Hybridization of tumor homing and mitochondria-targeting peptide domains to design novel dual-imaging self-assembled peptide nanoparticles for theranostic applications

Abstract

A unique dual-targeting dual-imaging peptide-based nanoprobe was successfully designed by investigating the cyclic heptapeptide having Arg-Gly-Asp-Lys-Leu-Ala-Lys sequence composed of RGD homing motif and KALK mitochondria targeting motif linked via amide bond. The designed peptide was further modi ed through covalent linkage, characterized and self-assembled to form spherical nanoparticles. The novel Cy5.5-SAPD-99m Tc nanoparticles were tested in vitro for cytotoxicity, cellular uptake, biocompatibility and apoptosis inducing functionalities. The cellular internalization, enhanced cytotoxicity and selective receptor binding capabilities against U87MG cells, excellent dual-imaging potential, improved apoptosis inducing feature by damaging mitochondria and in vivo preclinical investigations suggested that our newly designed novel dual-targeting dual-imaging nanoparticles may serve as an admirable theranostic probe to treat brain tumor glioblastoma multiforme.

Delivering Therapeutics to Glioblastoma: Overcoming Biological Constraints

“…Controlled release systems Gliadel [11,[31][32][33] Biodegradable wafers for the combined delivery of temozolomide and carmustine [34] Biodegradable polymer implants releasing rapamycin [35] Carboxymethylcellulose biopolymer system delivering rhodamine B [36] Hydrogel based co-delivery of paclitaxel and temozolomide [37] Convection enhanced delivery Temozolomide [40] Carboplatin [41] Iron oxide nanoparticles conjugated to epidermal growth factor receptor deletion mutant III antibody (EG-FRVIIIAb)/MRI-guided [43] Nanomaterial Systems Poly(ε-caprolactone) (PCL) based nanoparticle system to deliver the natural growth modulating tripeptide GHK (glycyl-L-histidyl-L-lysine) [58] Nanobubble-based theranostic system consisting of intravenously administered iron-platinum nanoparticles loaded with doxorubicin and surface-functionalized with transferrin [60] Peptide based therapeutics Tumor targeting peptides delivering deliver the oncolytic virus VSV∆M51, in combination with gadolinium [68] Self-assembled spherical nanoparticles containing a peptide probe (Cy5.5-SAPD-99mTc) with mitochondria targeting [69] Peptide derivatives of rabies virus glycoproteins, RVG29 and RVG15-liposome, delivering anticancer chemotherapeutic docetaxel nanoparticles and paclitaxel-cholesterol [70,71] WSW (also called PhrCACET1) peptide fused to paclitaxel nanosuspensions [72] Use of polydopamine (PDA)-coated zein-curcumin nanoparticles functionalized with the peptide G23 [73] Dual peptide nanocomplex created by combining SynB3 (a cell penetration peptide) with PVGLIG (an MMP-2 sensitive peptide) and paclitaxel [77] Focused ultrasound Temozolomide [84] BCNU [85] Liposomal O6-(4-bromothenyl)guanine (O6BTG) [86] Liposome-encapsulated doxorubicin [88] Cisplatin conjugated gold nanoparticles [89] Trastzumab [90] Author…”

“…Self-assembled spherical nanoparticles containing a peptide probe (Cy5.5-SAPD-99mTc) that combines tumor homing ability with mitochondria targeting was found to have promising theranostic possibilities owing to the enhanced apoptosis in GBM cells coupled with imaging functionality [69]. Incorporating both tumor-homing and mitochondriatargeting components helps to increase the specificity of drug delivery.…”

Small Peptide–Based Nanodelivery Systems for Cancer Therapy and Diagnosis

“…RGD peptides conjugated to the nanospheres were intended to specifically target overexpressed αvβ3-integrin receptors on glioblastoma cells. The as-formed 0D nanospheres depicted enhanced apoptosis and anticancer efficacy in both cellular and animal glioblastoma models (Rizvi et al, 2022).…”

“…This peptide was selfassembled to form a spherical nanostructure. These nanostructures showed dual imaging and improved apoptosis by destroying mitochondria (Rizvi et al, 2022).…”

Molecularly Stimuli-Responsive Self-Assembled Peptide Nanoparticles for Targeted Imaging and Therapy

“…SiO 2 @ MCSGs exhibited superoxide dismutase (SOD) and peroxidase (POD) activities. After loading the substrate Zhang et al 176 designed a double-targeted double-imaging agent probe (Cy5.5-SAPD-99 mTc) for glioblastoma multiforme treatment. The cyclic heptapeptide comprised an RGD homing motif and a mitochondria-targeting motif, which targeted caspase3-integrin and KLAK pro-apoptotic motifs, respectively, to induce cancer cell apoptosis by producing ROS and activating caspase-3.…”