Abstract

Mucin 1 (MUC1) is an important molecular target for cancer treatment because it is overexpressed in most adenocarcinomas. In this study, a new MUC1-targeted drug delivery system was assembled using an aptamer (Apt) that could recognize MUC1 and a DNA tetrahedron (Td) that could carry doxorubicin (Dox) within its DNA structure. The complex thus formed (Apt-Td) had an average size of 12.38 nm and was negatively charged. Similar to the MUC1 aptamer, the Apt-Td could preferentially bind with MUC1-positive MCF-7 breast cancer cells. A drug loading experiment revealed that each Apt-Td complex could carry approximately 25 Dox molecules. Moreover, Apt-Td selectively delivered Dox into the MUC1-positive breast cancer cells but reduced Dox uptake by the MUC1-negative control cells. Dox-loaded Apt-Td also induced a significantly higher cytotoxicity to the MUC1-positive cancer cells versus the MUC1-negative control cells in vitro (p<0.01). These results suggest that Apt-Td may potentially serve as a drug carrier in the targeted treatment of MUC1-expressing breast cancers.

Highlights

  • Chemotherapy is the primary treatment for advanced metastatic breast cancer

  • The original Mucin 1 (MUC1) aptamer was extended with an extra tail (Apt-tail) to serve as a sticky end

  • The results showed that the average size of Td was 10.40 nm before coupling with the aptamers

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Summary

Introduction

Chemotherapy is the primary treatment for advanced metastatic breast cancer. conventional chemotherapy faces the major obstacle of systematic toxicity [1, 2]. Because most conventional anticancer agents cannot distinguish between normal and tumor cells, they produce side effects, such as nausea, hair loss, neutropenia, peripheral neuropathies, renal failure, encephalopathy, and cardiac toxicity [3,4,5,6,7,8]. These adverse reactions seriously limit the efficacy of chemotherapy to eliminate metastatic cancer cells because the drug dosage and treatment frequency are often curbed by patients’ intolerance to treatment-associated side effects. Exploring new therapeutic strategies for advanced cancer is a matter of medical importance

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