Tetraphenylethene-based highly emissive metallacage as a component of theranostic supramolecular nanoparticles

Abstract

A theranostic agent combines diagnostic reporter with therapeutic activity in a single entity, an approach that seeks to increase the efficacy of cancer treatment. Herein, we describe the synthesis of a highly emissive tetraphenylethene-based metallacage using multicomponent coordination-driven self-assembly that exhibits a coordination-triggered aggregation-induced emission (AIE) enhancement. The formation of metallacage-loaded nanoparticles (MNPs) occurs when the assembly is treated with two variants of a 1,2-distearoyl-phosphatidylethanolamine (DSPE)/polyethylene glycol (PEG) conjugate, mPEG-DSPE, and biotin-PEG-DSPE. This combination endows the resultant MNPs with excellent stability and targeting ability, specifically enabling selective delivery of the metallacages to cancer cells that overexpress biotin receptors via receptor-mediated endocytosis. Although the mechanism of activity is based on existing Pt(II) anticancer drugs such as oxaliplatin, carboplatin, and cisplatin, in vitro and in vivo studies indicate that the MNPs are more active and show low systemic activity while also possessing emissive properties that allow for fluorescence-based imaging. This pioneering example of a metallacage that combines biologically active components with AIE imaging establishes supramolecular coordination complexes imbedded within nanoparticles as a promising potential theranostic platform for cancer treatment.ver the past decades, platinum-based coordination complexes have been a mainstay of clinical drugs for the treatment of many solid tumors, including testicular, colorectal, genitourinary, and nonsmall cell lung cancers (1, 2). Cisplatin, oxaliplatin, and carboplatin have been approved as first-line chemotherapeutics for the treatment of carcinoma in combination with other anticancer drugs. However, their chemotherapeutic applications are greatly limited by severe side effects that include acute nephrotoxicity, neurotoxicity, ototoxicity, and emetogenesis (3, 4). The search for low-dose platinum-based drugs/prodrugs with high selectivity to tumor tissues motivates the development of targeting drug delivery systems that may reduce side effects and show an improved therapeutic index. Further modifications are sought to address drawbacks of poor solubility, rapid clearance, and a lack of selectivity (5, 6). Although fluorescence-based techniques provide a means to track the processes of translocation, drug release and excretion of anticancer agents, the aforementioned species are intrinsically nonfluorescent under treatment conditions (7-10).In sharp contrast to the aggregation-caused quenching (ACQ) effect, Tang and colleagues developed a novel class of organic luminogens that are nonemissive in solution but become intensely emissive on aggregation, with pioneering studies based on tetraphenylethene (TPE) and hexaphenylsilole (HPS). This so-called aggregation-induced emission (AIE) effect is attributed to the restriction of intramolecular rotation (RIR) of the aromatic rings of AIEgens (11). Since the discovery of...

Facile Synthesis of Luminescent Ir–Pt–Ir Trimetallic Complexes

“…[1][2][3][4]23] More recently,t he supramolecular photochemistry of d 8 Pt II has emerged,f acilitated by the ability to use coordination-driven self-assembly approachest op repare two-dimensional metallacycles or three-dimensional cages of many different shapes and sizes. In this way,m any luminescent Pt II supramolecular coordination complexes have been prepared, [24][25][26][27][28][29] some of which exhibita ggregation-induced emission [24] or are suitable for cellular imaging applications. [29] In contrast, the supramolecular chemistry of cyclometalated Ir III complexesi sc onsiderablyl ess developed.…”

Host−guest complexation-mediated codelivery of anticancer drug and photosensitizer for cancer photochemotherapy

“…Well-defined signals were observed for the protons of M in the 1 H NMR spectrum (SI Appendix, Fig. S3), suggesting that the resultant speices possessed a discrete and highly symmetric structure (25)(26)(27)(28). Compared with free HPPB, the 1 H NMR signals releted to the pyridyl protons (H 1 and H 2 ) shifted downfield upon formation of M due to the Pt(II)←pyridine coordination interactions (SI Appendix, Fig.…”

Tetraphenylethylene-Based Emissive Supramolecular Metallacages Assembled by Terpyridine Ligands

“…Accordingly, high fluorescent efficiency was mainly observed in their aggregate state, in which the rotations of the benzene rings were restricted effectively. 55 Nonetheless, in the solution state, as well as the isolated supramolecular cage scenario, these nonaggregate supramolecules were still nonemissive or weakly luminescent, 47,48,50,54,[56][57][58][59][60] which severely limited the application prospect of the TPE molecule.…”