Abstract
Conventional chemotherapy against colorectal cancer (CRC), the third most common cancer in the world, includes oxaliplatin (Oxa) which induces serious unwanted side effects that limit the efficiency of treatment. Therefore, alternative therapeutic approaches are urgently required. In this work, biomimetic magnetic nanoparticles (BMNPs) mediated by MamC were coupled to Oxa to evaluate the potential of the Oxa–BMNP nanoassembly for directed local delivery of the drug as a proof of concept for the future development of targeted chemotherapy against CRC. Electrostatic interactions between Oxa and BMNPs trigger the formation of the nanoassembly and keep it stable at physiological pH. When the BMNPs become neutral at acidic pH values, the Oxa is released, and such a release is greatly potentiated by hyperthermia. The coupling of the drug with the BMNPs improves its toxicity to even higher levels than the soluble drug, probably because of the fast internalization of the nanoassembly by tumor cells through endocytosis. In addition, the BMNPs are cytocompatible and non-hemolytic, providing positive feedback as a proof of concept for the nanoassembly. Our study clearly demonstrates the applicability of Oxa–BMNP in colon cancer and offers a promising nanoassembly for targeted chemotherapy against this type of tumor.
Highlights
Colorectal cancer (CRC) is the third most common cancer in the world with an estimated 1,096,601 new cases and 551,269 deaths in 2018, respectively [1]
The kinetics of Oxa adsorption over time shows that the system reached equilibrium at about 72 h (Figure 2A)
The results from the present study demonstrate that biomimetic magnetic nanoparticles (BMNPs) can be efficiently coupled to Oxa to form Oxa–BMNP nanoassemblies
Summary
Colorectal cancer (CRC) is the third most common cancer in the world with an estimated 1,096,601 new cases and 551,269 deaths in 2018, respectively [1]. Oxa is a member of a class of platinum-based compounds that act as alkylating cytotoxic agents It inhibits DNA replication and it is currently used for the treatment of CRC, providing antitumor activity in the treatments of pancreatic, gastric, ovarian, bladder, breast, small- and non-small-cell lung, and head and neck cancer [9,10,11]. In the case of Oxa, these side effects are progressive peripheral sensory neuropathy, acute mild neuropathy, diarrhea, vomiting, and hematological suppression [12,13]. Factors such as the emergence of resistance (whether intrinsic or acquired), the drug pharmacokinetics, and drug degradation before reaching the tumor tissue limit the efficiency of these treatments [2,14]. Targeted chemotherapy is being explored for CRC at the present with the goal of minimizing (or avoiding) secondary effects linked to the systemic distribution of the drug, to increase the efficiency of the treatment and to reduce the cost [15]
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