Jin-sil Choi

Heterostructured magnetic nanoparticles: their versatility and high performance capabilities

Magnetic nanoparticles exhibit unique nanoscale properties and their utilization for various magnetic systems is of significant interest. Especially, heterostructured magnetic nanoparticles are emerging as next-generation materials due to their synergistically enhanced magnetism and potential multifunctionalities. Herein, we overview the recent advances in the development of magnetic nanoparticles with a focus on multicomponent heterostructured nanoparticles including alloys, core-shells, and binary superlattices synthesized via nonhydrolytic methods. Their multifunctionalites and high performance capabilities are demonstrated for applications in high density magnetic storages, chemical catalysis, and biomedical separation and diagnostics.

Programming thermoresponsiveness of NanoVelcro substrates enables effective purification of circulating tumor cells in lung cancer patients.

Unlike tumor biopsies that can be constrained by problems such as sampling bias, circulating tumor cells (CTCs) are regarded as the “liquid biopsy” of the tumor, providing convenient access to all disease sites, including primary tumor and fatal metastases. Although enumerating CTCs is of prognostic significance in solid tumors, it is conceivable that performing molecular and functional analyses on CTCs will reveal much significant insight into tumor biology to guide proper therapeutic intervention. We developed the Thermoresponsive NanoVelcro CTC purification system that can be digitally programmed to achieve an optimal performance for purifying CTCs from non-small cell lung cancer (NSCLC) patients. The performance of this unique CTC purification system was optimized by systematically modulating surface chemistry, flow rates, and heating/cooling cycles. By applying a physiologically endurable stimulation (i.e., temperature between 4 and 37 °C), the mild operational parameters allow minimum disruption to CTCs’ viability and molecular integrity. Subsequently, we were able to successfully demonstrate culture expansion and mutational analysis of the CTCs purified by this CTC purification system. Most excitingly, we adopted the combined use of the Thermoresponsive NanoVelcro system with downstream mutational analysis to monitor the disease evolution of an index NSCLC patient, highlighting its translational value in managing NSCLC.

Double-Effector Nanoparticles: A Synergistic Approach to Apoptotic Hyperthermia

Highly efficient apoptotic hyperthermia is achieved using a double-effector nanoparticle that can generate reactive oxygen species (ROS) and heat. ROS render cancer cells more susceptible to subsequent heat treatment, which remarkably increases the degree of apoptotic cell death. Xenograft tumors (100 mm(3)) in mice are completely eliminated within 8 days after a single mild magnetic hyperthermia treatment at 43 °C for 30 min.

Design Considerations of Iron-Based Nanoclusters for Noninvasive Tracking of Mesenchymal Stem Cell Homing

Stem-cell-based therapies have attracted considerable interest in regenerative medicine and oncological research. However, a major limitation of systemic delivery of stem cells is the low homing efficiency to the target site. Here, we report a serendipitous finding that various iron-based magnetic nanoparticles (MNPs) actively augment chemokine receptor CXCR4 expression of bone-marrow-derived mesenchymal stem cells (MSCs). On the basis of this observation, we designed an iron-based nanocluster that can effectively label MSCs, improve cell homing efficiency, and track the fate of the cells in vivo. Using this nanocluster, the labeled MSCs were accurately monitored by magnetic resonance imaging and improved the homing to both traumatic brain injury and glioblastoma models as compared to unlabeled MSCs. Our findings provide a simple and safe method for imaging and targeted delivery of stem cells and extend the potential applications of iron-based MNPs in regenerative medicine and oncology.

Pretargeted Positron Emission Tomography Imaging That Employs Supramolecular Nanoparticles with in Vivo Bioorthogonal Chemistry

A pretargeted oncologic positron emission tomography (PET) imaging that leverages the power of supramolecular nanoparticles with in vivo bioorthogonal chemistry was demonstrated for the clinically relevant problem of tumor imaging. The advantages of this approach are that (i) the pharmacokinetics (PKs) of tumor-targeting and imaging agents can be independently altered via chemical alteration to achieve the desired in vivo performance and (ii) the interplay between the two PKs and other controllable variables confers a second layer of control toward improved PET imaging. In brief, we utilized supramolecular chemistry to synthesize tumor-targeting nanoparticles containing transcyclooctene (TCO, a bioorthogonal reactive motif), called TCO⊂SNPs. After the intravenous injection and subsequent concentration of the TCO⊂SNPs in the tumors of living mice, a small molecule containing both the complementary bioorthogonal motif (tetrazine, Tz) and a positron-emitting radioisotope ((64)Cu) was injected to react selectively and irreversibly to TCO. High-contrast PET imaging of the tumor mass was accomplished after the rapid clearance of the unreacted (64)Cu-Tz probe. Our nanoparticle approach encompasses a wider gamut of tumor types due to the use of EPR effects, which is a universal phenomenon for most solid tumors.

Molecular recognition enables nanosubstrate-mediated delivery of gene-encapsulated nanoparticles with high efficiency.

