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. 2022 Jan 21;23(3):1200.
doi: 10.3390/ijms23031200.

Antibody Conjugated PLGA Nanocarriers and Superparmagnetic Nanoparticles for Targeted Delivery of Oxaliplatin to Cells from Colorectal Carcinoma

Alma Lucia Villela Zumaya  1 , Silvie Rimpelová  2 , Markéta Štějdířová  1 , Pavel Ulbrich  2 , Jarmila Vilčáková  3 , Fatima Hassouna  1
Affiliations

Antibody Conjugated PLGA Nanocarriers and Superparmagnetic Nanoparticles for Targeted Delivery of Oxaliplatin to Cells from Colorectal Carcinoma

Alma Lucia Villela Zumaya et al. Int J Mol Sci. .

Abstract

Anti-CD133 monoclonal antibody (Ab)-conjugated poly(lactide-co-glycolide) (PLGA) nanocarriers, for the targeted delivery of oxaliplatin (OXA) and superparamagnetic nanoparticles (IO-OA) to colorectal cancer cells (CaCo-2), were designed, synthesized, characterized, and evaluated in this study. The co-encapsulation of OXA and IO-OA was achieved in two types of polymeric carriers, namely, PLGA and poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) by double emulsion. PLGA_IO-OA_OXA and PEGylated PLGA_IO-OA_OXA nanoparticles displayed a comparable mean diameter of 207 ± 70 nm and 185 ± 119 nm, respectively. The concentration of the released OXA from the PEGylated PLGA_IO-OA_OXA increased very rapidly, reaching ~100% release after only 2 h, while the PLGA_IO-OA_OXA displayed a slower and sustained drug release. Therefore, for a controlled OXA release, non-PEGylated PLGA nanoparticles were more convenient. Interestingly, preservation of the superparamagnetic behavior of the IO-OA, without magnetic hysteresis all along the dissolution process, was observed. The non-PEGylated nanoparticles (PLGA_OXA, PLGA_IO-OA_OXA) were selected for the anti-CD133 Ab conjugation. The affinity of Ab-coated nanoparticles for CD133-positive cells was examined using fluorescence microscopy in CaCo-2 cells, which was followed by a viability assay.

