Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study

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.

Biomimetic Magnetoliposomes as Oxaliplatin Nanocarriers: In Vitro Study for Potential Application in Colon Cancer

“…The functionalization of BMNPs with Oxaliplatin (Oxa) to form the nanoassembly Oxa-BMNPs was performed as detailed in [14]. Five milligrams of BMNPs were mixed with 1 mL of Oxa (2 mg/mL) in PBS buffer.…”

“…The encapsulation efficiency was 80 ± 10%. The Oxa-BMNPs nanoassemblies used in the present study have been previously characterized in Jabalera et al [14].…”

“…However, these MmsF-mediated magnetic nanoparticles are still not characterized enough to determine whether or not they could be of use in nanotechnology. On the contrary, MamC-mediated biomimetic nanoparticles (here referred as BMNPs) have demonstrated their potential as promising drug nanocarriers [5,6,14,15] and as hyperthermia agents [16,17], opening the possibility of a combined therapy by using the same nanoplatform. MamC controls magnetite nucleation and growth by both template and ionotropic effects [18], remaining attached to the nanoparticles and forming a nanocomposite (95 wt% magnetite + 5 wt% MamC) that results, not only in magnetic nanoparticles of different size and morphology (and thus magnetic properties) compared to those of chemically produced ones, but also in nanoparticles with novel surface properties [5].…”

“…Moreover, in terms of surface properties, MamC confers new surface properties to these BMNPs, in particular, an isoelectric point (pI) at pH 4.4 which allows functionalization based on electrostatic interactions and drug release being pH dependent. In fact, a previous proof of concept showed that BMNPs were biocompatible and could be coupled with Oxaliplatin (Oxa) [14]. Therefore, these MamC-mediated BMNPs have been proposed as efficient nanocarriers [5,6,14,15] of a number of molecules offering crucial advantages over the use of inorganically synthesized magnetic nanoparticles to this end.…”

“…The use of our BMNPs as drug nanocarriers (Oxa) and as hyperthermia agents have the advantage over the abovementioned systems of: (1) the magnetic guidance allow both the control of where the drug is delivered and the concentration of the drug at the target thanks to possibility of a magnetic guidance and (2) the potentiation of the cytotoxic effect by using a combined therapy based on chemotherapy and magnetic hyperthermia [14]. Oxa-BMNP nanoassemblies increased the cytotoxic effect of the drug to even higher level than that caused by soluble Oxa, probably due to the internalization of BMNPs in the tested colon cancer cells.…”