Multifunctional self-assembled peptide nanoparticles for multimodal imaging-guided enhanced theranostic applications against glioblastoma multiforme.
Syed Faheem Askari RizviAzam AliMunir AhmadShuai MuHaixia ZhangPublished in: Nanoscale advances (2021)
The synthesis of self-assembled peptide nanoparticles using a facile one-pot synthesis approach is gaining increasing attention, allowing therapy in combination with diagnosis. Their drawback is limited diagnostic potential, which can be improved after necessary modifications and efficacious functionalization. Herein, a cyclic heptapeptide having the Arg-Gly-Asp-Lys-Leu-Ala-Lys sequence was modified by conjugation of the ε-amino group of the terminal lysine residue with diethylenetriamine pentaacetic acid (DTPA) as a bifunctional chelating agent (BFC) for radiolabeling with a γ-emitting radionuclide ( 99m Tc, half-life 6.01 h; energy 140 keV). Further, the free amino group of the middle lysine residue was successfully conjugated with near-infrared fluorescence (NIRF) dye Cyanine5.5 N -succinimidyl ester (Ex/Em = 670/701 nm) by a co-assembly method to form newly designed novel NIRF dye conjugated self-assembled peptide-DTPA (Cy5.5@SAPD) nanoparticles. The fluorescent nanoparticle formation was confirmed by using a fluorescence spectrophotometer (Ex/Em = 650/701 nm), and the transmission electron microscope (TEM) images showed a size of ∼ 40 nm with a lattice fringe distance of 0.294 nm. Cytotoxicity and confocal laser scanning microscopy (CLSM) studies showed that these nanoparticles possess a high affinity for the α v β 3 -integrin receptor overexpressed on brain tumor glioblastoma with an EC 50 = 20 μM. Moreover, these nanoparticles were observed to have potential to internalize into U87MG cells more prominently than HEK-293 cancer cells and induce apoptosis. The apoptosis assay showed 79.5% apoptotic cells after 24 h treatment of Cy5.5@SAPD nanoparticles. Additionally, these nanoparticles were also radiolabeled with 99m Tc for the single photon emission computed tomography (SPECT) imaging study in tumor-bearing female Balb/c mice. The excellent imaging feature of Cy5.5@SAPD- 99m Tc nanoparticles as a multimodal (SPECT/NIRF) diagnostic probe, as well as noteworthy therapeutic potential was observed. The results suggested that our newly designed novel dual-targeting dual-imaging nanoparticles may serve as an admirable theranostic probe to treat brain tumor glioblastoma multiforme.
Keyphrases
- photodynamic therapy
- high resolution
- cell cycle arrest
- computed tomography
- quantum dots
- induced apoptosis
- cell death
- endoplasmic reticulum stress
- fluorescence imaging
- oxidative stress
- machine learning
- magnetic resonance imaging
- deep learning
- mesenchymal stem cells
- stem cells
- working memory
- high throughput
- amino acid
- pet ct
- highly efficient
- magnetic resonance
- pi k akt
- climate change
- cell proliferation
- cell therapy
- living cells
- light emitting
- label free
- human health