Nd³⁺‐Sensitized Upconversion Metal–Organic Frameworks for Mitochondria‐Targeted Amplified Photodynamic Therapy

Abstract

Herein, we report the design and synthesis of a mitochondria‐specific, 808 nm NIR light‐activated photodynamic therapy (PDT) system based on the combination of metal–organic frameworks (MOFs) and upconversion photochemistry with an organelle‐targeting strategy. The system was synthesized through the growth of a porphyrinic MOF on Nd3+‐sensitized upconversion nanoparticles to achieve Janus nanostructures with further asymmetric functionalization of the surface of the MOF domain. The PDT nanoplatform allows for photosensitizing with 808 nm NIR light, which could effectively avoid the laser‐irradiation‐induced overheating effect. Furthermore, mitochondria‐targeting could amplify PDT efficacy through the depolarization of the mitochondrial membrane and the initiation of intrinsic apoptotic pathway. This work sheds light on the hybrid engineering of MOFs to combat their current limitations for PDT.

Energy Transfer in Metal–Organic Frameworks and Its Applications

“…Recently, the controllable integration of nanoparticles (NPs) and MOFs to obtain composite NPs@MOFs that exhibit efficient EnT processes and enhanced performance has attracted significant attention from both academic and commercial entities. [ 104 ] Efforts are underway to better understand and document the related EnT process in this relatively unexplored field as most studies only focus on specific types of MOFs. The integration of UCNPs with fascinating nonlinear characteristics and MOFs represents a promising avenue of research that can be used to further expand the application of MOFs for biological upconversion processes.…”

Directional asymmetry over multiple length scales in reticular porous materials

“…Later, the same group functionalized the MOF surface of the system described above with triphenylphosphine, a ligand capable of targeting mitochondria, the cell responsible of initiating the apoptotic pathway. 86 This organelle-targeting strategy was able to amplify the photodynamic therapy efficacy through the in situ generation of ROS in mitochondria that activated the cancer cell death (Fig. 8d).…”

Light: A Magical Tool for Controlled Drug Delivery

“…For example, Janus nanostructures through the growth of porphyrinic MOF on Nd 3+ ‐sensitized UCNPs were successfully developed for mitochondria‐targeting, 808 nm NIR light‐activated photodynamic therapy. [ 65 ] The core–shell UCNP@porphyrinic MOFs for synergetic photodynamic/immuno‐chemotherapy against hypoxic cancer were also rationally designed. The heterostructure enabled NIR light‐activated cytotoxic ROS production for photodynamic therapy from MOF shells and hypoxia‐activated chemotherapy from the prodrug tirapazamine encapsulated in MOF nanopores.…”