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

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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.
Original languageAmerican English
JournalDalton Transactions
Volume47
DOIs
StatePublished - Feb 15 2018

Disciplines

  • Biochemistry, Biophysics, and Structural Biology
  • Biochemistry

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