A theragenerative bio-nanocomposite consisting of black phosphorus quantum dots for bone cancer therapy and regeneration

Ashkan Bigham; Ines Fasolino; Silvia Borsacchi; Carmen Valente; Lucia Calucci; Gabriele Turacchio; Marianna Pannico; Manuel Serrano-Ruiz; Luigi Ambrosio; Maria Grazia Raucci

doi:10.1016/j.bioactmat.2024.01.018

A theragenerative bio-nanocomposite consisting of black phosphorus quantum dots for bone cancer therapy and regeneration

Bioact Mater. 2024 Jan 24:35:99-121. doi: 10.1016/j.bioactmat.2024.01.018. eCollection 2024 May.

Authors

Ashkan Bigham^{1

2}, Ines Fasolino¹, Silvia Borsacchi^{3

4}, Carmen Valente⁵, Lucia Calucci^{3

4}, Gabriele Turacchio⁵, Marianna Pannico⁶, Manuel Serrano-Ruiz⁷, Luigi Ambrosio¹, Maria Grazia Raucci¹

Affiliations

¹ Institute of Polymers, Composites and Biomaterials, National Research Council of Italy (IPCB-CNR), Viale John Fitzgerald Kennedy 54, Mostra d'Oltremare Padiglione 20, 80125, Naples, Italy.
² Department of Chemical, Materials and Production Engineering, University of Naples Federico II, Piazzale V. Tecchio 80, 80125, Naples, Italy.
³ Institute for the Chemistry of OrganoMetallic Compounds-ICCOM, Italian National Research Council-CNR, via G. Moruzzi 1, 56124, Pisa, Italy.
⁴ Center for Instrument Sharing of the University of Pisa (CISUP), 56126, Pisa, Italy.
⁵ Institute of Experimental Endocrinology and Oncology "G. Salvatore" (IEOS), National Research Council (CNR), Via Pietro Castellino 111, 80131, Napoli, Italy.
⁶ Institute of Polymers, Composites, and Biomaterials, National Research Council of Italy (IPCB-CNR), Pozzuoli, Italy.
⁷ Institute for the Chemistry of OrganoMetallic Compounds-ICCOM, National Research Council-CNR, Sesto Fiorentino, Italy.

Abstract

Recently, the term theragenerative has been proposed for biomaterials capable of inducing therapeutic approaches followed by repairing/regenerating the tissue/organ. This study is focused on the design of a new theragenerative nanocomposite composed of an amphiphilic non-ionic surfactant (Pluronic F127), bioactive glass (BG), and black phosphorus (BP). The nanocomposite was prepared through a two-step synthetic strategy, including a microwave treatment that turned BP nanosheets (BPNS) into quantum dots (BPQDs) with 5 ± 2 nm dimensions in situ. The effects of surfactant and microwave treatment were assessed in vitro: the surfactant distributes the ions homogenously throughout the composite and the microwave treatment chemically stabilizes the composite. The presence of BP enhanced bioactivity and promoted calcium phosphate formation in simulated body fluid. The inherent anticancer activity of BP-containing nanocomposites was tested against osteosarcoma cells in vitro, finding that 150 μg mL^-1 was the lowest concentration which prevented the proliferation of SAOS-2 cells, while the counterpart without BP did not affect the cell growth rate. Moreover, the apoptosis pathways were evaluated and a mechanism of action was proposed. NIR irradiation was applied to induce further proliferation suppression on SAOS-2 cells through hyperthermia. The inhibitory effects of bare BP nanomaterials and nanocomposites on the migration and invasion of bone cancer, breast cancer, and prostate cancer cells were assessed in vitro to determine the anticancer potential of nanomaterials against primary and secondary bone cancers. The regenerative behavior of the nanocomposites was tested with healthy osteoblasts and human mesenchymal stem cells; the BPQDs-incorporated nanocomposite significantly promoted the proliferation of osteoblast cells and induced the osteogenic differentiation of stem cells. This study introduces a new multifunctional theragenerative platform with promising potential for simultaneous bone cancer therapy and regeneration.

Keywords: Bioactive glass; Black phosphorus; Bone cancer therapy; Microwave treatment; Tissue regeneration.