Substrate-mediated gene delivery is a promising method due to its unique ability to preconcentrate exogenous genes onto designated substrates. However, many challenges remain to enable continuous and multiround delivery of the gene using the same substrates without depositing payloads and immobilizing cells in each round of delivery. Herein we introduce a gene delivery system, nanosubstrate-mediated delivery (NSMD) platform, based on two functional components with nanoscale features, including (1) DNA⊂SNPs, supramolecular nanoparticle (SNP) vectors for gene encapsulation, and (2) Ad-SiNWS, adamantane (Ad)-grafted silicon nanowire substrates. The multivalent molecular recognition between the Ad motifs on Ad-SiNWS and the β-cyclodextrin (CD) motifs on DNA⊂SNPs leads to dynamic assembly and local enrichment of DNA⊂SNPs from the surrounding medium onto Ad-SiNWS. Subsequently, once cells settled on the substrate, DNA⊂SNPs enriched on Ad-SiNWS were introduced through the cell membranes by intimate contact with individual nanowires on Ad-SiNWS, resulting in a highly efficient delivery of exogenous genes. Most importantly, sequential delivery of multiple batches of exogenous genes on the same batch cells settled on Ad-SiNWS was realized by sequential additions of the corresponding DNA⊂SNPs with equivalent efficiency. Moreover, using the NSMD platform in vivo, cells recruited on subcutaneously transplanted Ad-SiNWS were also efficiently transfected with exogenous genes loaded into SNPs, validating the in vivo feasibility of this system. We believe that this nanosubstrate-mediated delivery platform will provide a superior system for in vitro and in vivo gene delivery and can be further used for the encapsulation and delivery of other biomolecules.

A High-Throughput Platform for Formulating and Screening Multifunctional Nanoparticles Capable of Simultaneous Delivery of Genes and Transcription Factors

Simultaneous delivery of multiple genes and proteins (e.g., transcription factors; TFs) is an emerging issue surrounding therapeutic research due to their ability to regulate cellular circuitry. Current gene and protein delivery strategies, however, are based on slow batch synthesis, which is ineffective, poorly controlled, and incapable of simultaneous delivery of both genes and proteins with synergistic functions. Consequently, advances in this field have been limited to in vitro studies. Here, by integrating microfluidic technologies with a supramolecular synthetic strategy, we present a high-throughput approach for formulating and screening multifunctional supramolecular nanoparticles (MFSNPs) self-assembled from a collection of functional modules to achieve simultaneous delivery of one gene and TF with unprecedented efficiency both in vitro and in vivo. We envision that this new approach could open a new avenue for immunotherapy, stem cell reprogramming, and other therapeutic applications.

Characterization and luminescence properties of Alq3 films grown by ionized-cluster-beam deposition, neutral-cluster-beam deposition and thermal evaporation

Tris-(8-hydroxyquinoline) aluminum (Alq3) films have been grown on silicon substrates by several techniques: neutral-cluster-beam deposition; thermal evaporation; and ionized-cluster-beam deposition technique. The films were characterized by low angle X-ray reflectivity, atomic force microscopy, Fourier transformed infrared (FTIR) spectroscopy and photoluminescence. According to the FTIR spectroscopy measurement, the spectra of all the Alq3 samples show almost the same signals of atomic binding regardless of the process conditions. However, the photoluminescence intensities of the films are different. When all the films are adjusted to the same thickness, neutral-cluster-beam deposition films show more intense photoluminescence than the thermal-evaporated ones, while ionized-cluster-beam deposition samples are found to be inferior in intensity. Since the photoluminescence intensity of the 8-hydroxyquinoline aluminum layers is one of the important factors for the performance of organic light emitting devices, the neutral-cluster-beam deposition seems to be a promising method for the film deposition of organic electroluminescence materials.

Supramolecular Nanosubstrate-Mediated Delivery for Reprogramming and Transdifferentiation of Mammalian Cells

Supramolecular nanosubstrate-mediated delivery (SNSMD) leverages the power of molecular self-assembly and a nanostructured substrate platform for the low toxicity, highly efficient co-delivery of biological factors encapsulated in a nanovector. Human fibroblasts are successfully reprogrammed into induced pluripotent stems and transdifferentiated into induced neuronal-like cells.

A magnetic resonance tuning sensor for the MRI detection of biological targets

Sensors that detect specific molecules of interest in a living organism can be useful tools for studying biological functions and diseases. Here, we provide a protocol for the construction of nanosensors that can noninvasively detect biologically important targets with magnetic resonance imaging (MRI). The key operating principle of these sensors is magnetic resonance tuning (MRET), a distance-dependent phenomenon occurring between a superparamagnetic quencher and a paramagnetic enhancer. The change in distance between the two magnetic components modulates the longitudinal (T1) relaxivity of the enhancer. In this MRET sensor, distance variation is achieved by interactive linkers that undergo binding, cleavage, or folding/unfolding upon their interaction with target molecules. By the modular incorporation of suitable linkers, the MRET sensor can be applied to a wide range of targets. We showcase three examples of MRET sensors for enzymes, nucleic acid sequences, and pH. This protocol comprises three stages: (i) chemical synthesis and surface modification of the quencher, (ii) conjugation with interactive linkers and enhancers, and (iii) MRI sensing of biological targets. The entire procedure takes up to 3 d.This protocol describes the synthesis of magnetic resonance tuning (MRET) sensors. The sensors consist of two magnetic components separated by a linker and can be modularly designed for targets such as enzymes, nucleic acid sequences, and pH values.