A comparative study of sericin and gluten for magnetic nanoparticle-mediated drug delivery to breast cancer cell lines

Abstract

With breast cancer emerging as a pressing global health challenge, characterized by escalating incidence rates and geographical disparities, there is a critical need for innovative therapeutic strategies. This comprehensive research navigates the landscape of nanomedicine, specifically focusing on the potential of magnetic nanoparticles (MNPs), with magnetite (Fe₃O₄) taking center stage. MNPs, encapsulated in biocompatible polymers like silica known as magnetic silica nanoparticles (MSN), are augmented with phosphotungstate (PTA) for enhanced chemodynamic therapy (CDT). PTA is recognized for its dual role as a natural chelator and electron shuttle, expediting electron transfer from ferric (Fe³⁺) to ferrous (Fe²⁺) ions within nanoparticles. Additionally, protein-based charge-reversal nanocarriers like silk sericin and gluten are introduced to encapsulate (MSN-PTA) nanoparticles, offering a dynamic facet to drug delivery systems for potential revolutionization of breast cancer therapy. This study successfully formulates and characterizes protein-coated nanocapsules, specifically MSN-PTA-SER, and MSN-PTA-GLU, with optimal physicochemical attributes for drug delivery applications. The careful optimization of sericin and gluten concentrations results in finely tuned nanoparticles, showcasing uniform size, enhanced negative zeta potential, and remarkable stability. Various analyses, from Dynamic Light Scattering (DLS) and scanning electron microscopy (SEM) to transmission electron microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), X-Ray diffraction analysis (XRD), and Thermogravimetric analysis (TGA), provide insights into structural integrity and surface modifications. Vibrating Sample Magnetometer (VSM) analysis underscores superparamagnetic behavior, positioning these nanocapsules as promising candidates for targeted drug delivery. In vitro evaluations demonstrate dose-dependent inhibition of cell viability in MCF-7 and Zr-75-1 breast cancer cells, emphasizing the therapeutic potential of MSN-PTA-SER and MSN-PTA-GLU. The interplay of surface charge and pH-dependent cellular uptake highlights the robust stability and versatility of these nanocarriers in tumor microenvironment, paving the way for advancements in targeted drug delivery and personalized nanomedicine. This comparative analysis explores the suitability of silk sericin and gluten, unraveling a promising avenue for the development of advanced, targeted, and efficient breast cancer treatments.

Keywords: Breast cancer; Chemodynamic therapy; Drug delivery; Gluten; Magnetic nanoparticles; Nanomedicine; Protein-based nanocarriers; Silk sericin; Targeted therapy; pH-responsive.

Figure 1

General schematic of MSN-PTA-SER and MSN-PTA-GLU and their functional mechanism in targeted drug delivery.

Figure 2

Possible binding sites of sericin and gluten. (A) showcases the docking of sericin with PTA, highlighting possible binding sites indicated by boxes 1, 2, and 3, depicted in yellow, purple, and orange, respectively. (B–D) Similarly, purple represents the binding sites for the three subtypes of gluten.

Figure 3

Most important amino acids involved in interactions with PTA. The clusters with the highest stability in terms of energy and reproducibility, along with the critical amino acids engaged in interactions, have been illustrated. Sericin interactions (A–C) correspond to sericin gridboxes 1, 2, and 3, respectively. Similarly, gluten interactions (D–F) are linked to gliadin, glutenin high molecular weight, and glutenin low molecular weight, respectively.

Figure 4

DLS analysis of (A) Fe₃O₄, (B) MSN, (C) MSN-PTA, (D) MSN-PTA-SER, and (E) MSN-PTA-GLU. Zeta potential analysis of (F) Fe₃O₄, (G) MSN, (H) MSN-PTA, (I) MSN-PTA-SER, (J) MSN-PTA-GLU and (K) Overall comparison of zeta potential of mentioned nanoparticles with zeta of sericin and gluten alone.

Figure 5

SEM and TEM analyses with size distribution assessment performed using Image J. SEM images include: (A) Fe₃O₄, (B) MSN, (C) MSN-PTA, (D) MSN-PTA-SER, and (E) MSN-PTA-GLU, with detailed size distribution analysis using Image J. TEM images include: (F) MSN-PTA-SER, and (G) MSN-PTA-GLU.

Figure 6

The FT-IR spectra of Fe₃O₄, MSN, MSN-PTA, MSN-PTA-SER and MSN-PTA-GLU.

Figure 7

X-ray diffraction patterns of Fe₃O₄, MSN, MSN-PTA, MSN-PTA-SER and MSN-PTA-GLU.

Figure 8

The VSM examination of Fe₃O₄, MSN, MSN-PTA, MSN-PTA-SER and MSN-PTA-GLU.

Figure 9

The TGA examination of Fe₃O₄, MSN, MSN-PTA, MSN-PTA-SER and MSN-PTA-GLU.

Figure 10

The in vitro release of MSN-PTA at pH value of 7, 6.

Figure 11

Viability of MCF-7 cells at 24 h (A) and 48 h (B), and ZR-75–1 cells at 24 h (C) and 48 h (D) following exposure to different concentrations of MSN-PTA, MSN-PTA-SER, and MSN-PTA-GLU. Results represent the mean ± SD from three independent experiments, with statistical significance denoted by *P ≤ 0.05 compared to the respective controls.

Figure 12

Fluorescence microscopy revealed intracellular uptake of FITC-labeled MSN-PTA-SER and MSN-PTA-GLU at pH 6 in MCF-7 cells, alongside DAPI staining for visualizing cell nuclei, presented with a bar scale of 200 nm.