A Deep Dive: SIWV Tetra-Peptide Enhancing the Penetration of Nanotherapeutics into the Glioblastoma.

Glioblastoma multiforme (GBM) is the most aggressive malignant tumor. It is difficult to regulate GBM using conventional chemotherapy-based methods due to its anatomical structure specificity, low drug targeting ability, and limited penetration depth capability to reach the tumor interior. Numerous approaches have been proposed to overcome such issues, including nanoparticle-based drug delivery system (DDS) with the development of GBM site targeting and penetration depth enhancing moieties (e.g., peptides, sugars, proteins, etc.). In this study, we prepared four different types of nanoparticles, which are based on porous silicon nanoparticles (pSiNPs) incorporating polyethylene glycol (PEG), iRGD peptide (well-known cancer targeting peptide), and SIWV tetra-peptide (a recently disclosed GBM-targeting peptide), and analyzed their deep-tumor penetration abilities in cell spheroids, in GBM patient-derived tumoroids, and in GBM xenograft mice. We found that SIWV tetra-peptide significantly enhanced the penetration depth of pSiNPs, and its therapeutic formulation (temozolomide-loaded/SIWV-functionalized pSiNPs) showed a higher anticancer efficacy compared with other formulations. These findings hold great promise for the development of nanotherapeutics and peptide-conjugated drugs for GBM.

Neuroprotective effect of single-wall carbon nanotubes with built-in peroxidase-like activity against ß-amyloid-induced neurotoxicity.

Carbon nanotubes (CNTs) have emerged as a leading nanomaterial for biomedical applications because of their extraordinary properties, which make them useful as delivery vehicles for drugs, proteins, and DNA into cells. However, the numerous applications of carbon nanotubes inevitably increase the potential risk of this nanomaterial. To address this issue, it is necessary to develop protocols for the effective and safe degradation of CNTs. In this study, we demonstrate a self-degradation route for single-wall carbon nanotubes mediated by the built-in peroxidase-like activity of bacterial magnetic nanoparticles (BMPs). Biocompatible BMPs which originated from Magnetospirillum sp. AMB-1 were directly conjugated through covalent bonding to functionalized SWNTs (f-SWNTs) without any additional functionalization processes. This SWNT-BMP hybrid was proven to exhibit highly synergetic peroxidase-like activity, and BMPs act as a highly effective intrinsic peroxidase for the self-degradation of BMP-decorated SWNTs. Moreover, it was shown to be an inhibitor that reduces the formation of ß-amyloid (Aß) fibrils, which are considered a key element in Alzheimer's disease. Thereby the SWNT-BMP hybrid exerts neuroprotective effects against ß-amyloid (Aß) fibrillation-induced neurotoxicity in SH-SY5Y human neuroblastoma cells. These results suggest that the SWNT-BMP hybrid could offer a new approach for treating or preventing neurodegenerative diseases.

Magnetic manipulation of bacterial magnetic nanoparticle-loaded neurospheres.

Specific targeting of cells to sites of tissue damage and delivery of high numbers of transplanted cells to lesion tissue in vivo are critical parameters for the success of cell-based therapies. Here, we report a promising in vitro model system for studying the homing of transplanted cells, which may eventually be applicable for targeted regeneration of damaged neurons in spinal cord injury. In this model system, neurospheres derived from human neuroblastoma SH-SY5Y cells labeled with bacterial magnetic nanoparticles were guided by a magnetic field and successfully accumulated near the focus site of the magnetic field. Our results demonstrate the effectiveness of using an in vitro model for testing bacterial magnetic nanoparticles to develop successful stem cell targeting strategies during fluid flow, which may ultimately be translated into in vivo targeted delivery of cells through circulation in various tissue-repair models.

Magnetic response of mitochondria-targeted cancer cells with bacterial magnetic nanoparticles.

We first demonstrate the effects of magnetic trapping of mitochondria using aptamer conjugated to bacterial magnetic nanoparticles that allowed targeting of the mitochondrial cytochrome c in the treatment of cancer cells. Our findings offer a new approach for targeted cell therapy, with the advantage of remote control over subcellular elements.

Cell response induced by internalized bacterial magnetic nanoparticles under an external static magnetic field.

Magnetic nanoparticles are widely used in bioapplications such as imaging and targeting tool. Their magnetic nature allows for the more efficient bioapplications by an external field gradient. However their combined effects have not yet been extensively characterized. Herein, we first demonstrate the biological effects of the communications between internalized bacterial magnetic nanoparticles (BMPs) and an external static magnetic field (SMF) on a standard human cell line. Combination of the BMPs and SMF act as the key factor leading to the alteration of cell structure and the enhanced cell growth. Also, their interaction reduced the apoptotic efficiency of human tumor cells induced by anticancer drugs. Microarray analysis suggests that these phenomena were caused by the alterations of GPCRs-mediated signal transduction originated in the interaction of internalized BMPs and the external SMF. Our findings may offer new approach for targeted cell therapy with the advantage of controlling cell viability by magnetic stimulation.

Biomolecular detection with a thin membrane transducer.

We present a thin membrane transducer (TMT) that can detect nucleic acid based biomolecular reactions including DNA hybridization and protein recognition by aptamers. Specific molecular interactions on an extremely thin and flexible membrane surface cause the deflection of the membrane due to surface stress change which can be measured by a compact capacitive circuit. A gold-coated thin PDMS membrane assembled with metal patterned glass substrate is used to realize the capacitive detection. It is demonstrated that perfect match and mismatch hybridizations can be sharply discriminated with a 16-mer DNA oligonucleotide immobilized on the gold-coated surface. While the mismatched sample caused little capacitance change, the perfectly matched sample caused a well-defined capacitance decrease vs. time due to an upward deformation of the membrane by a compressive surface stress. Additionally, the TMT demonstrated the single nucleotide polymorphism (SNP) capabilities which enabled a detection of mismatching base pairs in the middle of the sequence. It is intriguing that the increase of capacitance, therefore a downward deflection due to tensile stress, was observed with the internal double mismatch hybridization. We further present the detection of thrombin protein through ligand-receptor type recognition with 15-mer thrombin aptamer as a receptor. Key aspects of this detection such as the effect of concentration variation are investigated. This capacitive thin membrane transducer presents a completely new approach for detecting biomolecular reactions with high sensitivity and specificity without molecular labelling and optical measurement.