preprint · Research Square
Abstract Introduction: To overcome drug resistance and induce apoptosis in MCF-7/Adr human breast cancer cells which has a multidrug resistance, this study aims to develop a novel formulation of chitosan-sorafenib-conjugated FA nanoparticles (CsNPs-Sor-FA) for the efficient treatment of breast cancer. Methods The prepared formula was analyzed by using the FTIR, XRD, HRTEM, and UV-VIS spectrometers. A drug release experiment was performed in vitro, and the loading capacity and entrapment efficiency were estimated. The MTT assay was used to test for cytotoxicity. The nanoformula (CsNPs-Sor-FA) was tested as an anticancer treatment against MCF-7/adr cells by flow cytometry assay, cell cycle analysis, DNA fragmentation assay, real-time quantitative PCR (qRT-PCR), and western blot. Results We found that the CsNPs-Sor-FA formation had an average particle size of about 60 nm, an entrapment efficiency of 79 ± 2.9%, and a loading capacity 13.6 ± 1.2%. Around 90% of sorafenib was released from CsNPs-Sor after 120 hours, whereas CsNPs-Sor-FA nanoparticles exhibited an 88% sustained release pattern. The tested formulation of CsNPs-Sor-FA was not lethal to healthy lung cells. In addition, the morphological changes and DNA fragmentation results indicate that treatment with CsNPs-Sor-FA resulted in higher apoptosis data. Inhibition of cell cycle progression and inhibition of Nrf2 were also higher with CsNPs-Sor-FA treatment. Upregulation of apoptosis markers p53, caspase 9, caspase 8 and caspase 3, cytochrome c and TNFR was also observed; in contrast, expression of the anti-apoptotic marker Bcl-2 was reduced in the CsNPs-Sor-FA treated group compared to their individual treatments. Therefore, the nanoformula (CsNPs-Sor-FA) can be very useful for treating breast cancer. Conclusion Therefore, the present study has developed a nanoformula that shows promising antitumor activity against breast cancer cells and can improve survival rate of breast cancer patients.
This page summarises published work. The authoritative version sits with the publisher.
DOI: 10.21203/rs.3.rs-2860117/v1
Is something wrong with this record? Report it or request removal.
Discussion
Have you built on this work, tried to replicate it, or seen it applied in practice? Share what you know. Verified researchers and MARATTO™ domain experts can open a discussion, and any member can reply. Contributions are reviewed before they appear.
No discussion yet. Open the first thread.
New to MARATTO™? Create a free account.
