Evaluation of novel platinum(ii) based AIE compound-encapsulated mesoporous silica nanoparticles for cancer theranostic application

Abstract

Advanced biomedical research has established that cancer is a multifactorial disorder which is highly heterogeneous in nature and responds differently to different treatment modalities, due to which constant monitoring of therapy response is becoming extremely important. To accomplish this, different theranostic formulations have been evaluated. However, most of them are found to suffer from several limitations extending from poor resolution, radiation damage, to high costs. In order to develop a better theranostic modality, we have designed and synthesized a novel platinum(ii)-based 'aggregation induced emission' (AIE) molecule (named BMPP-Pt) which showed strong intra-cellular fluorescence and also simultaneously exhibited potent cytotoxic activity. Due to this dual functionality, we wanted to explore the possibility of using this compound as a single molecule based theranostic modality. This compound was characterized using elemental analysis, NMR and IR spectroscopy, mass spectrometry and single crystal X-ray structure determination. BMPP-Pt was found to exhibit a high AIE property with emission maxima at 497 nm. For more efficient cancer cell targeting, BMPP-Pt was encapsulated into mesoporous silica nanoparticles (Pt-MSNPs) and the MSNPs were further surface modified with an anti-EpCAM aptamer (Pt-MSNP-E). Pt-MSNPs exhibited higher intracellular fluorescence compared to free BMPP-Pt, though both of them induced a similar degree of cell death via the apoptosis pathway, possibly via cell cycle arrest in the G1 phase. Anti-EpCAM aptamer modification was found to increase both cytotoxicity and intracellular fluorescence compared to unmodified MSNPs. Our study showed that EpCAM functionalized BMPP-Pt loaded MSNPs can efficiently internalize and induce apoptosis of cancer cells as well as show strong intracellular fluorescence. This study provides clues towards the development of a potential single compound based theranostic modality in future.

Cyclometalated Pt Complexes of CNC Pincer Ligands: Luminescence and Cytotoxic Evaluation

“…The analysis was facilitated through the observation of the 195 Pt satellites on 1 [Pt(CNC)(L)] complexes, 5,12−16,18,19,24,34,40−43 while for a few derivatives, short Pt•••Pt contacts of 3−4 Å have been reported. 15,38 Short Pt•••Pt contacts in such systems have also been intentionally constructed to induce aggregation-induced emission (AIE). 5,8,9,11,18,44,45 This has been observed in related cyclometalated Pt(II) complexes 3−6,37−39,43−46 and might also occur for the complexes presented here.…”

Preparation and Study of the Antibacterial Applications and Oxidative Stress Induction of Copper Maleamate-Functionalized Mesoporous Silica Nanoparticles

“…However, mesoporous silica-based materials have also been functionalized with metallodrugs of interest in cancer treatment, such as platinum compounds [7,8,9,10,11,12,13,14], titanium compounds [10,15,16,17,18,19,20,21,22,23], tin compounds [22,24,25] and even ruthenium photosensitizers [26], observing promising anticancer activity and a potential future application in clinical trials. The cellular action of these metallodrug-functionalized nanostructured silica-based materials showed that, in most cases, the nanosystems do not release the metallodrug to the biological medium (or the metallodrug release rates are very low), and they usually act as “non-classical” drug-delivery systems, whose cytotoxic activity is due to the action of the entire nanoparticle.…”

Aptamer-Enabled Nanomaterials for Therapeutics, Drug Targeting and Imaging

“…The signal materials coupled to the functional vehicle are diverse, including but not limited to NIR dyes, radionuclide chelation agents (eg. DOTA) [ 184 ], two-photon dyes [ 181 ], MRI contrast agents, or aggregation induced emission (AIE) compounds [ 185 ]. They are usually conjugated to aptamers or the surface of silicas or are encapsulated into the shell of MSNs.…”

“…This concept might facilitate the instant detection or intervention in cancer therapy. Besides that, Pasha et al in 2018 designed an anti-EpCAM aptamer-functionalized MSNs system to encapsulate a dual functional compound, platinum-based “aggregation induced emission (AIE)” molecule (BMPP-Pt) [ 185 ] ( Figure 10 b). The component of BMPP-Pt is bis(diphenylphosphino)methane phenylpyridine platinum (II) chloride, holds potentials for theranostic applications in cancers by inducing cell apoptosis and emitting dose-dependent fluorescent signals.…”