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

In the paper

“(a) hemolysis was reduced from 5% to 2%, being now hematocompatibles”

In the paper

“Identically, MNPs showed an average size value of 20 nm, while that for IMLs and IMLs-PEG was of 100 and 200 nm (Figure S1).”

In the paper

“while TEM analyses on Oxa-BMLs-PEG show particles with a diameter of 100–200 nm, enclosing several magnetic nanoparticles per liposome (Figure 1B).”

In the paper

“The polydispersity index (PDI) of these samples were 0.253 ± 0.009, 0.162 ± 0.004, 0.38 ± 0.01 and 0.36 ± 0.02, respectively, which indicates the good dispersity of the samples.”

In the paper

“Dynamic light scattering (DLS) analysis show that the hydrodynamic diameters (Table S1) of the BMLs and Oxa-BMLs-PEG passed through a 100 nm extruder were of 98 ± 2 nm and 134.1 ± 0.9 nm, respectively”

In the paper

“BMNPs (Figure 1A) were uniform well-defined nanoparticles with a diameter of approximately 30–40 nm”

In the paper

“when looking closely to the dark halo resulting from the magnet treatment in non-pegylated nanoformulations, it can be concluded that it is created by non-internalized ones, which does not occur in pegylated nanoformulations.”

In the paper

“In all cases there are significant differences (p < 0.05) between the IC50 of the treatments in the different lines except for CCD18 (all the treatments), Oxa-BMLs 200 nm in HT29 and the Oxa-BMLs-PEG 200 nm in SW480.”

In the paper

“In contrast, LIP (Figure 3(A1),(A2)) and BMLs (Figure 3(A3)) induce a ~ 20% toxicity regardless of the dose (with the exception of 200 nm BMLs in which a dose dependent toxicity is observed; Figure 3(A4)).”

In the paper

“the administration of BMNPs reduces such Fe internalization, because the nanoformulations adhere to the surface and only a small proportion is internalized.”

In the paper

“The hysteresis loop of Oxa-MBLs-PEG showed a typical ferromagnetic behavior at 5 K, while at 300 K, these formulations showed zero coercivity, which indicates their superparamagnetic character”

In the paper

“our results demonstrated that BMLs-PEG were non-toxic to WBC both at 1 and 12 h of exposure by contrast to uncovered NPs in addition to observing a recovery of viability in most treatments after 12 h of exposure such as has been previously described [14].”

What the sources say

• Check pendingcites [14] Jabalera, Y., Garcia-Pinel, B., Ortiz, R., Iglesias, G., Cabeza, L., Prados, J., Jimenez-Lopez, C., and Melguizo, C. (2019). Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study. Pharmaceutics, 11. source

In the paper

“A reduction in the IC50 of free OXA is observed in most tumor cell lines when treated with pegylated nanoformulations, being especially remarkable such reduction in HT29.”

In the paper

“This event can be observed more noticeably for BMLs than for IMLs, and for the 200 nm size.”

In the paper

“On the other hand, in MC38, the administration of IMLs-PEG at high doses is toxic, however this toxicity is lower than that observed with the administration of free iron.”

In the paper

“Both BMLs and Oxa-BMLs-PEG are negatively charged at pH 7.4, (ζ potential of −20.4 ± 0.9 mV and –27.3 ± 0.4, respectively, Figure 1E and Table S1).”

In the paper

“however, with pegylation, their percentage of hemolysis decreases to ~1% and <2% (respectively), being then considered biocompatible (Figure 2A,B) [39].”

What the sources say

• ?Not checked — no full text of the sourcecites [39] Schlenk, 2017, Comprehensive analysis of the in vitro and ex ovo hemocompatibility of surface engineered iron oxide nanoparticles for biomedical applications, Arch. Toxicol. source

In the paper

“In fact, BMLs-PEG accumulations start being observed inside the cell after 2 h of exposure and continue at 24 h.”

In the paper

“In the context of toxicity for RAW 264.7 cell line (Figure 3B), our results demonstrate that the pegylated nanoformulations are more toxic than non-pegylated ones, being that especially true for IMLs.”

In the paper

“Only IML pegylation induced a slight increase on their hemolysis capacity (1% to ~2%), although within the normal range of hemolysis that is considered biocompatible (0–2%) [47].”

What the sources say

• ?Not checked — no full text of the sourcecites [47] Raguraman, 2020, Comparative ecotoxicity assessment of magnetosomes and magnetite nanoparticles, Int. J. Environ. Health Res. source

In the paper

“In comparison to our previous studies [14], the addition of a lipid cover to the nanoparticles improve their dispersion, eliminating the agglutination of erythrocytes previously observed.”

What the sources say

• Check pendingcites [14] Jabalera, Y., Garcia-Pinel, B., Ortiz, R., Iglesias, G., Cabeza, L., Prados, J., Jimenez-Lopez, C., and Melguizo, C. (2019). Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study. Pharmaceutics, 11. source

In the paper

“While LIPs and BMLs show a slight toxicity at very high doses (250 µg/mL) at 12 h of exposure, IMLs show a dramatic reduction of viability.”

