Chemotherapy holds a prominent position in contemporary cancer treatment modalities; however, poor water solubility, rapid clearance, and unintended side effects remain significant challenges. To mitigate these issues, various nanoparticlebased delivery systems have been devised to improve the pharmacokinetic and pharmacodynamic profiles of chemotherapeutic drugs. While biocompatible, most of these drug delivery systems include materials that are foreign to the human body. Consequently, it is critical for these materials to be effectively removed from the body to prevent their potential toxicity. In this study, we introduce a nanoparticle-based system that utilizes only hemin, which is naturally found in the body, as an amphiphilic coating agent to facilitate the solubilization of hydrophobic drugs. Camptothecin (CPT), Paclitaxel (PTX), and Sorafenib (SOR) were each formulated into stable hemin-coated nanoparticles (HeminNPs). We demonstrate that hemin-coated CPT nanoparticles exhibit an improved safety profile and therapeutic efficacy compared with the administration of CPT alone in a murine tumor model of triple-negative breast cancer. Consequently, the utilization of HeminNPs demonstrates potential in reducing off-target toxicity and amplifying the therapeutic effectiveness of cancer treatments, which may ultimately contribute to improved treatment outcomes for cancer patients.