Iron-silicate-coated porous silicon nanoparticles for in situ ROS self-generation.

Porous silicon nanoparticles (pSiNPs) have gained attention from drug delivery systems (DDS) due to their biocompatibility, high drug-loading efficiency, and facile surface modification. To date, many surface chemistries of pSiNPs have been developed to maximize the merits and overcome the drawbacks of pSiNPs. In this work, we newly disclosed a formulation, iron-silicate-coated pSiNPs (Fe-pSiNPs-NCS), using the surface modification method with iron-silicate and 3-isothiocyanatopropyltriethoxysilane (TEPITC). Fe-pSiNPs-NCS demonstrated effective reactive-oxygen species (ROS) self-generation ability via a Fenton-like reaction of iron-silicate and in situ hydrogen peroxide (H2O2) generation of TEPITC on the surface of pSiNPs, resulting in excellent anticancer effect in U87MG cancer cells. Moreover, we confirmed that Fe-pSiNPs-NCS could be used as a drug delivery carrier as it was proven that anticancer drugs (doxorubicin, SN-38) were loaded into Fe-pSiNPs-NCS with high-loading efficiency. These findings could offer efficient strategies for developing nanotherapeutics in biomedical fields.

Porous silicon surface modification via a microwave-induced in situ cyclic disulfide (S-S) cleavage and Si-S bond formation.

Porous silicon (pSi) materials have gained a great deal of attention from various research fields, and their surface-functionalization is one of the critical points for their applications. In this study, a new surface modification method of Si-H-terminated pSi materials via microwave-induced Si-S bond formation is disclosed. The silicon hydride (Si-H) functionality on the pSi surface could react with the 5-membered cyclic disulfide (S-S) compound (DL-α-lipoic acid in this study) by microwave-induced in situ S-S bond cleavage and Si-S bond formation. This surface chemistry is fast responsive (<10 min) and more efficient than other methods such as vortexing, heating stirring, or ultrasonication. The reaction maintains the primary porous structure of pSi materials including pSi wafer, pSi rugate filer, and pSi nanoparticles. An additional functional group such as carboxylic acid is demonstrated to be readily introducible on the pSi surface for further applications. Overall, this study has successfully demonstrated the porous silicon surface modification via a microwave-induced in situ cyclic disulfide (S-S) cleavage and Si-S bond formation.

SIWV tetrapeptide and ROS-responsive prodrug conjugate for advanced glioblastoma therapy.

A new conjugate formulation, SIWV-PB-SN, based on glioblastoma (GBM)-homing SIWV tetrapeptide and an ROS-responsive prodrug is reported. SIWV-PB-SN selectively penetrates the GBM cells and releases anti-GBM drug (SN-38) via ROS-induced linker cleavage. This study presents a new insight for a more advanced therapeutic approach to overcoming GBM.

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.

Thermally induced silane dehydrocoupling on porous silicon nanoparticles for ultra-long-acting drug release.

Here, we report an ultra-long-acting drug release nano-formulation based on porous silicon nanoparticles (pSiNPs) that are prepared by thermally induced silane dehydrocoupling and lipid-coating. This robust formulation offers the ability to release an anticancer drug, for up to 2 weeks, in various biological environments; pH 7.4 buffer, cancer cells, and tumor xenograft model.

Thermally Induced Silane Dehydrocoupling: Hydrophobic and Oleophilic Filter Paper Preparation for Water Separation and Removal from Organic Solvents.

Organic solvents with high purity are essential in various fields such as optical, electronic, pharmaceutical, and chemical areas to prevent low-quality products or undesired side-products. Constructing methods to remove impurities such as water residue in organic solvents has been a significant challenge. Within this article, we report for the first time a new method for the preparation of hydrophobic and oleophilic filter paper (named OCFP), based on thermally induced silane dehydrocoupling between cellulose-based filter paper and octadecylsilane. We comprehensively characterized OCFP using various characterization techniques (FTIR, XPS, XRD, and EDS). OCFP showed super-hydrophobic and oleophilic properties as well as remarkable water separation and removal efficiency (>93%) in various organic solvents with sustained reusability. In addition, the analytical results both before and after filtration of an NMR solvent using OCFP indicated that OCFP has an excellent solvent drying efficiency. This work presents a new strategy for the development of super-hydrophobic cellulose-based filter paper, which has great potential for solvent drying and water separation.

