A549 cell membrane-camouflaged Mn²⁺-doped Prussian blue/polydopamine nanoparticles for light-responsive chlorin e6...

A549 cell membrane-camouflaged Mn²⁺-doped Prussian blue/polydopamine-chlorin e6 nanoparticles (MnPB-PDA-Ce6@CCM) were developed as a biomimetic, light-responsive delivery system. MnPB nanoparticles were modified with polydopamine, conjugated with chlorin e6 (Ce6), and coated with A549 cell membranes by membrane extrusion. The formulation was optimized using a Box-Behnken design. Under the optimized conditions, MnPB-PDA-Ce6 exhibited a drug loading of 14.16 ± 0.42%, an encapsulation efficiency of 80.13 ± 0.25%, and a particle size of 38.25 ± 0.56 nm. Membrane coating increased the particle size to 50.26 ± 0.33 nm and produced a polydispersity index of 0.181 and a zeta potential of -25.97 ± 1.8 mV. Complementary physicochemical and protein analyses supported nanoparticle assembly and retention of A549 membrane-associated proteins. MnPB-PDA-Ce6@CCM showed enhanced Ce6 release under acidic conditions and 808 nm irradiation, photothermal heating under 808 nm irradiation, and reactive oxygen species generation under 660 nm irradiation. Compared with uncoated nanoparticles, MnPB-PDA-Ce6@CCM showed increased uptake by A549 cells and reduced uptake by RAW264.7 macrophages. Following laser irradiation, the coated formulation produced the greatest inhibition of A549 cells, with an IC₅₀ of 1.68 μg/mL. In rats, MnPB-PDA-Ce6@CCM altered the pharmacokinetic behavior of Ce6 and delayed its clearance. These findings support further evaluation of this biomimetic platform for light-responsive Ce6 delivery.