Quantitative Single‐Cell Comparison of Sensitization to Radiation and a Radiomimetic Drug for Diverse Gold Nanoparticle Coatings

• Published in: Small science 2024-09, Vol.4 (9), p.n/a
• Main Authors: Howard, Douglas, Turnbull, Tyron, Wilson, Puthenparampil, Paterson, David John, Milanova, Valentina, Thierry, Benjamin, Kempson, Ivan
• Format: Article
• Language: English
• Subjects: cancer; Cancer therapies; Cells; DNA damage; double‐strand breaks; Flow cytometry; Gold; nanomedicine; Nanoparticles; physical chemistry; Polyethylene glycol; Proteins; Quantitative analysis; Radiation therapy; radiotherapy; Surface chemistry; Toxicity; Tumors; X-rays; γH2AX
• ISSN: 2688-4046; 2688-4046
• DOI: 10.1002/smsc.202400053

Metal‐based nanoparticles (NPs) have entered clinical use for enhancing radiotherapy, but the underlying mechanisms remain ambiguous. Herein, single‐cell analysis of two cell lines in response to megavolt irradiation and a radiomimetic drug, neocarzinostatin (NCS) after coculture with gold NPs with different surface coatings, polyethylene glycol (AuPEG), PEG, and transferrin (AuT) or silica (AuSiO2), is reported. Different surface chemistry presents a major challenge for objective comparison between the biological impacts where major differences in cell‐uptake exist. AuSiO2 NPs are the most efficient for promoting radiosensitization despite being associated with cells 10 times less than the actively targeted AuT NPs. Conversely, for cells exposed to NCS, AuSiO2 NPs impede the radiomimetic action and promote cell survival. AuT NPs enhance death of cells in combination with NCS showing that NPs can sensitize against cytotoxic agents in addition to radiation. While NPs contribute to radiosensitization (or enhancing/impeding chemotherapeutic drug activity), due to cell and cell line heterogeneity, the ultimate radiosensitivity of a cell appears to be dominated by its inherent radiosensitivity and how this cell‐regulated response is manipulated by NPs. This is evidenced through comparison of radiobiological response of cells with equivalent NP association rather than equivalent coculture conditions. Nanoparticles (NPs) can sensitize cancer cells to both clinically relevant radiation energies and chemotherapy but the effects depend on cell and NP surface characteristics. When considering cells with identical quantities of internalized NPs, different surface chemistry results in different radiobiological effects. This shows that physical radiation dose deposition processes do not dominate radiosensitization and reveals new opportunities for sensitizing cancers.