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

International Journal of Molecular Sciences
Lindsay M ScheetzAnna Schwendeman

Abstract

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 se...Continue Reading

References

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Citations

Sep 25, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Dennis Pedersbæk, Jens B Simonsen
Apr 16, 2021·Advanced Drug Delivery Reviews·M Brittany JohnsonKirill A Afonin
Apr 19, 2021·Journal of Nanobiotechnology·Rafieh BagherifarYousef Javadzadeh
May 1, 2021·Pharmaceutics·Tianqi WangJie Shen

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Methods Mentioned

BETA
confocal microscopy
dynamic laser
FACS
Assay

Software Mentioned

ImageJ

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