Keywords: PLGA nanoparticles; antibody; colorectal cancer; drug delivery; iron oxide nanoparticles; oxaliplatin; targeted delivery.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Magnetic properties at room temperature (25 °C) of oleic acid-coated iron oxide nanoparticles (IO-OA) synthesized by co-precipitation. The measurement was performed in the magnetic field from −10 kOe to +10 kOe.
Figure 2
Figure 2
(A) 1H-NMR spectra of the PLGA, activated PLGA and diblock copolymer PLGA-PEG-NH2, and (B) FTIR spectra of PLGA, PEG diamine, and synthesized diblock copolymer PLGA-PEG-NH2.
Figure 3
Figure 3
TEM pictures of (A) PLGA nanoparticles; (B) oxaliplatin-loaded PLGA nanoparticles (PLGA_OXA); (C) oleic acid-coated iron oxide-loaded PLGA nanoparticles (PLGA_IO-OA); (D) PLGA-based multicomponent delivery systems (PLGA_IO-OA_OXA); (E) PEGylated PLGA nanoparticles; (F) oxaliplatin-loaded PEGylated PLGA nanoparticles (PEGylated PLGA_OXA); (G) oleic acid-coated iron oxide-loaded PEGylated PLGA nanoparticles (PEGylated PLGA_IO-OA) and (H) PEGylated PLGA-based multicomponent delivery systems (PEGylated PLGA_IO-OA_OXA).
Figure 4
Figure 4
Size and zeta potential measurement at day one and day 15 of (A) PLGA nanoparticles (PLGA), oxaliplatin-loaded PLGA nanoparticles (PLGA_OXA), oleic acid-coated iron oxide-loaded PLGA nanoparticles (PLGA_IO-OA), PLGA-based multicomponent delivery systems (PLGA_IO-OA_OXA) and their PEGylated analogs (B). The ratio of IO-OA:PLGA, OXA:PLGA, and their PEGylated analogs is equal to 1:10.
Figure 5
Figure 5
TG curves of pristine PLGA matrix, oxaliplatin (OXA), oxaliplatin-loaded PLGA nanoparticles (PLGA_OXA) and oxaliplatin-loaded PEGylated PLGA nanoparticles (PEGylated PLGA_OXA) under nitrogen atmosphere from room temperature (25 °C) to 800 °C at a heating rate of 10 °C·min−1.
Figure 6
Figure 6
Drug release profiles of oxaliplatin-loaded PLGA nanoparticles (PLGA_OXA), oxaliplatin-loaded PEGylated PLGA nanoparticles (PEGylated PLGA_OXA), PLGA-based multicomponent delivery systems (PLGA_IO-OA_OXA) and PEGylated PLGA-based multicomponent delivery systems (PEGylated PLGA_IO-OA_OXA) in PBS pH 7.4 at 37 °C.
Figure 7
Figure 7
Magnetization curves for the multicomponent PLGA based delivery system (PLGA_IO-OA_OXA) and its PEGylated analog (PEGylated PLGA_IO-OA_OXA) before and after dissolution tests measured at room temperature (25 °C) in the magnetic field from −10 kOe to +10 kOe.
Figure 8
Figure 8
Transmission electron microscopy images of the oxaliplatin-loaded PLGA nanoparticles, PLGA_OXA (A); anti-CD133 antibody conjugated oxaliplatin loaded PLGA nanoparticles, PLGA_OXA_Ab (B); multicomponent PLGA based delivery system, PLGA_IO-OA_OXA (C) and anti-CD133 antibody conjugated multicomponent PLGA-based delivery system, PLGA_IO-OA_OXA_Ab (D).
Figure 9
Figure 9
Fluorescence microscopy images of human cells derived from colorectal carcinoma (CaCo-2) stained with anti-CD133 antibody conjugated to Atto 565 for 30 min. Left—a bright-field image of the cells. Right—fluorescence emission of cells stained with anti-CD133-Atto 565. The scale bars correspond to 20 µm.
Figure 10
Figure 10
Fluorescence microscopy images of human cells derived from colorectal carcinoma (CaCo-2) treated with oxaliplatin-containing PLGA nanoparticles coated with anti-CD133 antibody conjugated to Alexa Fluor 488 (PLGA_OXA_Ab). The CaCo-2 cells were treated with 1.8–90 µg·mL−1 concentration of the PLGA_OXA_Ab for 30 min. Left—bright-field images of the cells. Right—fluorescence emission of cells treated with PLGA_OXA_Ab (false-colored based on the fluorescence emission intensity). The scale bars correspond to 20 µm.
Figure 11
Figure 11
Fluorescence microscopy images of human cells derived from colorectal carcinoma (CaCo-2) treated with oxaliplatin-containing PLGA nanoparticles coated with anti-CD133 antibody conjugated to Alexa Fluor 488 (PLGA_OXA_Ab) and co-stained with anti-CD133 Atto 565. The CaCo-2 cells were treated with 90 µg·mL−1 concentration of the PLGA_OXA_Ab for 30 min. From left: bright-field images of the cells; fluorescence emission of cells treated with PLGA_OXA_Ab; cells stained with anti-CD133-Atto 565; merge of the fluorescence images. The scale bars correspond to 20 µm.
Figure 12
Figure 12
Evaluation of the percentage of living cells in vitro after PLGA_OXA treatment. Human cells derived from colorectal carcinoma (CaCo-2) and human primary fibroblasts (MRC-5) were treated with PLGA_OXA for 72 h.
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References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Ferlay J., Ervik M., Lam F., Colombet M., Mery L., Piñeros M., Znaor A., Soerjomataram I., Bray F. Global Cancer Observatory: Cancer Today. International Agency for Research on Cancer; Lyon, France: 2020.
    1. Bishehsari F., Mahdavinia M., Vacca M., Malekzadeh R., Mariani-Costantini R. Epidemiological transition of colorectal cancer in developing countries: Environmental factors, molecular pathways, and opportunities for prevention. World J. Gastroenterol. 2014;20:6055–6072. doi: 10.3748/wjg.v20.i20.6055. - DOI - PMC - PubMed
    1. Arnold M., Abnet C.C., Neale R.E., Vignat J., Giovannucci E.L., McGlynn K.A., Bray F. Global Burden of 5 Major Types of Gastrointestinal Cancer. Gastroenterology. 2020;159:335–349. doi: 10.1053/j.gastro.2020.02.068. - DOI - PMC - PubMed
    1. Heidelberger C., Chaudhuri N.K., Danneberg P., Mooren D., Griesbach L., Duschinsky R., Schnitzer R.J., Pleven E., Scheiner J. Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature. 1957;179:663–666. doi: 10.1038/179663a0. - DOI - PubMed

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