1. Academic Validation
  2. Fucoidan-coated nanoparticles target radiation-induced P-selectin to enhance chemoradiotherapy in murine colorectal cancer

Fucoidan-coated nanoparticles target radiation-induced P-selectin to enhance chemoradiotherapy in murine colorectal cancer

  • Cancer Lett. 2021 Mar 1;500:208-219. doi: 10.1016/j.canlet.2020.11.021.
Allison N DuRoss 1 Madeleine R Landry 1 Charles R Thomas Jr 2 Megan J Neufeld 3 Conroy Sun 4
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, Oregon State University, 2730 S Moody Ave, Portland, OR, 97201, USA.
  • 2 Department of Radiation Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
  • 3 Department of Pharmaceutical Sciences, Oregon State University, 2730 S Moody Ave, Portland, OR, 97201, USA. Electronic address: [email protected].
  • 4 Department of Pharmaceutical Sciences, Oregon State University, 2730 S Moody Ave, Portland, OR, 97201, USA; Department of Radiation Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA. Electronic address: [email protected].
Abstract

Colorectal Cancer (CRC) is a leading cause of cancer-related death for both men and women, highlighting the need for new treatment strategies. Advanced disease is often treated with a combination of radiation and cytotoxic agents, such as DNA damage repair inhibitors and DNA damaging agents. To optimize the therapeutic window of these multimodal therapies, advanced nanomaterials have been investigated to deliver sensitizing agents or enhance local radiation dose deposition. In this study, we demonstrate the feasibility of employing an inflammation targeting nanoscale metal-organic framework (nMOF) platform to enhance CRC treatment. This novel formulation incorporates a fucoidan surface coating to preferentially target P-Selectin, which is over-expressed or translocated in irradiated tumors. Using this radiation stimulated delivery strategy, a combination PARP Inhibitor (talazoparib) and chemotherapeutic (temozolomide) drug-loaded hafnium and 1,4-dicarboxybenzene (Hf-BDC) nMOF was evaluated both in vitro and in vivo. Significantly, these drug-loaded P-Selectin targeted nMOFs (TT@Hf-BDC-Fuco) show improved tumoral accumulation over multiple controls and subsequently enhanced therapeutic effects. The integrated radiation and nanoformulation treatment demonstrated improved tumor control (reduced volume, density, and growth rate) and increased survival in a syngeneic CRC mouse model. Overall, the data from this study support the continued investigation of radiation-priming for targeted drug delivery and further consideration of nanomedicine strategies in the clinical management of advanced CRC.

Keywords

Hafnium; Inflammation; MOF; Talazoparib; Temozolomide.

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