Design of a Metallacycle‐Based Supramolecular Photosensitizer for In Vivo Image‐Guided Photodynamic Inactivation of Bacteria

Abstract

Bacterial infection is one of the greatest threats to public health. In vivo real-time monitoring and effective treatment of infected sites through non-invasive techniques, remain ac hallenge.H erein, we designed aP t II metallacyclebased supramolecular photosensitizer through the host-guest interaction between apillar[5]arene-modified metallacycle and 1-butyl-4-[4-(diphenylamino)styryl]pyridinium. Leveraging the aggregation-induced emission supramolecular photosensitizer,w ei mproved fluorescence performance and antimicrobial photodynamic inactivation. In vivo studies revealed that it displayed precise fluorescence trackingo fS .a ureus-infected sites,a nd in situ performed image-guided efficient PDI of S. aureus without noticeable side effects.T hese results demonstrated that metallacycle combined with host-guest chemistry could provideaparadigm for the development of powerful photosensitizers for biomedicine.

PEG: Will It Come Back to You? Polyethelyne Glycol Immunogenicity, COVID Vaccines, and the Case for New PEG Derivatives and Alternatives

“…Polymer-drug conjugates have since gradually increased in their clinical application, now with more than 29 marketed products that vary widely in polymer architecture (linear and branched), molecular weight (0.3–60 kDa per polymer), and degree of conjugation (1–69-82 per drug) and nearly all of which employ the synthetic polymer, PEG, a polyether typically produced by the ring-opening polymerization of ethylene glycol ( Alconcel et al, 2011 ; Ekladious et al, 2019 ; Xu et al, 2022 ). In addition to the diversity of their appended polymers, these therapeutics also vary widely in their drug partner, ranging from: 1) peptides (e.g.…”

“…PEG’s remarkable hydrophilicity, flexibility, inertness, and relative biocompatibility have found the polymer numerous uses beyond modulating drug circulation or activity and today it can be found near ubiquitously in both consumer products such as detergents, cosmetics, and car wax, as well as in industrial applications including electroplating, historical artifact preservation, and molded product production ( Harris, 1992 ; Prime and Whitesides, 1993 ; Harris and Chess, 2003 ; Li et al, 2005 ; Jokerst et al, 2011 ). PEGylating has also been used to improve stability of contrast agents for in vivo fluorescence imaging, photodynamic therapy, and sonodynamic therapy ( Ding et al, 2018 ; Chen et al, 2021 ; Xu et al, 2022 ). Given PEG’s near exclusive utilization in polymer-drug conjugates, our rapidly increasing consumer use of the compound, and recent, prevalent, and systemic exposure to PEG in the form of mRNA vaccines and boosters for SARS-CoV-2 (currently >0.5 bn doses ( C ovid-data-tracker, 2022 ) in the United States) ( Polack et al, 2020 ; Baden et al, 2021 ), several obvious questions arise with relevance to both public awareness and public health: Is PEG immunogenetic?…”

“…For example, the molar concentration of PEG-proteins in circulation is typically lower than that of PEG-liposomes ( Grenier et al, 2018 ) at therapeutic dosing levels; thus, nanoparticles are thought to be less vulnerable to anti-PEG antibody-associated clearance than proteins. Indeed, prior studies show that strong ABC is observed when the number of antibodies in circulation exceeds the number of PEGylated compounds ( Xu et al, 2022 ). This trend holds across most PEGylated compounds including proteins, liposomes, micelles, and polymeric nanoparticles and agrees with previous studies showing that three anti-PEG antibodies per PEGylated protein or about 10 anti-PEG antibodies per pegylated liposome are required for ABC ( Shiraishi et al, 2016 ; McSweeney et al, 2018 ; Chang et al, 2019 ).…”

“…PEG-IFNα) may be susceptible to polymer-specific ABC whereas the estimated threshold concentration of anti-PEG antibodies needed to accelerate the clearance of nucleic acid drug carriers ( e.g. Patrisan) overwhelmingly exceed those observed in patient blood ( Xu et al, 2022 ).…”

A NIR-emissive probe with a remarkable Stokes shift for CO-releasing molecule-3 detection in cells andin vivo

“…In order to detect CORM-3 in various biological systems, activatable fluorescent probes have unique advantages, such as simplicity of operation, excellent sensitivity, good specificity, and real-time imaging abilities. [18][19][20][21][22][23][24] At present, some probes for the selective detection of CORM-3 based on small molecule organic fluorophores have been established. [25][26][27][28][29] Emission from most CORM-3 fluorescent probes has been observed to occur in the ultraviolet or visible light range.…”