Fe(III)-coordination-driven fabrication of self-supplying oxygen and charge-convertible nanoplatform for enhanced photodynamic therapy of tumor

Abstract

The hypoxic microenvironment of tumors severely limits the effect of oxygen-dependent photodynamic therapy. Coordination-induced self-assemblies fabricate from metal ions and polymer ligands present potential advantages in catalytic reaction-mediated O2 production, high drug loading efficiency and system stability, as well as enhanced tumor targeting. In this work, self-supplying O2 and pH-induced charge-convertible nanoplatforms (termed as Sp-NPs) were fabricated through coordination-induced self-assembly of meso-tetrakis(4-carboxyphenyl)porphyrin (TCPP) modified and carboxylated pH sensitive polymeric ligand, poly (isobutylene-alt-maleic anhydride-conjugated-methoxy-poly(ethyleneglycol)-conjugated-imidazole-conjugated-ethylenediamine-grafted-TCPP) [PIMA-mPEG-API-EDA-TCPP], and ferric ions (Fe3+) for enhanced photodynamic therapy of cancer. The Sp-NPs displays uniform elliptic nanoparticles with size of around 90 nm and excellent stability in a variety of biomimetic biological media. Moreover, Sp-NPs bearing charge-convertible feature can flip the surface charge from negative to positive in the weakly acidic tumor extracellular condition, resulting in enhanced the cellular internalization. After entering more acidity tumor cells by endocytosis, Sp-NPs can be detonated to activate photosensitizers and release Fe3+ that can catalyze endogenous hydrogen peroxide (H2O2) to produce O2, leading to a prominent enhancement of fluorescence imaging and reactive oxygen species (ROS) generation in the tumor. Importantly, this nanoplatform exhibits a more potent cancer cell killing efficiency with good biosafety compared to that were treated with free TCPP. Therefore, incorporation self-oxygenation-boosted ROS strategy and pH-induced charge-convertible mechanism into this platform offered a great promise for cancer therapy.