Moon JJ, Schwendeman A. Synthetic HDL Nanoparticles Delivering Docetaxel and CpG for Chemoimmunotherapy of Colon Adenocarcinoma. International Journal of Molecular Sciences. 2020; 21(5):1777. https://doi.org/10.3390/ijms21051777

Chicago/Turabian Style

Scheetz, Lindsay M., Minzhi Yu, Dan Li, María G. Castro, James J. Moon, and Anna Schwendeman. 2020. "Synthetic HDL Nanoparticles Delivering Docetaxel and CpG for Chemoimmunotherapy of Colon Adenocarcinoma" International Journal of Molecular Sciences 21, no. 5: 1777. https://doi.org/10.3390/ijms21051777

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