The Evolution of Microfluidic-Based Drug-Loading Techniques for Cells and Their Derivatives.

Conventional drug delivery techniques face challenges related to targeting and adverse reactions. Recent years have witnessed significant advancements in nanoparticle-based drug carriers. Nevertheless, concerns persist regarding their safety and insufficient metabolism. Employing cells and their derivatives, such as cell membranes and extracellular vesicles (EVs), as drug carriers effectively addresses the challenges associated with nanoparticle carriers. However, an essential hurdle remains in efficiently loading drugs into these carriers. With the advancement of microfluidic technology and its advantages in precise manipulation at the micro- and nanoscales, as well as minimal sample loss, it has found extensive application in the loading of drugs using cells and their derivatives, thereby fostering the development of drug-loading techniques. This paper outlines the characteristics and benefits of utilizing cells and their derivatives as drug carriers and provides an overview of current drug-loading techniques, particularly those rooted in microfluidic technology. The significant potential for microfluidic technology in targeted disease therapy through drug delivery systems employing cells and their derivatives, is foreseen.

A stepwise multi-stage continuous dielectrophoresis separation microfluidic chip with microfilter structures.

The separation of target microparticles using microfluidic systems owns extensive applications in biomedical, chemical, and materials science fields. Integration of microfluidic sorting systems employing dielectrophoresis (DEP) technology has been widely investigated. However, enhancing separation efficiency, purity, stability, and integration remains a pressing issue. This study proposes a stepwise multi-stage continuous DEP separation microfluidic chip with a microfilter structure. By leveraging a stepwise electrode configuration, a gradient electric field is generated to drive target microparticles along the electric field gradient, thereby enhancing separation efficiency. Innovative integration of a microfilter structure facilitates simultaneous filtration and improves flow field distribution, thus enhancing system stability. Through the synergistic effect of stepwise electrodes and the microfilter structure, superior coupling of electric and flow fields is achieved, consequently improving the sorting purity, separation efficiency, and system stability of the DEP-based microfluidic sorting system. Validation through simulation and separation of polystyrene microspheres demonstrates the excellent particle separation performance of the proposed system. It evidently shows potential for seamless extension to various biological microparticle sorting applications, harboring significant prospects in the biomedical domain field.

An ingestible near-infrared fluorescence capsule endoscopy for specific gastrointestinal diagnoses.

Early diagnosis of gastrointestinal (GI) diseases is important to effectively prevent carcinogenesis. Capsule endoscopy (CE) can address the pain caused by wired endoscopy in GI diagnosis. However, existing CE approaches have difficulty effectively diagnosing lesions that do not exhibit obvious morphological changes. In addition, the current CE cannot achieve wireless energy supply and attitude control at the same time. Here, we successfully developed a novel near-infrared fluorescence capsule endoscopy (NIFCE) that can stimulate and capture near-infrared (NIR) fluorescence images to specifically identify subtle mucosal microlesions and submucosal lesions while capturing conventional white light (WL) images to detect lesions with significant morphological changes. Furthermore, we constructed the first synergetic system that simultaneously enables multi-attitude control in NIFCE and supplies long-term power, thus addressing the issue of excessive power consumption caused by the NIFCE emitting near-infrared light (NIRL). We performed in vivo experiments to verify that the NIFCE can specifically "light up" tumors while sparing normal tissues by synergizing with probes actively aggregated in tumors, thus realizing specific detection and penetration. The prototype NIFCE system represents a significant step forward in the field of CE and shows great potential in efficiently achieving early targeted diagnosis of various GI diseases.

Time and Space Dual-Blockade Strategy for Highly Invasive Nature of Triple-Negative Breast Cancer in Enhanced Sonodynamic Therapy Based on Fe-MOF Nanoplatforms.

