A Metal‐Polyphenol‐Based Oxygen Economizer and Fenton Reaction Amplifier for Self‐Enhanced Synergistic Photothermal/Chemodynamic/Chemotherapy

Abstract

To overcome the limitations of doxorubicin (DOX) chemotherapy, nanomedicines that integrate additional photothermal therapy (PTT) and chemodynamic therapy (CDT) strategies are highlighted as promising alternatives for the treatment of malignant tumors. However, time-consuming preparation processes, biosafety concerns, and the bottlenecks of individual therapeutic modalities often limit the practical applications of this strategy. To address these issues, this work designs an oxygen economizer that additionally serves as a Fenton reaction amplifier through the simple assembly of epigallocatechin gallate (EGCG), pluronic F-127 (PF127), iron (III) ions, and doxorubicin (DOX) for the enhancement of synergistic PTT/CDT/chemotherapy. The resulting nanoformulation, EFPD, can target mitochondria and inhibit cell respiration to reduce O 2 consumption, thus boosting DOX-mediated H 2 O 2 generation for enhanced CDT and simultaneously improving hypoxia-limited DOX chemotherapy efficacy. Moreover, the coordination between EGCG and Fe 3+ provides EFPD with excellent photothermal conversion efficiencies (𝜼 = 34.7%) for PTT and photothermal-accelerated drug release. Experimental results indicate that EFPD-mediated synergistic enhancement of PTT/CDT/chemotherapy can achieve excellent therapeutic outcomes, including enhanced ablation of solid tumors, reduced metastasis and cardiotoxicity, and extended life spans.

Recent Advances of Metal–Polyphenol Coordination Polymers for Biomedical Applications

“…Polyphenols such as TA, EGCG, and Gossypol have strong antioxidant activity and the ability to scavenge reactive oxygen species (ROS). As the ideal nanotherapeutic drug, MPCPs have broad application prospects [ 80 , 81 , 82 ]. For example, Li et al constructed a nanosystem for targeted cancer therapy based on Sm III -EC NPs [ 21 ].…”

“…Usually, CDT was used to combinate with PTT and chemotherapy to achieve optimal tumor treatment. Shi et al designed a Fenton reaction amplifier through the assembly of EGCG, poloxamer F127, Fe 3+ , and DOX for the enhancement of synergistic PTT/CDT/chemotherapy [ 81 ]. The nanoplatforms inhibited cell respiration to reduce O 2 consumption, thus boosting H 2 O 2 generation for enhanced CDT and simultaneously improving DOX chemotherapy efficacy ( Figure 12 b).…”

“…( b ) Schematic of the proposed self-enhanced synergistic PTT/CDT/chemotherapy mechanism mediated by EFPD. Reprinted with permission from reference [ 81 ], copyright 2023 Wiley. ( c ) Schematic illustration of the constructed ssPPELap@Fe-TA for amplified ferroptosis-synergized immunotherapy.…”

Low‐Dose Cu Ions Assisted by Mild Thermal Stimulus Inducing Bacterial Cuproptosis‐Like Death for Antibiosis and Biointegration

“…It has been reported that NIR irradiation of photothermal sensors increases local temperature, which improves molecular motion, accelerating the release of doping ions. [21,33] Thus, Ca, P, and Cu ions released from PC with NIR irradiation for 10 min at 0.5 W cm −2 (labeled as PC-L) were additionally measured (Figure 1g). After 1 day of immersion, the released ions of Ca, P, and Cu are 10.1, 23.8, and 5.37 ppm, respectively, which are slightly higher than those from PC without irradiation, and they are still in the positive concentration ranges for tissue regeneration or antibiosis.…”