A multifunctional NIR responsive upconversion porphyrin nanoprobe for Fenton/FRET induced ROS amplification and targeted drug delivery

Abstract

The tumor microenvironment (TME) is marked by hyperactivated signaling molecules, acidic pH, elevated GSH levels, immune evasion, and hypoxia causing therapeutic resistance. Monotherapy is restricted by various constraints in the intracellular system which calls for combinational technologies to enhance individual effects. In the present work, we have constructed a core-shell upconversion porphyrin metal organic framework (UCNP@Cu-TCPP MOF) nano drug delivery system with an in-built combinational, photodynamic (PDT) and chemodynamic therapy (CDT) under 980 nm light irradiation. A rapid microwave method was applied for synthesis of NaYF₄: Yb,Er upconversion nanoparticles (UCNPs), and the shelling of porphyrin MOF was achieved through a single step in-situ method. Cu²⁺ is reduced to Cu⁺ by GSH in the TME which is reacted upon by H₂O₂ via Fenton reaction to produce reactive oxygen species (ROS) mainly (^•OH) leading to GSH depletion and oxygen elevation in the cells. Further, NIR (near IR) light conversion through FRET mechanism between UCNP and Cu-TCPP MOF amplified the production of (¹O₂), confirmed with EPR and UV-visible spectroscopy. The porous structure of MOF allows ample loading of anticancer drug, Doxorubicin (∼20 %) and folic acid, facilitating targeted delivery. The pH-responsive activity of UCNP@Cu-TCPP@FA@DOX with excellent water dispersibility, stability, and biocompatibility, shows cancer cell apoptosis up to 80 %. The synthesized nano drug delivery system harnesses the photosensitizing properties of porphyrin, along with copper ions induced chemodynamic effect and targeted chemotherapy, promising a multifunctional approach towards cancer treatment.