Self-Activating Therapeutic Nanoparticle: A Targeted Tumor Therapy Using Reactive Oxygen Species Self-Generation and Switch-on Drug Release.

One of the recent advances in nanotechnology within the medical field is the development of a nanoformulation of anticancer drugs or photosensitizers. Cancer cell-specific drug delivery and upregulation of the endogenous level of reactive oxygen species (ROS) are important in precision anticancer treatment. Within our article, we report a new therapeutic nanoformulation of cancer cell targeting using endogenous ROS self-generation without an external initiator and a switch-on drug release (ROS-induced cascade nanoparticle degradation and anticancer drug generation). We found a substantial cellular ROS generation by treating an isothiocyanate-containing chemical and functionalizing it onto the surface of porous silicon nanoparticles (pSiNPs) that are biodegradable and ROS-responsive nanocarriers. Simultaneously, we loaded an ROS-responsive prodrug (JS-11) that could be converted to the original anticancer drug, SN-38, and conducted further surface functionalization with a cancer-targeting peptide, CGKRK. We demonstrated the feasibility as a cancer-targeting and self-activating therapeutic nanoparticle in a pancreatic cancer xenograft mouse model, and it showed a superior therapeutic efficacy through ROS-induced therapy and drug-induced cell death. The work presented is a new concept of a nanotherapeutic and provides a more feasible clinical translational pathway.

AIEgen-based nanoprobe for the ATP sensing and imaging in cancer cells and embryonic stem cells.

A turn-on fluorescent nanoprobe (named AAP-1), based on an aggregation-induced emission luminogen (AIEgen), is disclosed for the detection of adenosine triphosphate (ATP), which is an essential element in the biological system. Organic fluorophore (named TPE-TA) consists of tetraphenylethylene (TPE, sensing and signaling moiety) and mono-triamine (TA, sensing moiety), and it forms an aggregated form in aqueous media as a nanoprobe AAP-1. The nanoprobe AAP-1 has multiple electrostatic interactions as well as hydrophobic interactions with ATP, and it displays superior selectivity toward ATP, reliable sensitivity, with a detection limit around 0.275 ppb, and fast responsive (signal within 10 s). Such a fluorescent probe to monitor ATP has been actively pursued throughout fundamental and translational research areas. In vitro assay and a successful cellular ATP imaging application was demonstrated in cancer cells and embryonic stem cells. We expect that our work warrants further ATP-related studies throughout a variety of fields.

A brain tumor-homing tetra-peptide delivers a nano-therapeutic for more effective treatment of a mouse model of glioblastoma.

Organ-specific cell-penetrating peptides (CPPs) are a class of molecules that can be highly effective at delivering therapeutic cargoes, and they are currently of great interest in cancer treatment strategies. Herein, we describe a new CPP (amino acid sequence serine-isoleucine-tyrosine-valine, or SIWV) that homes to glioblastoma multiforme (GBM) brain tumor tissues with remarkable specificity in vitro and in vivo. The SIWV sequence was identified from an isoform of annexin-A3 (AA3H), a membrane-interacting human protein. The mechanism of intracellular permeation is proposed to follow a caveolin-mediated endocytotic pathway, based on in vitro and in vivo receptor inhibition and genetic knockdown studies. Feasibility as a targeting agent for therapeutics is demonstrated in a GBM xenograft mouse model, where porous silicon nanoparticles (pSiNPs) containing the clinically relevant anticancer drug SN-38 are grafted with SIWV via a poly-(ethylene glycol) (PEG) linker. The formulation shows enhanced in vivo targeting ability relative to a formulation employing a scrambled control peptide, and significant (P < 0.05) therapeutic efficacy relative to free SN-38 in the GBM xenograft animal model.

A bright blue fluorescent dextran for two-photon in vivo imaging of blood vessels.

