Preclinical Evaluation of an Epidermal Growth Factor Receptor-Targeted Doxorubicin-Peptide Conjugate: Toxicity, Biodistribution, and Efficacy in Mice.

Doxorubicin (DOX) is known to induce apoptosis and necrosis in healthy tissue resulting in unwanted toxicities. To improve the ability of DOX to more specifically target tumors and minimize undesirable side effects, conjugation of DOX with epidermal growth factor receptor (EGFR)--binding peptide (DOX-EBP) has been developed to deliver DOX to EGFR-overexpressing neoplastic cells. Here, we investigated whether DOX-EBP was able to reduce toxicity and enhance anticancer efficacy in vivo through receptor-mediated targeted delivery system. Nude mice were treated with DOX or DOX-EBP to estimate general toxicity, normal tissue damage, biodistribution, and antitumor efficacy. In addition, the expression levels of EGFR in tumor tissues and normal organs were investigated by Western blotting, and their mRNA expression was analyzed by reverse transcription PCR. This study demonstrated that DOX-EBP was able to effectively decrease the distribution of DOX in normal tissues without EGFR overexpressing and reduce DOX-induced toxicity. On the other hand, the research also confirmed that DOX-EBP was able to preferentially accumulate DOX in EGFR-overexpressing tumor tissues and showed the enhanced anticancer efficacy over free DOX. DOX-EBP could be used for receptor-targeted chemotherapy with less toxicity and greater efficacy of tumor cells overexpressing EGFR. DOX-EBP conjugate is a good therapeutic agent for cancer treatment.