Lipid-nanoparticles-based co-delivery of black phosphorus quantum dots and melphalan by photothermal therapy combined with chemotherapy for retinoblastoma

Melphalan is an efficient chemotherapeutic agent for retinoblastoma (RB) in clinical practice. However, the problems of drug resistance and poor prognosis caused by long-term treatment of melphalan should not be ignored. At present, it is urgent to find a therapeutic strategy to enhance the curative effect to solve the need for clinical treatment of RB to protect eyesight. Herein, we propose an effective strategy to encapsulate melphalan and black phosphorus quantum dots (BPQDs) with high-biocompatibility liposomes for photothermal therapy (PTT) to enhance cell killing. BPQDs and melphalan were encapsulated using liposomes with a similar structure to the cell membrane, and a lipid nanoparticle with both photothermal and chemical inhibition effects was prepared. The obtained nanoparticle has a spherical shape (particle size range of 82–180 nm) and good stability (encapsulation efficiencies of melphalan of 40 % and BPQDs of 43.7 %). Its temperature increased to 65 °C within 10 min under a 2 W/cm2 laser at 808 nm, exerting photothermal and synergistic effects with melphalan to induce apoptosis of tumor cells. As expected, the prepared nanoparticle effectively inhibits tumor proliferation, upregulates the ki67 expression level, and has an excellent PTT effect on the orthotopic xenograft of WERI-RB-1 cells.