Doxorubicin-sanguinarine nanoparticles: formulation and evaluation of breast cancer cell apoptosis and cell cycle

Abstract

Background

Therapeutic resistance fails cancer treatment. Drug-nanoparticle combinations overcome resistance. Sanguinarine-conjugated nanoparticles may boost sanguinarine’s anticancer effects.

Methods

Sanguinarine, HPMC-NPs, and doxorubicin were tested on Adriamycin-resistant MCF-7/ADR breast cancer cells, parent-sensitive MCF-7, and MCR-5 normal cells (DX).

Results

Regular distribution, 156 nm diameter, <1 μm average size, 100% intensity—SN is therapeutic. Furthermore, the obtained NPs showed PDI = 0.145, zeta-potential=-37.6, and EE%=90.5%. DX sensitized MCF-7 cells (IC₅₀ = 1.4 μM) more than MCF-7/ADR cells (IC₅₀ = 27 μM) with RR = 19.3. SA and SN were more toxic to MCF-7/ADR cells (overexpressed with P-gp) than their sensitive parent MCF-7 cells (IC₅₀ = 4 μM, RR = 0.6 and 0.6 μM, RR = 0.7). MCR-5 normal lung cells were more resistant to SA (IC₅₀ = 7.2 μM) and SN (IC₅₀ = 1.6 μM) with a selection index > 2. Synergistic cytotoxic interactions reduced the IC₅₀ from 27 μM to 1.6 (CI = 0.1) and 0.9 (CI = 0.4) after DX and nontoxic dosages (IC₂₀) of SA and SN. DS and SN killed 27.1% and 39.4% more cells than DX (7.7%), SA (4.9%), SN (5.5%), or untreated control (0.3%). DS and DSN lowered CCND1 and survival in MCF-7/ADR cells while raising p21 and Casp3 gene and protein expression.

Conclusions

Cellular and molecular studies suggested adjuvant chemosensitizers SA and SN to reverse MDR in breast cancer cells.

Keywords:

• Sanguinarine
• doxorubicin, nanoparticles
• breast cancer
• multidrug resistance
• synergism

Disclosure statement

No potential conflict of interest was reported by the author(s). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Additional information

Funding

The authors extend their appreciation to the Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for funding this research work through the project number: [IFP22UQU4340212DSR168].