Nanoscale Covalent Organic Framework with Staggered Stacking of Phthalocyanines for Mitochondria-Targeted Photodynamic Therapy

Abstract

Phthalocyanine photosensitizers (PSs) have shown promise in fluorescence imaging and photodynamic therapy (PDT) of malignant tumors, but their practical application is limited by the aggregation-induced quenching (AIQ) and inherent photobleaching of PSs. Herein, we report the synthesis of a twodimensional nanoscale covalent organic framework (nCOF) with staggered (AB) stacking of zinc-phthalocyanines (ZnPc), ZnPc-PI, for fluorescence imaging and mitochondria-targeted PDT. ZnPc-PI isolates and confines ZnPc PSs in the rigid nCOF to reduce AIQ, improve photostability, enhance cellular uptake, and increase the level of reactive oxygen species (ROS) generation via mitochondrial targeting. ZnPc-PI shows efficient tumor accumulation, which allowed precise tumor imaging and nanoparticle tracking. With high cellular uptake and tumor accumulation, intrinsic mitochondrial targeting, and enhanced ROS generation, ZnPc-PI exhibits potent PDT efficacy with >95% tumor growth inhibition on two murine colon cancer models without causing side effects.

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

“…[77] More interestingly, some MNAs can exhibit intrinsic mitochondriatargeting properties without requiring any additional modifications. For example, Liu et al [78] developed zinc-phthalocyaninesbased MNAs with a staggered stacking structure, which was abundantly present in mitochondria after 10 h of incubation (Figure 7b). This study demonstrated a novel approach for the development of mitochondria-targeted MNAs by harnessing their inherent targeting capabilities and bypassing the necessity for complex modifications.…”

Ionic liquid-functionalized metal organic frameworks and their composite membranes for enhanced proton transport

“…17–21 These materials hold diverse potential applications in areas such as mixed gas separation, 22–24 toxic gas removal, 25–30 sensing, 31,32 light-mediated catalysis, 33–37 and therapy. 38–41 In particular, metal–organic frameworks (MOFs) with well-organized internal conduction pathways and a large pore volume containing numerous water molecules to facilitate the formation of hydrogen bond networks have been extensively investigated. 42,43 These efforts aim to identify promising proton conductors capable of elucidating fundamental conduction mechanisms and surpassing the conductivity achieved by Nafion.…”

[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis

“…The structures of some reported ferroptosis inducers. Some useful strategies have been proposed to promote cellular uptake and the accumulation of the drugs in organelles (particularly mitochondria) [18,19] and the synergistic operation between different therapeutic modalities, such as chemotherapy, chemodynamic therapy (CDT), and photodynamic therapy (PDT), by taking advantage of the chemical properties of the individual building blocks of nanomedicines. For example, Ke et al designed a cyclometallated Ir(III) complex featuring a −SH terminal as the cationic and photoactive building block [20].…”