Hyperthermia and Doxorubicin Release by Fol-LSMO Nanoparticles Induce Apoptosis and Autophagy in Breast Cancer Cells

Abstract

Background: Studies on the anticancer effects of lanthanum strontium manganese oxide (LSMO) nanoparticles (NPs)-mediated hyperthermia at cellular and molecular levels are scarce. Materials & methods: LSMO NPs conjugated with folic acid (Fol-LSMO NPs) were synthesized, followed by doxorubicin-loading (DoxFol-LSMO NPs), and their effects on breast cancer cells were investigated. Results: Hyperthermia (45°C) and combination treatments exhibited the highest (∼95%) anticancer activity with increased oxidative stress. The involvement of intrinsic mitochondria-mediated apoptotic pathway and induction of autophagy was noted. Cellular and molecular evidence confirmed the crosstalk between apoptosis and autophagy, involving Beclin1, Bcl2 and Caspase-3 genes with free reactive oxygen species presence. Conclusion: The study confirmed hyperthermia and doxorubicin release by Fol-LSMO NPs induces apoptosis and autophagy in breast cancer cells.

Graphical abstract

Keywords::

• apoptosis
• autophagy
• breast cancer
• combination therapy
• doxorubicin
• folic acid
• hyperthermia
• LSMO
• MDA-MB231 cells
• PEG

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/nnm-2022-0171

Author contributions

N Kulkarni-Dwivedi performed all the experiments. N Kulkarni-Dwivedi, SH Jadhav, RD Umrani and KM Paknikar conceptualized and designed the experiments and analyzed the data. N Kulkarni-Dwivedi, SH Jadhav and KM Paknikar wrote the manuscript. P Patel helped with Fourier transform IR and transmission electron microscopy analyses. BV Shravage assisted in autophagy-related studies.

Financial & competing Interests disclosure

The authors thank the Agharkar Research Institute (ARI; Pune, India), for research funds and the Indian Council of Medical Research (ICMR; New Delhi, India), for providing the research fellowship. This work was supported by funding obtained from the NBS-07 Project, funded by MACS-ARI, Pune, and Wistar Rat Sell, funded by the Animal House Facility, ARI, Pune. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Acknowledgments

The authors thank H Puntambekar (Agharkar Research Institute [ARI], Pune, India) for FTIR analysis, K Nilangekar (ARI, Pune) for technical help with Western blot analysis, A Dwivedi (ARI, Pune) for scanning electron microscope analysis and D Nayankumara (ARI, Pune) for technical support with handling the radiofrequency instrument. The authors also acknowledge R Hawaldar (Centre for Materials for Electronics Technology C-MET, Pune) for helping with the thermogravimetric analysis and R Venkata Naga Gundlooria (Council of Scientific and Industrial Research CSIR-National Chemical Laboratory NCL, Pune) for the FT-IR analysis.

Additional information

Funding

The authors thank the Agharkar Research Institute (ARI; Pune, India), for research funds and the Indian Council of Medical Research (ICMR; New Delhi, India), for providing the research fellowship. This work was supported by funding obtained from the NBS-07 Project, funded by MACS-ARI, Pune, and Wistar Rat Sell, funded by the Animal House Facility, ARI, Pune. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.