Tangential Flow Ultrafiltration Allows Purification and Concentration of Lauric Acid-/Albumin-Coated Particles for Improved Magnetic Treatment

Zaloga, Jan; Stapf, Marcus; Nowak, Johannes; Pöttler, Marina; Friedrich, Ralf P.; Tietze, Rainer; Lyer, Stefan; Lee, Geoffrey; Odenbach, Stefan; Hilger, Ingrid

doi:10.3390/ijms160819291

Cited by 25 publications

(17 citation statements)

References 37 publications

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“…Excess albumin was then removed from solution using a previously reported tangential ultrafiltration method. 24 All suspensions were sterilized using a 0.22 µm syringe filter. The total iron content was determined using MP-AES.…”

Section: Materials and Methods Materialsmentioning

confidence: 99%

Selection of potential iron oxide nanoparticles for breast cancer treatment based on in vitro cytotoxicity and cellular uptake

Poller¹,

Zaloga²,

Schreiber³

et al. 2017

IJN

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Superparamagnetic iron oxide nanoparticles (SPIONs) are promising tools for the treatment of different diseases. Their magnetic properties enable therapies involving magnetic drug targeting (MDT), hyperthermia or imaging. Depending on the intended treatment, specific characteristics of SPIONs are required. While particles used for imaging should circulate for extended periods of time in the vascular system, SPIONs intended for MDT or hyperthermia should be accumulated in the target area to come into close proximity of, or to be incorporated into, specific tumor cells. In this study, we determined the impact of several accurately characterized SPION types varying in size, zeta potential and surface coating on various human breast cancer cell lines and endothelial cells to identify the most suitable particle for future breast cancer therapy. We analyzed cellular SPION uptake, magnetic properties, cell proliferation and toxicity using atomic emission spectroscopy, magnetic susceptometry, flow cytometry and microscopy. The results demonstrated that treatment with dextran-coated SPIONs (SPION Dex ) and lauric acid-coated SPIONs (SPION LA ) with an additional protein corona formed by human serum albumin (SPION LA-HSA ) resulted in very moderate particle uptake and low cytotoxicity, whereas SPION LA had in part much stronger effects on cellular uptake and cellular toxicity. In summary, our data show significant dose-dependent and particle type-related response differences between various breast cancer and endothelial cells, indicating the utility of these particle types for distinct medical applications.

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Section: Materials and Methods Materialsmentioning

confidence: 99%

Selection of potential iron oxide nanoparticles for breast cancer treatment based on in vitro cytotoxicity and cellular uptake

Poller¹,

Zaloga²,

Schreiber³

et al. 2017

IJN

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“…[3][4][5][6][7] Moreover, MNP can be heated in an alternating magnetic field, allowing a localized sensitization or destruction of tumor cells or tumor tissue by hyperthermal or even thermoablative temperatures. [8][9][10][11] For magnetic heating purposes, iron oxide MNP with a clustered magnetite or maghemite core and an appropriate coating (polyethylene glycol [PEG], dextran, dimercaptosuccinic acid [DMSA], etc) have been shown to exhibit good heating capabilities and biocompatibility. 10,[12][13][14][15][16] One chemotherapeutic drug that can effectively be coupled to MNP is methotrexate (MTX).…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia

Stapf¹,

Pömpner²,

Teichgräber³

et al. 2016

IJN

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Today, the therapeutic efficacy of cancer is restricted by the heterogeneity of the response of tumor cells to chemotherapeutic drugs. Since those therapies are also associated with severe side effects in nontarget organs, the application of drugs in combination with nanocarriers for targeted therapy has been suggested. Here, we sought to assess whether the coupling of methotrexate (MTX) to magnetic nanoparticles (MNP) could serve as a valuable tool to circumvent the heterogeneity of tumor cell response to MTX by the combined treatment with hyperthermia. To this end, we investigated five breast cancer cell lines of different origin and with different mutational statuses, as well as a bladder cancer cell line in terms of their response to exposure to MTX as a free drug or after its coupling to MNP as well as in presence/absence of hyperthermia. We also assessed whether the effects could be connected to the cell line-specific expression of proteins related to the uptake and efflux of MTX and MNP. Our results revealed a very heterogeneous and cell line-dependent response to an exposure with MTX-coupled MNP (MTX–MNP), which was almost comparable to the efficacy of free MTX in the same cell line. Moreover, a cell line-specific and preferential uptake of MTX–MNP compared with MNP alone was found (probably by receptor-mediated endocytosis), agreeing with the observed cytotoxic effects. Opposed to this, the expression pattern of several cell membrane transport proteins noted for MTX uptake and efflux was only by tendency in agreement with the cellular toxicity of MTX–MNP in different cell lines. Higher cytotoxic effects were achieved by exposing cells to a combination of MTX–MNP and hyperthermal treatment, compared with MTX or thermo-therapy alone. However, the heterogeneity in the response of the tumor cell lines to MTX could not be completely abolished – even after its combination with MNP and/or hyperthermia – and the application of higher thermal dosages might be necessary.

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“…As one of the main membrane filtration techniques, TFF (or cross flow filtration) has been used for decades to purify and concentrate biotherapeutics in the pharmaceutical industry . Equipped with filters with different MWCO, TFF also enables purification, size selection, and concentration of nanoparticles.…”

Section: Resultsmentioning

confidence: 99%

In Vitro Evaluation of Anti‐Aggregation and Degradation Behavior of PEGylated Polymeric Nanogels under In Vivo Like Conditions

Chen

Dakwar

Braeckmans

et al. 2017

Macromolecular Bioscience

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The in vivo stability and biodegradability of nanocarriers crucially determine therapeutic efficacy as well as safety when used for drug delivery. This study aims to evaluate optimized in vitro techniques predictive for in vivo nanocarrier behavior. Polymeric biodegradable nanogels based on hydroxyethyl methacrylamide‐oligoglycolates‐derivatized poly(hydroxyethyl methacrylamide‐co‐N‐(2‐azidoethyl)methacrylamide) and with various degrees of PEGylation and crosslinking densities are prepared. Three techniques are chosen and refined for specific in vitro evaluation of the nanocarrier performance: (1) fluorescence single particle tracking (fSPT) to study the stability of nanogels in human plasma, (2) tangential flow filtration (TFF) to study the degradation and filtration of nanogel degradation products, and (3) fluorescence fluctuation spectroscopy (FFS) to evaluate and compare the degradation behavior of nanogels in buffer and plasma. fSPT results demonstrate that nanogels with highest PEGylation content show the least aggregation. The TFF results reveal that nanogels with higher crosslink density have slower degradation and removal by filtration. FFS results indicate a similar degradation behavior in human plasma as compared to that in phosphate buffered saline. In conclusion, three methods can be used to compare and select the optimal nanogel composition, and these methods hold potential to predict the in vivo performance of nanocarriers.

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Tangential Flow Ultrafiltration Allows Purification and Concentration of Lauric Acid-/Albumin-Coated Particles for Improved Magnetic Treatment

Cited by 25 publications

References 37 publications

Selection of potential iron oxide nanoparticles for breast cancer treatment based on in vitro cytotoxicity and cellular uptake

Selection of potential iron oxide nanoparticles for breast cancer treatment based on in vitro cytotoxicity and cellular uptake

Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia

In Vitro Evaluation of Anti‐Aggregation and Degradation Behavior of PEGylated Polymeric Nanogels under In Vivo Like Conditions

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