Triple-negative breast cancer (TNBC), due to its high malignant degree and strong invasion ability, leads to poor prognosis and easy recurrence, so effectively curbing the invasion of TNBC is the key to obtaining the ideal therapeutic effect. Herein, a therapeutic strategy is developed that curbs high invasions of TNBC by inhibiting cell physiological activity and disrupting tumor cell structural function to achieve the time and space dual-blockade. The time blockade is caused by the breakthrough of the tumor-reducing blockade based on the ferroptosis process and the oxidation-toxic free radicals generated by enhanced sonodynamic therapy (SDT). Meanwhile, alkyl radicals from 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) and 1O2 attacked the organelles of tumor cells under ultrasound (US), reducing the physiological activity of the cells. The attack of free radicals on the cytoskeleton, especially on the proteins of F-actin and its assembly pathway, achieves precise space blockade of TNBC. The damage to the cytoskeleton and the suppression of the repair process leads to a significant decline in the ability of tumor cells to metastasize and invade other organs. In summary, the FTM@AM nanoplatforms have a highly effective killing and invasion inhibition effect on invasive TNBC mediated by ultrasound, showcasing promising clinical transformation potential.

A Fully Elastic Wearable Electrochemical Sweat Detection System of Tree-Bionic Microfluidic Structure for Real-Time Monitoring.

Fresh sweat contains a diverse range of physiological indicators that can effectively reflect changes in the body. However, existing wearable sweat detection systems face challenges in efficiently collecting and detecting fresh sweat in real-time. Additionally, they often lack the necessary deformation capabilities, resulting in discomfort for the wearer. Here, a fully elastic wearable electrochemical sweat detection system is developed that integrates a sweat-collecting microfluidic chip, a multi-parameter electrochemical sensor, a micro-heater, and a sweat detection elastic circuit board system. The unique tree-bionic structure of the microfluidic chip significantly enhances the efficiency of fresh sweat collection and discharge, enabling real-time detection by the electrochemical sensors. The sweat multi-parameter electrochemical sensor offers high-precision and high-sensitivity measurements of sodium ions, potassium ions, lactate, and glucose. The electronic system is built on an elastic circuit board that matches perfectly to wrinkled skin, ensuring improved wearing comfort and enabling multi-channel data sampling, processing, and wireless transmission. This state-of-the-art system represents a significant advancement in the field of elastic wearable sweat detection and holds promising potential for extending its capabilities to the detection of other sweat markers or various wearable applications.

MnO2 Coated Mesoporous PdPt Nanoprobes for Scavenging Reactive Oxygen Species and Solving Acetaminophen-Induced Liver Injury.

As one of the most widely used drugs, acetaminophen, is the leading cause of acute liver injury. In addition, acetaminophen-induced liver injury (AILI) has a strong relationship with the overproduced reactive oxygen species, which can be effectively eliminated by nanozymes. To address these challenges, mesoporous PdPt@MnO2 nanoprobes (PPM NPs) mimicking peroxide, catalase, and superoxide dismutase-like properties are synthesized. They demonstrate nontoxicity, high colloidal stability, and exceptional reactive oxygen species (ROS)-scavenging ability. By scavenging excessive ROS, decreasing inflammatory cytokines, and inhibiting the recruitment and activation of monocyte/macrophage cells and neutrophils, the pathology mechanism of PPM NPs in AILI is confirmed. Moreover, PPM NPs' therapeutic effect and good biocompatibility may facilitate the clinical treatment of AILI.

Metal-organic frameworks based surface-enhanced Raman spectroscopy technique for ultra-sensitive biomedical trace detection.

Metal-organic frameworks (MOFs) have attracted widespread interest due to their unique and unprecedented advantages in microstructures and properties. Besides, surface-enhanced Raman scattering (SERS) technology has also rapidly developed into a powerful fingerprint spectroscopic technique that can provide rapid, non-invasive, non-destructive, and ultra-sensitive detection, even down to single molecular level. Consequently, a considerable amount of researchers combined MOFs with the SERS technique to further improve the sensing performance and broaden the applications of SERS substrates. Herein, representative synthesis strategies of MOFs to fabricate SERS-active substrates are summarized and their applications in ultra-sensitive biomedical trace detection are also reviewed. Besides, relative barriers, advantages, disadvantages, future trends, and prospects are particularly discussed to give guidance to relevant researchers.

Two-Photon Nanoprobe for NIR-II Imaging of Tumour and Biosafety Evaluation.

How to develop near-infrared second window (NIR-II, 1000-1700 nm) fluorescent nanoprobes with a uniform size, strong fluorescence signal and good biosafety owns great clinical requirement. Herein we reported that a two photon fluorescent nanoprobe was developed via encapsulating NIR-II-fluorescent molecules into DSPE-PEG, which was effectively endocytosized by cancer cells, and achieved strong NIR-II fluorescence imaging in cancer cells and cancer cell-beard mice models. Prepared NIR-II-fluorescent nanoprobe exhibited rapid metabolism and excellent biocompatibility. In conclusion, the prepared two photon nanoprobe owns good biosafety, and clinical translational prospect in NIR-II fluorescent imaging of tumour in vivo in near future.

