Shuttle-Shape Carrier-Free Platinum-Coordinated Nanoreactors with O₂ Self-Supply and ROS Augment for Enhanced Phototherapy of Hypoxic Tumor

Abstract

The synergistic nanotheranostics of reactive oxygen species (ROS) augment or phototherapy has been a promising method within synergistic oncotherapy. However, it is still hindered by sophisticated design and fabrication, lack of a multimodal synergistic effect, and hypoxia-associated poor photodynamic therapy (PDT) efficacy. Herein, a kind of porous shuttle-shape platinum (IV) methylene blue (Mb) coordination polymer nanotheranostics-loaded 10-hydroxycamptothecin (CPT) is fabricated to address the abovementioned limitations. Our nanoreactors possess spatiotemporally controlled O2 self-supply, self-sufficient singlet oxygen (1O2), and outstanding photothermal effect. Once they are taken up by tumor cells, nanoreactors as a cascade catalyst can efficiently catalyze degradation of the endogenous hydrogen peroxide (H2O2) into O2 to alleviate tumor hypoxia. The production of O2 can ensure enhanced PDT. Subsequently, under both stimuli of external red light irradiation and internal lysosomal acidity, nanoreactors can achieve the on-demand release of CPT to augment in situ mitochondrial ROS and highly efficient tumor ablation via phototherapy. Moreover, under the guidance of near-infrared (NIR) fluorescent imaging, our nanoreactors exhibit strongly synergistic potency for treatment of hypoxic tumors while reducing damages against normal tissues and organs. Collectively, shuttle-shape platinum-coordinated nanoreactors with augmented ROS capacity and enhanced phototherapy efficiency can be regarded as a novel tumor theranostic agent and further promote the research of synergistic oncotherapy.

Trojan-Horse Diameter-Reducible Nanotheranostics for Macroscopic/Microscopic Imaging-Monitored Chemo-Antiangiogenic Therapy

“…Therefore, the aforementioned experimental results combined with our previous report revealed that PFP possessed the metal− organic polycrystalline structures. 39 Further, the coordinationdriven supramolecular sequential co-assembly capacity of PFP was also estimated via determining the critical aggregation concentration (CAC) value as ca. 4.26 μg/mL (Figure S5).…”

“…37,38 To overcome the abovementioned issues, carrier-free metal−organic nanotheranostics such as metal−organic frameworks, coordination polymer nanotheranostics, and metal−organic supramolecular scaffolds have attracted extensive attention since the introduction of dynamic coordination interactions can remarkably enhance their structural integrity and stability. 39,40 Notably, such carrierfree metal−organic nanotheranostics possess on-demand drug release capacity, thereby reducing drug leakage during blood circulation. 41 In addition, the introduction of metal ions with excellent biosafety can expand application functions of nanosystems.…”

Advances in Antitumor Nano-Drug Delivery Systems of 10-Hydroxycamptothecin

“…Subsequently, stimulated by external NIR irradiation and internal lysosomal acidity, the NPs can achieve on-demand release of HCPT to increase in situ mitochondrial ROS and efficient tumor ablation by phototherapy. 272 …”

“…Once they are taken up by tumor cells, the NPs acting as cascade catalysts can effectively catalyze the degradation of endogenous hydrogen peroxide (H 2 O 2 ) into O 2 to alleviate tumor hypoxia. Subsequently, stimulated by external NIR irradiation and internal lysosomal acidity, the NPs can achieve on-demand release of HCPT to increase in situ mitochondrial ROS and efficient tumor ablation by phototherapy 272.…”

Binary dimeric prodrug nanoparticles for self-boosted drug release and synergistic chemo-photodynamic therapy

“…38–41 Upon light irradiation, the generated cytotoxic ROS by photosensitizers can oxidize adjacent lipids, amino acids, and nucleotides, and subsequently cause severe and irreversible damage to organelles, finally inducing cell necrosis or apoptosis. 42–45 The combination of chemotherapy and PDT can combat cancer through different mechanisms, thus showing great potency in maximizing the therapeutic efficacy. 46,47…”