Transferrin-Conjugated Red Blood Cell Membrane-Coated Poly(lactic-co-glycolic acid) Nanoparticles for the Delivery of Doxorubicin and Methylene Blue

Herein, we demonstrate the preparation of transferrin (TF) receptor-targeted RBC membrane coated nanoparticles (NPs) to achieve chemotherapeutic and photodynamic effects. The TF conjugated RBC membranes were developed to incorporate doxorubicin (Dox) and methylene blue (MB) loaded PLGA NPs by the extrusion method to produce TF-DoxMB NPs. Characterizations revealed that the NPs were spherical in size (106 +/- 23 nm) with a zeta potential (zeta) of -12.6 mV. Coating of the TF conjugated membrane on the NP surface resulted in targeted delivery of the drugs to the TF receptor expressing cancer cells. Following this, exposure of the treated cells with red laser generated reactive oxygen species from photosensitizer MB. Targeted delivery of Dox and MB with subsequent laser irradiation selectively annihilated cancer cells. Viability assays and combination index (CI) analysis revealed synergistic action of the chemo- and photodynamic therapy. Interestingly, the antiproliferative effect of Dox and ROS produced due to photosensitization led to DNA damage mediated apoptosis in HeLa and MCF-7 cells. Targeting efficiency of the TF-DoxMB NPs was quite intriguing in tumor spheroids due to the synergistic action of Dox and MB.