Tumor microenvironment pH-responsive pentagonal gold prism-based nanoplatform for multimodal imaging and combined therapy of castration-resistant prostate cancer.

Given that there is lack of effective therapies for castration-resistant prostate cancer (CRPC), the combination of photothermal (PTT), photodynamic (PDT), and chemical therapy (CT) has emerged as a prominent strategy. Tumor-targeted delivery and controlled release of antitumor drug are key-elements of any combined therapy. Considering these important elements, we designed and constructed tumor microenvironment (TME)-activated nanoprobes (PGP/CaCO3@IR820/DTX-HA). The CaCO3 shell could efficiently entrap the photosensitizer IR820 and the chemotherapeutic docetaxel (DTX) on the surface of pentagonal gold prisms (PGPs) to prevent elimination from the circulation, and it could act as a TME-trigger to achieve TME-responsive drug release. After modification with hyaluronic acid, PGP/CaCO3@IR820/DTX-HA was capable of synergistic TME-triggered PTT/PDT/CT and tumor-targeted delivery. Our in vitro and in vivo studies demonstrate that PGP/CaCO3@IR820/DTX-HA could achieve synergistic antitumor effects following near-infrared (NIR)-light irradiation. In addition, using the NIR fluorescence signal from IR820 and the photoacoustic (PA) signal from PGPs, i.e., through multimodal fluorescence/photoacoustic imaging, we could monitor the in vivo distribution and excretion of PGP/CaCO3@IR820/DTX-HA. Therefore, it can be concluded that PGP/CaCO3@IR820/DTX-HA shows promising clinical translational potential as a treatment for CRPC. STATEMENT OF SIGNIFICANCE: Utilizing pentagonal gold prisms (PGPs), we constructed a multifunctional nanoplatform (PGP/CaCO3@IR820/DTX-HA) for effectively delivering agents into the tumor microenvironment (TME) for the diagnosis and therapy of castration-resistant prostate cancer (CRPC). The synthetic nanoplatform can satisfy TME-activated synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemical therapy (CT) and NIR fluorescence imaging/photoacoustic (PA) imaging. Hyaluronic acid (HA) on the surface of nanoplatform allowed the specific tumor-targeting capacity and biocompatibility. In conclusion, PGP/CaCO3@IR820/DTX-HA could be a promising integrated nanoplatform for CRPC diagnosis and treatment.

Metal-organic framework engineered corn-like SERS active Ag@Carbon with controllable spacing distance for tracking trace amount of organic compounds.

Probing water-soluble organic compounds via Surface-enhanced Raman scattering (SERS) technique could be helpful to prevent harmful impacts of polluted water. A key limitation of restraining SERS technique in probing these pollutants is the difficulty to control the spacing distance of plasmonic nanoparticles within 10 nm so that SERS effect can be efficiently induced. Herein, a strategy of mass-producing Ag-based SERS active material with tunable spacing distance is reported. In brevity, metal-organic framework (MOF) engineered corn-like Ag@Carbon is synthesized by simply thermal treating Ag-MOF. The thermal treatment in-situ turns Ag+ into Ag nanoparticles (NPs), resulting in Ag NPs well-dispersed on the surface of the carbonized MOF and forming ordered SERS hotspots. Due to the spatial distance of Ag+ directly depends on the molecular diameter of MOF organic ligands, spacing distance of Ag NP is fixed at around 7 nm. Theoretical analysis and experimental study confirm that the uniformly distributed Ag NPs lead to desirable SERS activity. Further study evidences the presented corn-like Ag@Carbon could be a good candidate for tacking organic compounds with satisfactory sensitivity, specificity and low detection limit (10-8 M). Conclusively, these impressive results indicate a bright future of adopting the proposed strategy to design future SERS active materials.

Ultra-homogeneous NIR-II fluorescent self-assembled nanoprobe with AIE properties for photothermal therapy of prostate cancer.

