Powerful Dual Metal–Organic Framework Heterointerface for Wound Healing

Infectious disease caused by bacteria has become a major threat to human health.¹ In recent years, photodynamic therapy (PDT) and photothermal therapy (PTT) have attracted increased attention as noninvasive therapeutic modalities. In PDT, photosensitizers can generate reactive oxygen species (ROS) to kill bacteria,² while in PTT, under light irradiation, the synthesized materials with high thermal conversion efficiency may convert electromagnetic wave energy to local heat to produce hyperthermia and subsequently kill inactivate bacteria.³ However, it is difficult for the single PDT or PTT strategy to achieve a satisfactory therapeutic effect due to either insufficient ROS content or temperature. In this issue of ACS Central Science, Luo and colleagues constructed a dual metal–organic framework (MOF) heterointerface with both PTT and PDT properties to achieve excellent antibacterial effects.⁴

Metal–organic frameworks, which are typically formed via coordination between metal ions and organic bridging ligands, have emerged as a promising platform in biomedical applications because of their flexible composition and structure, easy functionalization, good biocompatibility, and intrinsic biodegradability.⁵ Prussian blue (PB), a subclass of MOFs, has been previously approved by the US FDA for the treatment of radioactive exposure and has been extensively used in PTT on account of its good photothermal effect.⁶ Porphyrins can produce ROS and have been commonly used in PDT therapy.⁷ In the current study, Luo and colleagues synthesized PB nanoparticles as the core and constructed a porphyrins-doped UIO-66 MOF as the shell (Figure 1). This core–shell PB@MOF not only inherits the photothermal effect of PB but also adds the photodynamic merit of porphyrins, thereby exhibiting an excellent synergistic effect against bacterial infection.

Figure 1.

Schematic illustration of the core–shell structure of PB@MOF. PB is synthesized as a core. Due to the existence of defects in UIO-66, small porphyrin molecules are easily incorporated into the crystal structure of UIO-66, and the whole serves as a shell of PB@MOF.

Photocatalytic investigation reveals the significantly increased photocurrent density of core–shell PB@MOF compared with PB or MOF alone, which is attributed to the fact that the heterojunction between the outer MOF shell and the internal PB accelerates the separation efficiency of photogenerated electron–hole pairs. Additionally, PB@MOF exhibits an excellent PTT effect. The PTT effect is demonstrated by measured temperatures of PB@MOF in excess of 50 °C within 5 min under 808 nm NIR illumination, for 100 μg/mL PB@MOF solution. Notably, the PDT and PTT performance of this dual MOF is comparable with the state-of-the-art systems.⁸

Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) are the most common bacterial species in wound infections.^9,10 Luo and colleagues further assessed the antibacterial effect of PB@MOF against both S. aureus and E. coli under various light illuminations. The dual MOF structure kills more than 99% of both S. aureus and E. coli within 10 min of irradiation by 808 + 660 nm mixed light. Notably, the antibacterial property of PB@MOF is much better than those of PBS, PB, MOF, or PB@UIO-66, demonstrating its photothermal and photodynamic synergy. In addition, the PB@MOF is biocompatible and has low toxicity on cells.

With the excellent antibacterial performance in vitro, Luo and colleagues next assessed its extracorporeal wound healing using the S. aureus infection of a rat model. Impressively, in contrast to the control and 3 M groups, the PB@MOF with dual light illumination group shows the best wound-healing rate after 4, 8, and 14 days of treatment, and the wound is healed entirely in 14 days. Moreover, during the whole therapy, no unusual phenomena or injuries are observed in the main organs of rats, indicating the safety of PB@MOF.

This work offers a rational structural design of a dual metal–organic framework (PB@MOF) with both photothermal and photodynamic properties to heal the bacterial infection. In the future, many other aspects are waiting to be explored. For instance, the PB@MOF has a poor antibacterial effect under single illumination (808 nm NIR or 660 nm red light) for 10 min, which needs to be improved by employing more efficient photosensitizers. Moreover, the dual MOF shows continuous zirconium and iron ion release in the PBS solution. Although the zirconium and iron ions are nontoxic to cells under a certain dosage, the biosafety of artificial materials, especially long-term toxicity in vivo, must be investigated. Lastly, the PDT efficacy of PB@MOF originates from the doped porphyrin molecules and is determined by its doping amount. Unfortunately, the degree of defects in UIO-66 is generally low such that the doping amount of porphyrin molecules would not be very high. Therefore, it merits searching for other MOF shells, which directly possess PDT properties with no need for photosensitive dopants. Nevertheless, these limitations should not dampen the enthusiasm for the excellent work reported here, as it represents the first example of utilizing dual metal–organic frameworks with both photothermal and photodynamic properties for antibacterial effects and paves the way for future studies.