Iron doped carbon dots based nanohybrids as a tetramodal imaging agent for gene delivery promotion and photothermal-chemodynamic cancer synergistic theranostics

Abstract Nonviral gene delivery vectors for cancer therapy still confronts great challenges as their low transfection efficiency, vague tracing and poor therapeutic effects. Recently, organic–inorganic nanohybrids show complementary and synergistic effects in nano-scaled delivery system, inspiring their applications in gene delivery exploration. A liposomal carbon dots nanohybrids system (PEG-RLS/Fe@CDs) have been fabricated, which was composed of iron-doped carbon dots (Fe@CDs) derived from iron (II) phthalocyanine and amphiphilic lipopeptide assemblies (DSPE-mPEG2000/RLS). With its excellent photothermal conversion capability (η = 63.4%), gene transfection efficiency was increased by 3.5-fold in 4T1 tumor cell and 2-fold in animal model. Introduction of Fe@CDs in the nanohybrids could also serve as a tetramodal contrast agent for fluorescence/photoacoustic/photothermal/magnetic resonance imaging, showing up to 3 orders of magnitude enhancement in photoacoustic signal, as well as 16 °C temperature increasement after 5 min irradiation inside tumor tissue. Furthermore, both in vitro and in vivo studies confirmed the bioactivity of PEG-RLS/Fe@CDs as nanozyme for photothermal and chemodynamic synergistic therapy, leading to a noticeable inhibited tumor growth with 80% survival for at least 50 days in a breast tumor model. These revealed the PEG-RLS/Fe@CDs is a promising candidate platform for improving gene therapy by transfection enhancement, real-time tracing and tumor synergistic destruction.