In the paper

“In the context of the Oxa-BMNPs nanoassemblies, the addition of both a lipid shell and further pegylation not only improves the biocompatibility of the nanoassembly, but also the antiproliferative effect compared to that of soluble OXA.”

In the paper

“it can be observed that non-pegylated LIP present toxicity in the SW480, HCT15 and MC38 lines in a dose-dependent manner, being higher the toxicity in the MC38 cell line.”

In the paper

“while (ii) increase the intensity of the BMNPs response to an external magnetic field, thus increasing the efficiency of their magnetic guidance.”

In the paper

“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.”

What the sources say

• ?Not checked — no full text of the sourcecites [5] Peigneux, 2018, PH-Dependent Adsorption Release of Doxorubicin on MamC-Biomimetic Magnetite Nanoparticles, Langmuir source

In the paper

“In addition, a camptothecin nanoformulation achieved a pathologic complete response with only a grade 4 toxicity event in patients with advanced rectal cancer (phase Ib/II study) [26].”

What the sources say

• Check pendingcites [26] Sanoff, 2019, Phase I/II trial of nano-camptothecin CRLX101 with capecitabine and radiotherapy as neoadjuvant treatment for locally advanced rectal cancer, Nanomed. Nanotechnol. Biol. Med. source

In the paper

“In fact, a previous proof of concept showed that BMNPs were biocompatible and could be coupled with Oxaliplatin (Oxa) [14].”

What the sources say

• Check pendingcites [14] Jabalera, Y., Garcia-Pinel, B., Ortiz, R., Iglesias, G., Cabeza, L., Prados, J., Jimenez-Lopez, C., and Melguizo, C. (2019). Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study. Pharmaceutics, 11. source

In the paper

“Since BMNPs showed much better performance as Oxa carriers (detailed below), MNPs-bearing nanoformulations were not further used for the present study.”

In the paper

“However, as a drawback, there was a strong interaction of the nanoassemblies with the macrophages thus reducing the viability of these cells.”

What the sources say

• Check pendingcites [14] Jabalera, Y., Garcia-Pinel, B., Ortiz, R., Iglesias, G., Cabeza, L., Prados, J., Jimenez-Lopez, C., and Melguizo, C. (2019). Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study. Pharmaceutics, 11. source

In the paper

“However, their strong interaction with the macrophages revealed toxicity and possibility of aggregation.”

What the sources say

• Check pendingcites [14] Jabalera, Y., Garcia-Pinel, B., Ortiz, R., Iglesias, G., Cabeza, L., Prados, J., Jimenez-Lopez, C., and Melguizo, C. (2019). Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study. Pharmaceutics, 11. source

In the paper

“(1) a higher blocking temperature while being superparamagnetic at room temperature”

What the sources say

• ?Not checked — no full text of the sourcecites [5] Peigneux, 2018, PH-Dependent Adsorption Release of Doxorubicin on MamC-Biomimetic Magnetite Nanoparticles, Langmuir source

In the paper

“and it is also one of the first tryout for the local delivery of this drug”

In the paper

“In particular, Oxa induces peripheral sensory neurotoxicity [19] which may be the cause to discontinuation of drug treatment.”

What the sources say

• Check pendingcites [19] Bender, 2019, Adjuvant therapy for stages II and III colon cancer: Risk stratification, treatment duration, and future directions, Curr. Oncol. source

In the paper

“Harada et al. recently demonstrated a significant reduction of adverse effects (AEs) using a paclitaxel (PTX) nanoformulation (nab-PTX) in a phase I/II study of advanced non-small cell lung cancer (NSCLC) [24].”

What the sources say

• Check pendingcites [24] Harada, 2019, A phase I/II trial of weekly nab-paclitaxel for pretreated non-small-cell lung cancer patients without epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement, Asia Pac. J. Clin. Oncol. source

In the paper

“remaining attached to the nanoparticles and forming a nanocomposite (95 wt% magnetite + 5 wt% MamC)”

What the sources say

• ?Not checked — no full text of the sourcecites [5] Peigneux, 2018, PH-Dependent Adsorption Release of Doxorubicin on MamC-Biomimetic Magnetite Nanoparticles, Langmuir source

In the paper

“Fujiwara et al. showed a decrease (81.3%) of the peripheral sensory neuropathy with the use of polymeric micelles loaded with PTX (NK105) in patients with breast cancer (phase III) [25].”

What the sources say

• Not checked yetcites [25] Fujiwara, 2019, A multi-national, randomised, open-label, parallel, phase III non-inferiority study comparing NK105 and paclitaxel in metastatic or recurrent breast cancer patients, Br. J. Cancer source

In the paper

“Finally, NAPOLI-1 trial (phase III) assayed the administration of nal-IRI+5-FU/LV which increases the time without AEs ≥ 3 grade compared to 5-FU/LV in pancreatic cancer [27].”

