Renal-Clearable Porphyrinic Metal–Organic Framework Nanodots for Enhanced Photodynamic Therapy

Abstract

Nanoscale porphyrinic metal–organic frameworks (NMOFs) have emerged as promising therapeutic platforms for the photodynamic therapy (PDT) of cancer in recent years. However, the relatively large sizes of current NMOFs ranging from tens to hundreds of nanometers usually lead to inefficient body clearance and unsatisfactory PDT effect, thus amplifying their long-term toxicity and restricting their further usage. To overcome these shortcomings, herein, ultrasmall porphyrinic metal–organic framework nanodots (MOF QDs) prepared from NMOFs are rationally synthesized via a facile method and used as renal-clearable nanoagents for the enhanced PDT of cancer. Compared with the precursor NMOFs, our well-prepared MOF QDs can generate 2-fold effective toxic reactive oxygen species (ROS) upon the same light irradiation and greatly decrease the inefficacy of PDT caused by the inefficient use of ROS generated from the interior of NMOFs. Meanwhile, the IC50 value of ultrasmall MOF QDs is nearly one-third that of NMOFs, and in vivo results demonstrate that our MOF QDs exhibit better PDT efficacy than NMOFs under the same treatment owing to their overcoming the limited ROS diffusion distance. Significantly, these ultrasmall MOF QDs show efficient tumor accumulation and rapid renal clearance in vivo, indicating their potential in biomedical utility. Last but not least, comprehensive investigations of long-term toxicity of these MOF QDs well demonstrate their overall safety. Therefore, this study will offer valuable insight into the development of safe and high-performance PDT nanoplatforms for further clinical translation.

Metal–Organic Frameworks for Biomedical Applications

“…a) Schematic illustration of the preparation of MOF QDs with high‐efficiency renal clearance for cancer therapy. Reproduced with permission 38. Copyright 2019, American Chemical Society.…”

“…For another instance, Wang et al reported ultrasmall porphyrin-MOF nanodots (MOF QDs) with high ROS generation, efficient tumor accumulation, and rapid renal clearance in vivo, which could enhance the therapeutic effect of PDT and overcome the long-term toxicity (Figure 5a). [38] The MOF QDs were prepared from PCN-224 NMOFs via a liquid phase exfoliation method, and then PEG was modified on the surface by the coordination interactions between Zr 6 and the carboxyl Small 2020, 16,1906846 Reproduced with permission. [35] Copyright 2015, American Chemical Society.…”

“…Reproduced with permission. [38] Copyright 2019, American Chemical Society. b) Schematic representation of Mn-ZrMOF NCs serving as nanoplatform for synergistic MDT and MTT of tumors.…”

Nanoscale Metal‐Organic Frameworks: Synthesis, Biocompatibility, Imaging Applications, and Thermal and Dynamic Therapy of Tumors

“…Then they once again constructed nanorod and nanorice‐like Hf‐based NMOFs with diameters of about 80 nm . Recently, Qu and co‐workers have utilized ultrasonic processor to acquire Zr‐based MOF nanodots, which effectively accelerated the accumulation in tumor, and also had the characteristics of kidney clearance owing to their ultra‐small size . Anyhow, the effect of these different morphologies on the interaction between cells and nanomaterials including endocytosis and accumulation at tumors, and the biocompatibility of materials are not clear yet, which are worth further investigation for synthesizing NMOFs with more biological application value.…”

“…Reproduced with permission. [74] Copyright 2019, American Chemical Society. e) Nanocubes of Zr-MOFs.…”