Fluorescence-based in vivo imaging is one of the most important tools for monitoring of biological processes in cells and tissues of live animal models. Fluorescence imaging agents have also been used to monitor the microcirculation. Tracking microcirculation of the blood is vital to gain further insight into various vascular disease-related anomalies within the human body. As monitoring of vascular circulation is performed with visualization of both immune cells and pathogens, which are mainly labelled with red and green, the favorable color option for blood vessels could be blue. However, currently available blueish color-labeled agents for vascular monitoring is generally confronted with quick bleaching, because of its short excitation and emission wavelengths. Hereby, what we propose in this report is a newly generated bright blue fluorescent dextran, named HCD-70K that monitors the blood vessels using blue and inter-compatible typical fluorescent materials. DBCO-functionalized dextran-70K was fabricated with hydroxy-coumarin dye via metal-free bioorthogonal click chemistry, and generated HCD-70K, which can flow within the blood vessel and decipher the whole structure of the blood vessel successfully. The synthesis, spectroscopic analysis, and quantum chemical calculations were conducted. Using two-photon microscopy, efficient deep in vivo blood vessel imaging of a mouse model revealed exceptional bio-imaging capabilities of the HCD-70K and consequently it provided a promising opportunity for efficient vascular visualization in various research areas.

Systematic Degradation Rate Analysis of Surface-Functionalized Porous Silicon Nanoparticles.

Porous silicon nanoparticles (pSiNPs) have been utilized within a wide spectrum of biological studies, as well as in chemistry, chemical biology, and biomedical fields. Recently, pSiNPs have been constantly coming under the spotlight, mostly in biomedical applications, due to their advantages, such as controlled-release drug delivery in vivo by hydrolysis-induced degradation, self-reporting property through long life-time photoluminescence, high loading efficiency of substrate into pore, and the homing to specific cells/organ/bacteria by surface functionalization. However, the systematic degradation rate analysis of surface-functionalized pSiNPs in different biological media has not been conducted yet. In this paper, we prepared four different surface-functionalized pSiNPs samples and analyzed the degradation rate in six different media (DI H2O (deionized water), PBS (phosphate-buffered saline), HS (human serum), DMEM (Dulbecco's modified Eagle's medium), LB (lysogeny broth), and BHI (brain heart infusion)). The obtained results will now contribute to understanding the correlation between surface functionalization in the pSiNPs and the degradation rate in different biological media. The characterized data with the author's suggestions will provide useful insights in designing the new pSiNPs formulation for biomedical applications.

Fabrication of blue-fluorescent nanodiamonds modified with alkyl isocyanate for cellular bioimaging.

This paper describes the fabrication of water-dispersible nanodiamond (ND) clusters with blue fluorescence for cellular bioimaging. Poly(ethylene glycol) carboxyl methyl acid (mPEG-COOH) and alkyl isocyanates with different chain lengths were conjugated onto the surface of the ND clusters for water dispersibility and fluorescence via carbodiimide chemistry. The relative fluorescence intensity was increased with the increases in the chain length of alkyl isocyanate and also their conjugated concentration. The ND clusters (average size of 37.6 nm and zeta potential of 26.6 mV) with mPEG-COOH and octadecyl isocyanate (ODI) emitted relatively higher blue fluorescence intensity under excitation at 350 nm as well as favorable water dispersibility. After cellular uptake of the ND clusters, blue fluorescence inside the cells was confirmed by confocal laser scanning microscopy. The ND clusters conjugated with mPEG-COOH and ODI can potentially be used for cellular bioimaging.

Photodynamic and photothermal tumor therapy using phase-change material nanoparticles containing chlorin e6 and nanodiamonds.

This paper describes the fabrication and evaluation of phase-change material (PCM) nanoparticles containing chlorin e6 (Ce6) and nanodiamonds (NDs) for photodynamic and photothermal approaches for tumor therapy, respectively. The temperature of the PCM nanoparticles containing NDs (ND/PCM, 0.5mg/mL in water) is increased to 45°C during laser exposure for 5min. The singlet oxygen generation intensity of PCM nanoparticles containing Ce6 and NDs (Ce6/ND/PCM) is gradually increased with respect to the laser exposure time. Also, the release of Ce6 from Ce6/ND/PCM can be controlled in an on-and-off manner using laser. Cell ablation tests reveal that Ce6/ND/PCM greatly ablates KB cells upon laser exposure, which is attributed to both the temperature increase in the media and singlet oxygen generation by the released Ce6. In an animal model, tumor volume is notably reduced over time after the intratumoral injection of Ce6/ND/PCM and subsequent laser exposure with a higher efficiency compared to ND/PCM. The Ce6/ND/PCM can be a promising nanomedicine for tumor therapy.