MnI(CO)3-Prussian blue nanohybrids (MnI(CO)3@PBNPs) as red light-activatable platforms for synergic photo-activated chemotherapy and photodynamic therapy

Abstract

Prussian blue nanoparticles (PBNPs), an FDA-approved iron hexacyanoferrate framework, have emerged as multifunctional nanoplatforms for phototherapy owing to their biocompatibility, photostability, and strong red-to-NIR absorption. Building upon these advantages, we developed a red-light-activatable hybrid nanocomposite, Mn^I(CO)₃@PBNPs, by functionalizing PBNPs with a photoresponsive Mn^I–carbonyl complex. This nanoplatform integrates the photosensitizing nature of PBNPs with the photoinduced CO-releasing ability of Mn^I(CO)₃, achieving synergistic dual-mode therapy through photodynamic (PDT) and photoactivated chemotherapy (PACT) mechanisms. Under red-light irradiation (600–720 nm, 30 W), Mn^I(CO)₃@PBNPs simultaneously generated singlet oxygen (¹O₂) and cytotoxic CO (k_CO = 3.0 × 10⁻⁴ s⁻¹), leading to marked light-dependent cytotoxicity against MCF-7, MDA-MB-231, and Hep-G2 cells, with IC₅₀ values of 76, 82, and 92 µg mL⁻¹, respectively, while showing negligible dark toxicity (IC₅₀ > 200 µg mL⁻¹). Flow cytometry confirmed apoptosis as the primary mode of cell death. This work represents the first PBNP–Mn^I carbonyl hybrid achieving red-light-triggered PDT–PACT synergy, providing spatial and temporal therapeutic control. Owing to its biodegradability and tunable optical response, Mn^I(CO)₃@PBNPs hold strong potential for next-generation Prussian blue-based phototherapeutic nanomedicines.