Recent Development of Photofunctional Transition Metal−Peptide Conjugates for Bioimaging and Therapeutic Applications

Abstract

Peptides are attractive for diagnostic and therapeutic applications due to their small molecular size, ease of synthesis and chemical modifications, high target affinity and specificity, efficient tissue penetration, and low immunogenicity. In the past decade, there has been enormous interest in the utilization of photofunctional transition metal complexes as cellular probes, bioimaging reagents, and therapeutic agents. The interest stems from the intriguing photophysical and photochemical properties of the complexes, including large Stokes’ shifts, long emission lifetimes, high photostability, and high singlet oxygen‐photosensitization efficiency. In this Review, we summarize recent advances in the development of photofunctional transition metal−peptide conjugates for bioimaging and therapeutic applications, with a focus on the cellular uptake, intracellular localization, and (photo)cytotoxic activity of the conjugates. Our perspective on the current challenges and future development of photofunctional transition metal−peptide conjugates as diagnostic and therapeutic tools is also provided.

Luminescent iridium(iii)–peptide bioconjugates for bioanalytical and biomedical applications

“…Furthermore, the introduction of cationic and lipophilic iridium(III) complex can overcome another drawback of peptides: their low metabolic stability and poor oral bioavailability. 43,44 In the field of peptide chemistry, certain strategies for improving the stability of peptides have been explored, such as cyclization, increasing the steric bulk of side chains, D-amino acids, N-acetylation and C-amidation (N-methylation, modification in the end of peptide by polyethylene glycol) or adding fatty chains. 45,46 Thus, conjugation with iridium(III) complexes could provide an alternative method to improve peptide stability, complementing existing techniques.…”

“…A variety of iridium(III) complexes functionalized with bioactive peptides have been extensively applied in cell imaging, drug discovery and other areas. [54][55][56] However, although a few reviews describing metal-peptide bioconjugates have been published, 44,51,[57][58][59][60][61] specific reviews on the bioanalytical and biomedical applications of iridium(III)-peptide bioconjugates are scarce. In this review, we summarize the interactions between iridium(III) complexes and peptides and the emerging applications of iridium(III)-peptide bioconjugates in biomedical fields (Scheme 1), highlighting their widespread application for targeted luminescent imaging and as therapeutic agents.…”

Recent Advances in Bioconjugated Transition Metal Complexes for Cancer Therapy

“…In addition to their functional or structural behaviour, metal-based compounds can act as: (i) carriers for active ligands, (ii) catalysts or (iii) photoactivable species [15]. More recently, the classification of metallodrugs has been improved by adding more detailed classes such as: (i) bioconjugated metallodrugs, (ii) inhibitors of enzymes via substrate and metabolite mimics, (iii) redox-active derivatives [16], (iv) photoactivable compounds for photodynamic and photoactivated therapies [17][18][19][20], (v) metal complexes for delivery and release of pharmacologically active ligands, (vi) catalytic drugs [20,21], (vii) radiometals and radioactive agents for radio-imaging and radiotherapy [20,21] and (viii) magnetic resonance imaging (MRI) contrast agents [22].…”

Development of Wireless Power-Transmission-Based Photodynamic Therapy for the Induction of Cell Death in Cancer Cells by Cyclometalated Iridium(III) Complexes

“…It has been proposed that cyclometalated iridium(III) (Ir(III)) complexes would be potent candidates of PSs for PDT [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. We previously reported on the design and synthesis of cyclometalated iridium(III) complexes as luminescence pH sensors and specific probes for intracellular organelles such as mitochondria and lysosomes.…”