Cancer-Cell-Activated Photodynamic Therapy Assisted by Cu(II)-Based Metal–Organic Framework

Abstract

Activation of photosensitizers (PSs) in targeted lesion and minimization of reactive oxygen species (ROS) depletion by endogenous antioxidants constitute promising approaches to perform highly effective image-guided photodynamic therapy (PDT) with minimal non-specific phototoxicity. Traditional strategies to fabricate controllable PS platforms rely on molecular design, which requires specific modification of each PS before PDT. Therefore, construction of a general tumor-responsive PDT platform with minimum ROS loss from endogenous antioxidant, typically glutathione (GSH), is highly desirable. Herein, MOF-199, a Cu(II) carboxylate-based metal−organic framework (MOF), is selected to serve as an inert carrier to load PSs with prohibited photosensitization during delivery. After cellular uptake, Cu (II) in the MOFs effectively scavenges endogenous GSH, concomitantly induces decomposition of MOF-199 to release the encapsulated PSs, and recovers their ROS generation. In vitro and in vivo experiments demonstrate highly effective cancer cell ablation and anticancer PDT with diminished normal cell phototoxicity. This strategy is generally applicable to PSs with both aggregation-induced emission and aggregation-caused quenching to implement activatable and enhanced image-guided PDT.

Reversing cold tumors to hot: An immunoadjuvant-functionalized metal-organic framework for multimodal imaging-guided synergistic photo-immunotherapy

“…In recent years, immunotherapy combined with nanotechnology, defined as nanoimmunotherapy, has shown promising performance for cancer therapy [ [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] ]. Among these therapeutics, metal-organic frameworks (MOFs), as a crystal material, has been widely studied in biomedical field [ [31] , [32] , [33] , [34] , [35] , [36] , [37] ]. MOFs of nanosized iron carboxylate, especially MIL101(Fe), have attracted considerable attention due to their excellent biocompatibility and biodegradability [ [38] , [39] , [40] ].…”

Aggregation‐Induced Emission: Recent Advances in Materials and Biomedical Applications

“…This allows large‐scale production of AIE NPs with desirable size by tuning the flow rate . Furthermore, several new methods have also been developed recently to encapsulate AIEgens into liposomes or metal organic frameworks (MOFs), which can further enhance their performance in biomedical research.…”

“…Meanwhile, as the concentration of H 2 O 2 in the normal tissues is extremely low, the ROS generation of F127‐TPETCF@MIL‐100 was kept at off state, eliminating the phototoxicity of the PSs. Furthermore, to realize precise PDT at targeted area and avoid the depletion of ROS in the tumour microenvironment, another promising strategy is reported recently (Figure a) . An AIE PS, TPAAQ, was loaded into a Cu II carboxylate‐based metal–organic framework (MOF‐199).…”

“…c) Viability of HepG2 cancer cells upon incubation with different reagents under white light or dark. d) CLSM images of EGFP‐kras V12 zebrafish larva at 7 day post‐fertilization bearing liver tumours with or without intravenous injection of TPAAQ@MOF‐199 NPs and light irradiation . Copyright 2019 American Chemical Society.…”

Recent Progress in the Development of Multifunctional Nanoplatform for Precise Tumor Phototherapy

“…Wang et al loaded the Ce6 into a copper-based metal organic framework (MOF) material (MOF-199) (Figure 10). [107] The photosensitizing activity of Ce6 was turned off in normal cells. MOF with redox active copper ions will react and consume GSH in tumor cells, leading to the dissociation of MOF and the release of Ce6.…”