Codelivery of resveratrol melatonin utilizing pH responsive sericin based nanocarriers inhibits the proliferation of breast cancer cell line at the different pH

Abstract

Protein-based nanocarriers have demonstrated good potential for cancer drug delivery. Silk sericin nano-particle is arguably one of the best in this field. In this study, we developed a surface charge reversal sericin-based nanocarrier to co-deliver resveratrol and melatonin (MR-SNC) to MCF-7 breast cancer cells as combination therapy. MR-SNC was fabricated with various sericin concentrations via flash-nanoprecipitation as a simple and reproducible method without complicated equipment. The nanoparticles were subsequently characterized for their size, charge, morphology and shape by dynamic light scattering (DLS) and scanning electron microscope (SEM). Nanocarriers chemical and conformational analysis were done by fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) respectively. In vitro drug release was determined at different pH values (7.45, 6.5 and 6). The cellular uptake and cytotoxicity were studies using breast cancer MCF-7 cells. MR-SNC fabricated with the lowest sericin concentration (0.1%), showed a desirable 127 nm size, with a net negative charge at physiological pH. Sericin structure was preserved entirely in the form of nano-particles. Among the three pH values we applied, the maximum in vitro drug release was at pH 6, 6.5, and 7.4, respectively. This pH dependency showed the charge reversal property of our smart nanocarrier via changing the surface charge from negative to positive in mildly acidic pH, destructing the electrostatic interactions between sericin surface amino acids. Cell viability studies demonstrated the significant toxicity of MR-SNC in MCF-7 cells at all pH values after 48 h, suggesting a synergistic effect of combination therapy with the two antioxidants. The efficient cellular uptake of MR-SNC, DNA fragmentation and chromatin condensation was found at pH 6. Nutshell, our result indicated proficient release of the entrapped drug combination from MR-SNC in an acidic environment leading to cell apoptosis. This work introduces a smart pH-responsive nano-platform for anti-breast cancer drug delivery.

Enhancing Cisplatin Efficacy with Low Toxicity in Solid Breast Cancer Cells Using pH-Charge-Reversal Sericin-Based Nanocarriers: Development, Characterization, and In Vitro Biological Assessment

“…Based on our findings, a 0.1% sericin concentration was selected for subsequent experiments. Our finding is in line with a previous study where the lowest concentration of sericin (0.1%) showed the appropriate nanoparticle size for SNCs (130 nm) and Cispt-SNCs (180 nm) with spherical morphology and the highest release efficiency of 69.82% at 34 h. Sericin, particularly at a low concentration of 0.1%, demonstrates excellent solubility, making it a highly promising candidate for antisolvent precipitation in nanoparticle production. This characteristic aligns with the properties of highly water-soluble proteins that have garnered significant interest for their application in antisolvent precipitation-based methods .…”

“…The utilization of circular dichroism (CD) as a sensitive biophysical technique allowed for the detailed examination of protein conformational changes in both this current research and our previous study . In this study, CD was used to investigate the secondary structure of sericin, following its formation of nanocapsules through the nanoprecipitation method.…”

“…In our prior research, we conducted tests on sericin at varying pH levels to evaluate drug release and cell viability. The findings revealed that the highest drug release from this nanocarrier transpires at pH 6, albeit significantly compromising cell viability . Hence, we selected pH 6 for cellular uptake studies.…”

“…To determine the optimal protein concentration, a previous study investigated different concentrations of sericin protein using the anti-solvent precipitation method . In our study, we built upon a prior investigation that explored various concentrations of sericin protein (0.1, 0.2, 0.3, 0.5, and 1% (w/v)) to determine the optimal formulation .…”

“…41 In our study, we built upon a prior investigation that explored various concentrations of sericin protein (0.1, 0.2, 0.3, 0.5, and 1% (w/v)) to determine the optimal formulation. 41 Our work aimed to contribute by selecting the 0.1% concentration, which was identified as the most suitable for preparing protein-based nanocapsules in terms of achieving small, spherical, and uniform particles with high cisplatin encapsulation. The use of flash nanoprecipitation, as adapted from Nelemans et al, serves as a robust and reproducible method that ensures the accessibility and practicality of nanocarrier fabrication.…”