Near-infrared two-zone (NIR-II) fluorescence imaging has attracted attention as a non-invasive imaging technology that provides centimeter-level depth and micron-level resolution. However, producing a NIR-II fluorescent nanoprobe with uniform size, high bio-identical capacity, and fluorescence intensity, while being metabolizable in vivo, remains a challenge. We first produce a hydrophobic NIR-II fluorescent molecule with AIE properties, and subject it to ultrasonic and extrusion treatments to generate a DSPE-PEG-encapsulated NIR-II nanoprobe with an ultra-homogeneous particle size. The current study based on in vitro and mouse tumor-bearing model-based experiments indicate that cancer cells could efficiently take up this nanoprobe, which aggregates in tumor tissues, is susceptible to metabolization, and enables ideal photothermal therapeutic effects. Thus, this NIR-II nanoprobe with AIE properties shows great potential for precise clinical diagnosis and treatment of cancer.

Topology Selectivity in On-Surface Dehydrogenative Coupling Reaction: Dendritic Structure versus Porous Graphene Nanoribbon.

Selective control on the topology of low-dimensional covalent organic nanostructures in on-surface synthesis has been challenging. Herein, with combined scanning tunneling microscopy (STM) and X-ray photoelectron spectroscopy (XPS), we report a successful topology-selective coupling reaction on the Cu(111) surface by tuning the thermal annealing procedure. The precursor employed is 1,3,5-tris(2-bromophenyl)benzene (TBPB), for which Ullmann coupling is impeded due to the intermolecular steric hindrance. Instead, its chemisorption on the Cu(111) substrate has triggered the ortho C-H bond activation and the following dehydrogenative coupling at room temperature (RT). In the slow annealing experimental procedure, the monomers have been preorganized by their self-assembly at RT, which enhances the formation of dendritic structures upon further annealing. However, the chaotic chirality of dimeric products (obtained at RT) and hindrance from dense molecular island make the fabrication of high-quality porous two-dimensional nanostructures difficult. In sharp contrast, direct deposition of TBPB molecules on a hot surface led to the formation of ordered porous graphene nanoribbons and nanoflakes, which is confirmed to be the energetically favorable reaction pathway through density functional theory-based thermodynamic calculations and control experiments. This work demonstrates that different thermal treatments could have a significant influence on the topology of covalent products in on-surface synthesis and presents an example of the negative effect of molecular self-assembly to the ordered covalent nanostructures.

Selective Synthesis of Conjugated Chiral Macrocycles: Sidewall Segments of (-)/(+)-(12,4) Carbon Nanotubes with Strong Circularly Polarized Luminescence.

Carbon nanotubes (CNTs) have unusual physical properties that are valuable for nanotechnology and electronics, but the chemical synthesis of chirality- and diameter-specific CNTs and π-conjugated CNT segments is still a great challenge. Reported here are the selective syntheses, isolations, characterizations, and photophysical properties of two novel chiral conjugated macrocycles ([4]cyclo-2,6-anthracene; [4]CAn2,6 ), as (-)/(+)-(12,4) carbon nanotube segments. These conjugated macrocyclic molecules were obtained using a bottom-up assembly approach and subsequent reductive elimination reaction. The hoop-shaped molecules can be directly viewed by a STM technique. In addition, chiral enantiomers with (-)/(+) helicity of the [4]CAn2,6 were successfully isolated by HPLC. The new tubular CNT segments exhibit large absorption and photoluminescence redshifts compared to the monomer unit. The carbon enantiomers are also observed to show strong circularly polarized luminescence (glum ≈0.1). The results reported here expand the scope of materials design for bottom-up synthesis of chiral macrocycles and enrich existing knowledge of their optoelectronic properties.

Synthesis of Giant π-Extended Molecular Macrocyclic Rings as Finite Models of Carbon Nanotubes Displaying Enriched Size-Dependent Physical Properties.

Bottom-up synthesis of π-extended macrocyclic carbon rings is promising for constructing length- and diameter-specific carbon nanotubes (CNTs). However, it is still a great challenge to realize size-controllable giant carbon macrocycles. Herein, a tunable synthesis of curved nanographene-based giant π-extended macrocyclic rings (CHBC[n]s; n=8, 6, 4), as finite models of armchair CNTs, is reported. Among them, CHBC[8] contains 336 all-carbon atoms and is the largest cyclic conjugated molecular CNT segment ever reported. CHBC[n]s were systematically characterized by various spectroscopic methods and applied in photoelectrochemical cells for the first time. This revealed that the proton chemical shifts, fluorescence, and electronic and photoelectrical properties of CHBC[n]s are highly dependent on the macrocycle diameter. The tunable bottom-up synthesis of giant macrocyclic rings could pave the way towards large π-extended diameter- and chirality-specific CNT segments.

