Oxygen-Generating Organic/Inorganic Self-Assembled Nanocolloids for Tumor-Activated Dual-Model Imaging-Guided Photodynamic Therapy

Abstract

Tumor phototheranostics is usually compromised by the hypoxic tumor microenvironment and poor theranostic efficiency. The interplay between organic polymers and inorganic nanoparticles in novel nanocomposites has proven to be advantageous, overcoming previous limitations and harnessing their full potential through activation via the tumor microenvironment. This study successfully fabricated hypoxia-activated nanocolloids called HOISNDs through a process of self-assembly involving superparamagnetic iron oxide nanoparticles (SPIONs) and an organic polymer ligand called tetrakis(4-carboxyphenyl) porphyrin (TCPP)-engineered organic polymer ligand [methoxy poly(ethyleneglycol)-block-poly(dopamine-ethylenediamine-conjugated-4-nitrobenzyl chloroformate)-l-glutamate, mPEG-b-P(Dopa-EDA-co-NBCF)LG-TCPP)]. The SPIONs act as an oxygen generator to overcome the challenges posed by hypoxic tumors and enable the use of hypoxic-activatable MR/fluorescence dual-modal imaging-guided photodynamic therapy (PDT). The colloid stability of these HOISNDs proved to be exceptional in diverse biomimetic environments. Furthermore, they not only augment T2-weighted contrast capability as an MRI contrast agent but also function as an oxygen-producing device to amplify the generation and release of reactive oxygen species (ROS). The HOISNDs can significantly target to tumor sites through the enhanced permeability and retention (EPR) effect with prolonged blood circulation time and subsequently are effectively endocytosed into a hypoxic intracellular environment that “turn on” the imaging function and photodynamic activity. Moreover, HOISNDs possess the ability to effectively decompose naturally occurring H2O2 into oxygen (O2) within the tumor utilizing the Fenton reaction. This method can mitigate the impact of hypoxia on oxygen-dependent PDT. The outcomes of in vivo diagnostic and therapeutic evaluations indicated that HOISNDs are a highly promising tool for dual-model imaging-guided cancer theranosis by ameliorating hypoxic conditions and augmenting PDT efficiency.

Macromolecular Nano‐Assemblies for Enhancing the Effect of Oxygen‐Dependent Photodynamic Therapy Against Hypoxic Tumors

“…Upon irradiation, cerium oxide produces electron-hole pairs on the surface, which can react with O 2 and H 2 O to produce toxic superoxide anions and hydroxyl radicals for the enhancement of PDT. Iron oxide, [44] on the other hand, can catalyze the decomposition of H 2 O 2 via the Fenton reaction to generate O 2 and alleviate tumor hypoxia, while producing cytotoxic hydroxyl radicals for tumor elimination. Additionally, iron oxide can serve as a MRI contrast agent [31] Copyright 2023, Elsevier.…”

Type‐I Photodynamic Therapy Induced by Pt‐Coordination of Type‐II Photosensitizers into Supramolecular Complexes

“…Photodynamic therapy (PDT) has attracted great attention due to its noninvasive therapeutic modality [1–5] . In PDT, photosensitizers could absorb light to generate highly toxic reactive oxygen species (ROS) through photochemical reactions, which causes tumor cell apoptosis [6–10] . However, most PDT photosensitizers are strongly O 2 ‐tenstion dependent (Type‐II pathway), which greatly decreased their antitumor efficacy due to the inherent hypoxic tumor environment [11–14] .…”