Abstract
Current chemotherapy for colorectal cancer (CRC) includes the use of oxaliplatin (Oxa), a first-line cytotoxic drug which, in combination with irinotecan/5-fluorouracil or biologic agents, increases the survival rate of patients. However, the administration of this drug induces side effects that limit its application in patients, making it necessary to develop new tools for targeted chemotherapy. MamC-mediated biomimetic magnetic nanoparticles coupled with Oxa (Oxa-BMNPs) have been previously demonstrated to efficiently reduce the IC50 compared to that of soluble Oxa. However, their strong interaction with the macrophages revealed toxicity and possibility of aggregation. In this scenario, a further improvement of this nanoassembly was necessary. In the present study, Oxa-BMNPs nanoassemblies were enveloped in phosphatidylcholine unilamellar liposomes (both pegylated and non-pegylated). Our results demonstrate that the addition of both a lipid cover and further pegylation improves the biocompatibility and cellular uptake of the Oxa-BMNPs nanoassemblies without significantly reducing their cytotoxic activity in colon cancer cells. In particular, with the pegylated magnetoliposome nanoformulation (a) hemolysis was reduced from 5% to 2%, being now hematocompatibles, (b) red blood cell agglutination was reduced, (c) toxicity in white blood cells was eliminated. This study represents a truly stepforward in this area as describes the production of one of the very few existing nanoformulations that could be used for a local chemotherapy to treat CRC.
Highlights
Biominerals, especially those resulting from a biologically controlled mineralization process, have fascinated numerous researchers over the years due to their specific features and unique properties that are the result of the exquisite degree of control that the organisms have over the mineral formation [1]
energy loss spectroscopy (EELS) show the presence of iron, as expected for magnetite, inside the defined layer observed by Transmission electron microscopy (TEM)
Biomimetic magnetic nanoparticles (BMNPs) (Figure 1A) were uniform well-defined nanoparticles with a diameter of approximately 30–40 nm, while TEM analyses on Oxa-biomimetic nanoparticles (BMLs)-PEG show particles with a diameter of 100–200 nm, enclosing several magnetic nanoparticles per liposome (Figure 1B)
Summary
Biominerals, especially those resulting from a biologically controlled mineralization process, have fascinated numerous researchers over the years due to their specific features and unique properties that are the result of the exquisite degree of control that the organisms have over the mineral formation [1]. 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, in magnetic nanoparticles of different size and morphology (and magnetic properties) compared to those of chemically produced ones, and in nanoparticles with novel surface properties [5] These BMNPs display larger sizes (~40 nm) compared to most commercial chemically synthesized magnetic nanoparticles (MNPs) (≤ 30 nm), and are endowed of (1) a higher blocking temperature while being superparamagnetic at room temperature and (2) high saturation magnetization, these features being consistent with well-structured magnetic nanoparticles with a large magnetic moment per particle. 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
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