ConspectusIn past decades, regular porous architectures have received a great amount of attention because of their versatile functions and applications derived from their efficient adsorption of various guests. However, most reported porous architectures exist only in the solid state. Therefore, their applications as biomaterials may face several challenges, such as phase separation, slow degradation, and long-term accumulation in the body. This Account summarizes our efforts with respect to the development and biomedical applications of water-soluble 3D diamondoid supramolecular organic frameworks (dSOFs), a family of supramolecular polymers that possess intrinsic regular nanoscale porosity.dSOFs have been constructed from tetratopic components and cucurbit[8]uril (CB[8]) through hydrophobically driven encapsulation by CB[8] for intermolecular dimers formed by peripheral aromatic subunits of the tetratopic components in water. All dSOFs exhibit porosity regularity or periodicity in aqueous solution, which is confirmed by solution-phase synchrotron SAXS and XRD experiments. Dynamic light scattering (DLS) reveals that their sizes range from 50 to 150 nm, depending on the concentrations of the components. As nonequilibrium supramolecular architectures, dSOFs can maintain their nanoscale sizes at micromolar concentrations for dozens of hours. Their diamondoid pores have aperture sizes ranging from 2.1 to 3.6 nm, whereas their water solubility and porosity regularity allow them to rapidly include discrete guests driven by ion-pair electrostatic attraction, hydrophobicity, or a combination of the two interactions. The guests may be small molecule or large macromolecular drugs, photodynamic agents (PDAs), or DNA.The rapid inclusion of bioactive guests into dSOFs has led to two important biofunctions. The first is to function as antidotes through including residual drugs. For heparins, the inclusion results in full neutralization of their anticoagulant activity. For clinically used porphyrin PDAs, the inclusion can alleviate their long-term posttreatment phototoxicity but does not reduce their photodynamic efficacy. The second is to function as in situ loading carriers for the intracellular delivery of antitumor drugs or DNA. Their nanoscale sizes bring out their ability to overcome the multidrug resistance of tumor cells, which leads to a remarkable enhancement of the bioactivity of the included drugs. By conjugating aldoxorubicin to tetrahedral components, albumin-mimicking prodrugs have also been constructed, which conspicuously improves the efficacy of aldoxorubicin toward multi-drug-resistant tumors through the delivery of the frameworks. As new supramolecular drugs and carriers, dSOFs are generally biocompatible. Thus, further efforts might lead to medical benefits in the future.

Supramolecular Organic Frameworks: Exploring Water-Soluble, Regular Nanopores for Biomedical Applications.

This review follows the research, development and clinical applications of the photosensitizer 5,10,15,20‐tetra(m‐hydroxyphenyl)chlorin (mTHPC, temoporfin) in photodynamic (cancer) therapy (PDT) and other medical applications. Temoporfin is the active substance in the medicinal product Foscan® authorized in the EU for the palliative treatment of head and neck cancer. Chemistry, biochemistry and pharmacology, as well as clinical and other applications of temoporfin are addressed, including the extensive work that has been done on formulation development including liposomal formulations. The literature has been covered from 2009 to early 2022, thereby connecting it to the previous extensive review on this photosensitizer published in this journal [Senge, M. O. and J. C. Brandt (2011) Photochem. Photobiol. 87, 1240–1296] which followed its way from initial development to approval and clinical application.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/php.13730

The Photosensitizer Temoporfin (mTHPC) – Chemical, Pre‐clinical and Clinical Developments in the Last Decade † ‡

Excess bilirubin accumulates in the bodies of patients suffering from acute liver failure (ALF) to cause much irreversible damage and bring about serious clinical symptoms such as kernicterus, hepatic coma, or even death. Hemoperfusion is a widely used method for removing bilirubin from the blood, but clinically used adsorbents have unsatisfactory adsorption capacity and kinetics. In this study, we prepared four supramolecular organic framework microcrystals SOF-1-4 via slow evaporation of their aqueous solutions under infrared light. SOF-1-4 possess good regularity and excellent stability. We demonstrate that all the four SOFs could serve as adsorbents for bilirubin with fast adsorption kinetics within 20 min and ultrahigh adsorption capacity of 609.1 mg g-1, driven by electrostatic interaction and hydrophobicity. The superior adsorption performance of the SOFs outperformed most of the reported bilirubin adsorbents. Remarkably, SOF-3 could remove about 90% of bilirubin in the presence of 40 g L-1 BSA with a minimal loss of albumin and was thus further processed to a bead-shaped composite with a diameter of 2 mm with poly(ether sulfone) (PES). This PES-loaded SOF could efficiently adsorb bilirubin to the normal level from human plasma with an adsorption equilibrium concentration of 7.8 mg L-1 in 6 h through a dynamic hemoperfusion process. This work provides a new vitality for the development of novel bilirubin adsorbents for hemoperfusion therapy.

Supramolecular Organic Frameworks as Adsorbents for Efficient Removal of Excess Bilirubin in Hemoperfusion.

Nano-ROS-generating approaches to cancer dynamic therapy: Lessons from Nanoparticles

Nanotechnology and photodynamic therapy from a clinical perspective

Supramolecular organic frameworks improve the safety of clinically used porphyrin photodynamic agents and maintain their antitumor efficacy.

Water-soluble three-dimensional supramolecular-organic frameworks (SOFs) and temoporfin (mTHPC) are discovered to form uniform self-assembled nanoparticles. These nanoparticles demonstrate an improved 1O2 generation efficiency due to the reduced aggregation-caused quenching effect. SOFs and self-assembled nanoparticles are biocompatible. Self-assembled nanoparticles display an improved photo cytotoxicity toward four types of human cancer cells. The tumor model in mice shows that self-assembled nanoparticles could efficiently suppress tumor growth in vivo.

Self-assembled nanoparticles based on supramolecular-organic frameworks and temoporfin for an enhanced photodynamic therapy in vitro and in vivo.

Broad-spectrum agents for the reversal of residual curarization induced by neuromuscular blocking agents are of great significance. Here, we report a highly water-soluble cucurbit[8]uril (CB[8]) derivative as a broad-spectrum neuromuscular block reversal agent induced by both benzylisquinolinium and aminosteroid neuromuscular block agents by the supramolecular sequestration strategy. The UV/Vis competition titration assays suggest the high binding affinity of the CB[8] derivative toward both benzylisquinolinium-type cisatracurium besylate and aminosteroid-type rocuronium, vecuronium, and pancuronium, at the level of 107 M-1. In vivo studies demonstrate that the administration of the CB[8] derivative could significantly accelerate the recovery time compared to the placebo or neostigmine groups. The reversal activity of the CB[8] derivative is comparable to or higher than that of clinically approved sugammadex. Acute toxicity evaluations reveal that the CB[8]-derivative displays outstanding biocompatibility, with the maximum tolerance dose as high as 960 mg kg-1.

Da Ma

Papers

Supramolecular organic frameworks improve the safety of clinically used porphyrin photodynamic agents and maintain their antitumor efficacy.

Self-assembled nanoparticles based on supramolecular-organic frameworks and temoporfin for an enhanced photodynamic therapy in vitro and in vivo.

Highly Water-Soluble Cucurbit[8]uril Derivative as a Broad-Spectrum Neuromuscular Block Reversal Agent.

An All-in-One Zeolite@Ru-Al2O3 Nanoplatform towards Highly Efficient, Anticoking, and Recyclable Hydrocarbon Cracking Catalysis

Porous organic polymer overcomes the post-treatment phototoxicity of photodynamic agents and maintains their antitumor efficiency.