What the sources say

• Check pendingcites [27] Pelzer, 2017, Quality-adjusted survival with combination nal-IRI+5-FU/LV vs 5-FU/LV alone in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy: A Q-TWiST analysis, Br. J. Cancer source

In the paper

“In fact, only magnetoliposomes containing Mms6-mediated BMNPs have been described so far, and their production is intended for magnetic resonance imaging [28,29,30].”

What the sources say

• Check pendingcites [28] Bakhshi, 2016, Manufacturing Man-Made Magnetosomes: High-Throughput In Situ Synthesis of Biomimetic Magnetite Loaded Nanovesicles, Macromol. Biosci. source
• Check pendingcites [29] Bain, 2015, In situ formation of magnetopolymersomes via electroporation for MRI, Sci. Rep. source
• Check pendingcites [30] Bain, 2019, A biomimetic magnetosome: Formation of iron oxide within carboxylic acid terminated polymersomes, Nanoscale source

In the paper

“The Oxa-BMNPs nanoassemblies used in the present study have been previously characterized in Jabalera et al. [14].”

What the sources say

• Check pendingcites [14] Jabalera, Y., Garcia-Pinel, B., Ortiz, R., Iglesias, G., Cabeza, L., Prados, J., Jimenez-Lopez, C., and Melguizo, C. (2019). Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study. Pharmaceutics, 11. source

In the paper

“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.”

In the paper

“All measurements, done in triplicate for each sample, were carried out at 25 °C using disposable plastic cuvettes.”

In the paper

“MamC controls magnetite nucleation and growth by both template and ionotropic effects [18]”

What the sources say

• ?Not checked — no full text of the sourcecites [18] Zarivach, 2017, Magnetite Nanoparticles Biomineralization in the Presence of the Magnetosome Membrane Protein MamC: Effect of Protein Aggregation and Protein Structure on Magnetite Formation, Cryst. Growth Des. source

In the paper

“it is well documented that SPIONs can accumulate in large amounts inside the cell, both in cancer cells and in normal cells [61,62].”

What the sources say

• ?Not checked — no full text of the sourcecites [61] Han, 2019, The synthesis and characterization of glutathione-modified superparamagnetic iron oxide nanoparticles and their distribution in rat brains after injection in substantia nigra, J. Mater. Sci. Mater. Med. source
• Check pendingcites [62] Iacovita, C., Florea, A., Dudric, R., Pall, E., Moldovan, A., Tetean, R., Stiufiuc, R., and Lucaciu, C. (2016). Small versus Large Iron Oxide Magnetic Nanoparticles: Hyperthermia and Cell Uptake Properties. Molecules, 21. source

In the paper

“However, BMLs have a biomimetic core with the MamC protein strongly adhered to its surface [5] while IMLs have a core with a free surface.”

What the sources say

• ?Not checked — no full text of the sourcecites [5] Peigneux, 2018, PH-Dependent Adsorption Release of Doxorubicin on MamC-Biomimetic Magnetite Nanoparticles, Langmuir source

In the paper

“It is widely reported in the literature that the accessibility of chelating agents that degrade iron oxide crystal depends on its functionalization and that this degradation begins first on surfaces where functionalization is less dense [53,54].”

What the sources say

• Not checked yetcites [53] Romero, 2015, Degradation of magnetic nanoparticles mimicking lysosomal conditions followed by {AC} susceptibility, Biomed. Tech.
• ?Not checked — no full text of the sourcecites [54] Lartigue, 2013, Biodegradation of iron oxide nanocubes: High-resolution in situ monitoring, ACS Nano source

In the paper

“the presence of the MamC protein on the surface of the core of BMLs not only slows down the degradation of the core, making the release of iron ions more gradual and therefore less toxic, but also increases their useful life allowing that they can be used for hyperthermia at longer exposure times without repeating their inoculation.”

In the paper

“The study of the biocompatibility in blood cells, cell internalization capability and cytotoxicity assays performed in the present work show that the enveloping in a lipid shell and the further pegylation improves the Oxa-BMNPs biocompatibility and cellular uptake without significantly reducing the Oxa cytotoxic activity in colon cancer cell lines.”

In the paper

“it is the first study in which nanoformulations are designed to locally release Oxa in which both a reduction of the IC50 compared to that for free Oxa, and an improvement of their biocompatibility and cellular uptake have been demonstrated.”

In the paper

“Our results are in agreement with the findings of other authors, who documented that pegylation reduced blood proteins binding [48] such as BSA and IgG [49] improving the dispersibility of the nanoparticles and reducing their interactions [50].”

What the sources say

• Check pendingcites [48] Stepien, 2018, Effect of Surface Chemistry and Associated Protein Corona on the Long-Term Biodegradation of Iron Oxide Nanoparticles In Vivo, ACS Appl. Mater. Interfaces source
• Check pendingcites [49] Zhang, 2019, MWCNT interactions with protein: Surface-induced changes in protein adsorption and the impact of protein corona on cellular uptake and cytotoxicity, Int. J. Nanomed. source
• Check pendingcites [50] Chiu, 2019, Effects of PEGylation on capture of dextran-coated magnetic nanoparticles in microcirculation, Int. J. Nanomed. source