Hyaluronic acid–doxorubicin nanoparticles for targeted treatment of colorectal cancer

Abstract

Colorectal cancer, common in both men and women, occurs when tumors form in the linings of the colon. Common treatments of colorectal cancer include surgery, chemotherapy, and radiation therapy; however, many colorectal cancer treatments often damage healthy tissues and cells, inducing severe side effects. Conventional chemotherapeutic agents such as doxorubicin (Dox) can be potentially used for the treatment of colorectal cancer; however, they suffer from limited targeting and lack of selectivity. Here, we report that doxorubicin complexed to hyaluronic acid (HA) (HA-Dox) exhibits an unusual behavior of high accumulation in the intestines for at least 24 hr when injected intravenously. Intravenous administrations of HA-Dox effectively preserved the mucosal epithelial intestinal integrity in a chemical induced colon cancer model in mice. Moreover, treatment with HA-Dox decreased the expression of intestinal apoptotic and inflammatory markers. The results suggest that HA-Dox could effectively inhibit the development of colorectal cancer in a safe manner, which potentially be used a promising therapeutic option.

Design of Bio-Responsive Hyaluronic Acid–Doxorubicin Conjugates for the Local Treatment of Glioblastoma

“…HA has been extensively used to coat various nanocarriers, taking advantage of its intrinsic targeting towards CD44-overexpressed tumors, including GBM [20][21][22]. HA has been conjugated to therapeutics, such as paclitaxel [23,24], doxorubicin [25,26], and cisplatin [27], either alone or in combination [28,29], to improve drug efficacy and reduce toxicity. HA can act as a trojan horse to promote the cell uptake of the conjugated drug.…”

Current Landscape in Organic Nanosized Materials Advances for Improved Management of Colorectal Cancer Patients

“…More, CD44 is part of the molecular signature of cancer stem cells, a subpopulation of cells involved in tumor initiation, growth, and metastasis [ 116 , 117 ]. Therefore, HA-decorated nanoparticles could target both tumor cells overexpressing CD44 as well as cancer stem cells [ 118 , 119 , 120 , 121 , 122 ].…”

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

“…Colorectal cancer is the third leading cause of cancer-related mortality in men and women [ 1 ]. Treatments such as chemotherapy, surgery, and radiotherapy are key current methods used to treat colorectal cancer.…”

“…Although chemotherapeutic agents have proved useful in cancer treatment, patients experience severe side effects, for example, hair loss, fatigue, nausea and vomiting, constipation or diarrhea, anemia, immunosuppression, and other organ toxicities [ 5 , 6 ]. Doxorubicin (Dox), an anthracycline derivative, has been applied in various curative drug combinations for the treatment of ovarian, breast, bladder, lung, and colon cancers [ 1 , 7 ]. Its mechanism of action is intercalating the DNA base pairs and inhibiting DNA and RNA replication that causes DNA damage and induces cellular apoptosis [ 8 ], and it is a very potent and cost-effective compound compared with other therapeutic agents [ 9 ].…”