Through-space π-delocalization in a conjugated macrocycle consisting of [2.2]paracyclophane.

Herein, we report the synthesis and characterization of a [2.2]paracyclophane-containing macrocycle (PCMC) as a new through-space conjugated macrocycle using only benzene groups as the skeleton. For comparison, a diphenylmethane-containing nanohoop macrocycle (DCMC) with a non-conjugated linker was also synthesized. Their structures were confirmed by NMR and HR-MS, and their photophysical properties were studied by UV-vis and fluorescence spectroscopies combined with theoretical calculations. The strain energy of PCMC was estimated to be as high as 72.58 kcal mol-1.

From Planar Macrocycle to Cylindrical Molecule: Synthesis and Properties of a Phenanthrene-Based Coronal Nanohoop as a Segment of [6,6]Carbon Nanotube.

Herein, we explore phenanthrene as the building block to synthesize a hoop-shaped [6,6]carbon nanotube segment from a planar macocycle via a Diels-Alder reaction. The phenanthrene-based coronal nanohoop 7 was fully characterized by HR-MS, NMR, and other spectroscopies. In addition, its photophysical properties and the supramolecular interactions between 7 and fullerene C60 were investigated. This present work suggests an easily accessible Diels-Alder reaction strategy to synthesize cylindrical nanohoops.

Photoconductive Curved-Nanographene/Fullerene Supramolecular Heterojunctions.

This study presents synthesis and characterizations of two novel curved nanographenes that strongly bind with fullerene C60 to form photoconductive heterojunctions. Films of the self-assembled curved nanographene/fullerene complexes, which served as the photoconductive layer, generated a significant photocurrent under light irradiation. Gram-scale quantities of these curved nanographenes (TCR and HCR) as the "crown" sidewalls can be incorporated into a carbon nanoring to form molecular crowns, and the molecular structure of C60 @TCR is determined by single-crystal X-ray diffraction. The UV/Vis absorption and emission spectra, and theoretical studies revealed their unique structural features and photophysical properties. Time-resolved spectroscopic results clearly suggest fast photoinduced electron transfer process in the supramolecular heterojunctions.

A Three-Dimensional Capsule-like Carbon Nanocage as a Segment Model of Capped Zigzag [12,0] Carbon Nanotubes: Synthesis, Characterization, and Complexation with C70.

Herein we report the synthesis and photophysical and supramolecular properties of a novel three-dimensional capsule-like hexa-peri-hexabenzocoronene (HBC)-containing carbon nanocage, tripodal-[2]HBC, which is the first synthetic model of capped zigzag [12,0] carbon nanotubes (CNTs). Tripodal-[2]HBC was synthesized by the palladium-catalyzed coupling of triboryl hexabenzocoronene and L-shaped cyclohexane units, followed by nickel-mediated C-Br/C-Br coupling and subsequent aromatization of the cyclohexane moieties. The physical properties of tripodal-[2]HBC and its supramolecular host-guest interaction with C70 were further studied by UV/Vis and fluorescence spectroscopy. Theoretical calculations revealed that the strain energy of tripodal-[2]HBC was as high as 55.2 kcal mol-1 .

Facile three-step synthesis and photophysical properties of [8]-, [9]-, and [12]cyclo-1,4-naphthalene nanorings via platinum-mediated reductive elimination.

Herein we report a facile three-step synthesis of [8]-, [9]-, and [12]cyclo-1,4-naphthalene nanorings as the conjugated segments of carbon nanotubes. The nanorings were created via a platinum-mediated assembly of 1,4-naphthalene-based units and subsequent reductive elimination in the presence of triphenylphosphine. This present platinum-mediated approach is attractive because of its simple three-step process to produce the targeted nanorings in a high overall yield. In addition, their photophysical properties were studied using UV-vis spectroscopy and photoluminescence (PL) spectroscopy, which further revealed their unique size-dependent properties.