Doxorubicin-Loaded Tumor-Targeting Peptide-Decorated Polypeptide Nanoparticles for Treating Primary Orthotopic Colon Cancer

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.

Synthesis of Polyethylene Glycol Diacrylate/Acrylic Acid Nanoparticles as Nanocarriers for the Controlled Delivery of Doxorubicin to Colorectal Cancer Cells

“…Pharmaceutics 2022, 14, x FOR PEER REVIEW differences [42,43]. Furthermore, the release behavior of Dox from different kin was found to collate to our findings.…”

“…These factors were related to the release profile of Dox-NPs obtained [ 40 , 41 ]. According to the literature review on Dox delivery to colorectal cancer, similar findings were found; for example, Lui et al (2021) as well as Abedi et al (2021) reported that the release of Dox was pH dependent, where a more rapid release was found at lower pH value, regardless of the NPs’ construction differences [ 42 , 43 ]. Furthermore, the release behavior of Dox from different kinds of NPs was found to collate to our findings.…”

Recent Update on Bacteria as a Delivery Carrier in Cancer Therapy: From Evil to Allies

“…Biological therapeutics, for example, antibodies, peptide-mimetics, and a few cytokines showed target-specific effects, and they are relatively safer to be used in cancer treatment ( 5 ). Furthermore, studies also showed that engineered nanoparticles have selectivity in detecting and destroying tumour cells ( 6 – 9 ). However, physiological and physical limitations for incorporating engineered nanoparticles in cancer treatment still exist.…”

“…However, physiological and physical limitations for incorporating engineered nanoparticles in cancer treatment still exist. These include protein adsorption, phagocytic sequestration, diffusion, flow, and shear forces which reduce the extent of diffusion of nanoparticles to the tumour cells ( 6 , 10 ).…”

Induction of apoptosis and cell cycle arrest in colorectal cancer cells by novel anticancer metabolites of Streptomyces sp. 801

“…Streptomyces , as mentioned, contain anti-cancer compounds that can be used as chemotherapy drugs [ 28 ] that is often used treat to control advanced cancers to enhance survival [ 29 ]. Among these cancers that usually spread to other organs, chemotherapy is the most common treatment for CRC [ 30 , 31 ] that many lifestyle factors, obesity and dietary patterns are linked to the cancer [ 32 , 33 ].…”