Abstract
An infusion-dialysis based procedure has been developed as an approach to isolate organic nanoparticles from green tea. Tea nanoparticle (TNP) can effectively load doxorubicin (DOX) via electrostatic and hydrophobic interactions. We established an ABCB1 overexpressing tumor xenograft mouse model to investigate whether TNP can effectively deliver DOX into tumors and bypass the efflux function of the ABCB1 transporter, thereby increasing the intratumoral accumulation of DOX and potentiating the anticancer activity of DOX. MTT assays suggested that DOX-TNP showed higher cytotoxicity toward CCD-18Co, SW620 and SW620/Ad300 cells than DOX. Animal study revealed that DOX-TNP resulted in greater inhibitory effects on the growth of SW620 and SW620/Ad300 tumors than DOX. In pharmacokinetics study, DOX-TNP greatly increased the SW620 and SW620/Ad300 intratumoral concentrations of DOX. But DOX-TNP had no effect on the plasma concentrations of DOX. Furthermore, TNP is a safe nanocarrier with excellent biocompatibility and minimal toxicity. Ex vivo IHC analysis of SW620 and SW620/Ad300 tumor sections revealed evidence of prominent antitumor activity of DOX-TNP. In conclusion, our findings suggested that natural nanomaterials could be useful in combating multidrug resistance (MDR) in cancer cells and potentiating the anticancer activity of chemotherapeutic agents in cancer treatment.
Highlights
Cancer is well defined as a disease in which abnormal cells divide without control and invade nearby tissues, and is often clinically referred to as tumor or malignant neoplasm
In order to investigate the cytotoxicity of DOX, doxorubicin-loaded tea nanoparticles (DOXTNP) and Tea nanoparticle (TNP) on different human normal and cancer cell lines, MTT assays were performed using a human normal colon fibroblast cell line CCD-18Co, a human colon cancer cell line SW620, and its doxorubicin-selected ABC transporter subfamily B member 1 (ABCB1) overexpressing subline SW620/Ad300
It was found that DOX-loaded Tea nanoparticle (DOX-TNP) had more potent inhibitory effect than DOX on the growth of SW620 tumors over an 18-day treatment period
Summary
Cancer is well defined as a disease in which abnormal cells divide without control and invade nearby tissues, and is often clinically referred to as tumor or malignant neoplasm. Cancer has been ranked as the second most primary cause of death after cardiovascular diseases in the world [1]. Cancer therapy usually includes surgery, radiation therapy, chemotherapy and combination therapy. As a first-line treatment for various cancers, chemotherapy uses drugs with different chemical structures and mechanisms of action. Chemotherapeutic drugs combat cancer by disturbing cell proliferation and targeting the fast-dividing cancer cells [3]. Long-term cancer chemotherapy often results in the development of resistance to anticancer drugs and attenuates the efficacy of cancer treatment, leading to higher chances of “cancer relapse” [4]
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