Abstract
Colorectal cancer is the third most common malignant disease worldwide, and chemotherapy has been the standard treatment for colorectal cancer. However, the therapeutic effects of chemotherapy are unsatisfactory for advanced and recurrent colorectal cancers. Thus, increasing the treatment efficacy of chemotherapy in colorectal cancer is a must. In this study, doxorubicin (DOX)-loaded tumor-targeting peptide-decorated mPEG-P(Phe-co-Cys) nanoparticles were developed to treat orthotopic colon cancer in mice. The peptide VATANST (STP) can specifically bind with vimentin highly expressed on the surface of colon cancer cells, thus achieving the tumor-targeting effects. The nanoparticles are core-shell structured, which can protect the loaded DOX while passing through the blood flow and increase the circulation time. The disulfide bonds within the nanoparticles are sensitive to the glutathione-rich microenvironment of tumor tissues. Rupture of disulfide bonds of the nanoparticles leads to the continuous release of DOX, thus resulting in the apoptosis of the tumor cells. The in vivo experiments in mice with orthotopic colon cancer demonstrated that the synthesized DOX-loaded tumor-targeting peptide-decorated polypeptide nanoparticles showed properties of drug delivery systems and exhibited good antitumor properties. The synthesized nanoparticles show appropriate properties as one of the drug delivery systems and exhibit good antitumor properties after encapsulating DOX.
Highlights
Colorectal cancer was the third most common malignant disease worldwide, and the number of patients was rising, with approximately 500,000 deaths each year (Jemal et al, 2011; Laroui et al, 2011)
STP could bind with vimentin highly expressed on the surface of colon cancer cells (Kim et al, 2020; Vermani et al, 2020), increasing the tumor-targeting effects of STP-mPEG-P(Phe-co-Cys) nanoparticles (mNPs)/DOX
Vimentin was a kind of epithelial-to-mesenchymal (EMT) marker highly expressed in many cancers, including colorectal cancer (Kim et al, 2020; Vermani et al, 2020)
Summary
Colorectal cancer was the third most common malignant disease worldwide, and the number of patients was rising, with approximately 500,000 deaths each year (Jemal et al, 2011; Laroui et al, 2011). With the innovation of treatment theories, chemotherapy was highlighted. Recent advances in chemotherapy, including the use of irinotecan, oxaliplatin, fluoropyrimidines, cetuximab, bevacizumab, and radiation therapy, have increased the median survival of patients (Ortiz et al, 2012). Advanced and recurrent colorectal cancers were still hard to be cured (Chaudhary et al, 2011). Patients with colorectal cancer needed more efficient chemotherapy (Soster et al, 2012; Prados et al, 2013). With the development of nanotechnology, plenty of nanoscale drug delivery systems (DDSs) have been applied to the chemotherapy drug delivery, such as micelles, vesicles, nanogels, and dendrimer
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