Modulating nanostructures with polyvinylpyrrolidone: Design and development of a porous, biocompatible, and pH-Stable core-shell magnetic microrobot for demonstrating drug absorption from wastewater.

Increased antineoplastic drug concentrations in wastewater stem from ineffective treatment plants and increased usage. Although microrobots are promising for pollutant removal, they face hurdles in developing a superstructure with superior adsorption capabilities, biocompatibility, porosity, and pH stability. This study focused on adjusting the PVP concentration from 0.05 to 0.375 mM during synthesis to create a favorable CMOC structure for drug absorption. Lower PVP concentrations (0.05 mM) yielded a three-dimensional nanoflower structure of CaMoO4 and CuS nanostructures, whereas five-fold concentrations (0.25 mM) produced a porous structure with a dense CuS core encased in a transparent CaMoO4 shell. The magnetically movable and pH-stable COF@CMOC microrobot, achieved by attaching CMOC to cobalt ferrite (CoF) NPs, captured doxorubicin efficiently, with up to 57 % efficiency at 200 ng/mL concentration for 30 min, facilitated by electrostatic interaction, hydrogen bonding, and pore filling of DOX. The results demonstrated that DOX removal through magnetic motion showed superior performance, with an estimated improvement of 57% compared to stirring conditions (17 %). A prototype PDMS microchannel system was developed to study drug absorption and microrobot recovery. The CaMoO4 shell of the microrobots exhibited remarkable robustness, ensuring long-lasting functionality in harsh wastewater environments and improving biocompatibility while safeguarding the CuS core from degradation. Therefore, microrobots are a promising eco-friendly solution for drug extraction. These microrobots show promise for the selective removal of doxorubicin from contaminated wastewater.

A self-assembled three-dimensional hierarchical nanoflower: an efficient enzyme-mimetic material for cancer cell detection that improves ROS generation for therapy.

Three-dimensional (3D) nanomaterials with high functional properties are emerging as the most promising artificial enzymes for overcoming the significant disadvantages of natural enzymes. Anticancer therapy using 3D-enzyme mimetic materials has emerged as an essential development for catalyzing cancer cell destruction. We report for the first time a novel 3D-based enzyme mimetic material, CaMoO4/MoS2/CuS nanoflower (CMC NF), that exhibits a large specific surface area, uniform flower-like structure, excellent biocompatibility, and high porosity, making it a suitable candidate for cancer detection and therapy. Additionally, CMC NFs were conjugated with folic acid (FA) to selectively target cancer cells, resulting in FA-CMC NFs explicitly binding to overexpressed folate receptor alpha (FRα) in MDA-MB-231 cells. Based on the peroxidase activity, the FA-CMC NFs are an effective nanoprobe for the selective detection of MDA-MB-231 cells over a wide detection range (50 to 5.5 × 104 cells per mL) with a low limit of detection (LOD) value of 10 cells per mL. In addition to their cancer detection capability, the FA-CMC NFs also effectively generated ˙OH radicals in a concentration-dependent manner to treat cancer cells. Under light conditions, the FA-CMC NFs with H2O2 solution showed efficient degradation of methylene blue (MB) dye, and the solution color appeared to fade within 15 min, indicating that they generated ˙OH radicals, which can efficiently kill cancer cells. Thus, the superior functionality of FA-CMC NFs offers cost-effective, facile, and reliable cancer cell detection, providing a new treatment option for cancer treatment and diagnosis.

A dual stimuli-responsive smart soft carrier using multi-material 4D printing.

This paper proposes a 4D printed smart soft carrier with a hemispherical hollow and openable lid. The soft carrier is composed of a lid with a slot (with a shape of 4 legs), a border, and a hemisphere. The soft carrier is fabricated by 4D printing using smart hydrogels. Specifically, the lid, border, and hemisphere are fabricated using a thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel, a non-responsive polyethylene glycol (PEG) hydrogel with superparamagnetic iron oxide nanoparticles (SPIONs), and a PEG hydrogel, respectively. Since the SPIONs are included in the border, the slot in the center of the lid is opened and closed according to the temperature change caused by near-infrared (NIR) irradiation, and the proposed soft carrier is magnetically driven by an external magnetic field. The hemisphere enables the storage and transport of cargo. The proposed soft carrier can control the opening and closing of the slot and movement to a desired position in water. Several cargo delivery experiments were conducted using various shapes and numbers of cargo. In addition, the proposed soft carrier can successfully handle small living marine organisms. This soft carrier can be manufactured by 4D printing and operated by dual stimuli (NIR and magnetic field) and can safely deliver various types of cargo and delicate organisms without leakage or damage. The flexibility of 4D printing enables the size of the soft carrier to be tailored to the specific physical attributes of various objects, making it an adaptable and versatile delivery approach.

Magnetically Actuated Helical Microrobot with Magnetic Nanoparticle Retrieval and Sequential Dual-Drug Release Abilities.

Cancer is one of the diseases with high mortality worldwide. Various methods for cancer treatment are being developed, and among them, magnetically driven microrobots capable of minimally invasive surgery and accurate targeting are in the spotlight. However, existing medical magnetically manipulated microrobots contain magnetic nanoparticles (MNPs), which can cause toxicity to normal cells after the delivery of therapeutic drugs. In addition, there is a limitation in that cancer cells become resistant to the drug by mainly delivering only one drug, thereby reducing the treatment efficiency. In this paper, to overcome these limitations, we propose a microrobot that can separate/retrieve MNPs after precise targeting of the microrobot and can sequentially deliver dual drugs (gemcitabine (GEM) and doxorubicin (DOX)). First, after the proposed microrobot targeting, MNPs attached to the microrobot surface can be separated from the microrobot using focused ultrasound (FUS) and retrieved through an external magnetic field. Second, the active release of the first conjugated drug GEM to the surface of the microrobot is possible using near-infrared (NIR), and as the microrobot slowly decomposes over time, the release of the second encapsulated DOX is possible. Therefore, it is possible to increase the cancer cell treatment efficiency with sequential dual drugs in the microrobot. We performed basic experiments on the targeting of the proposed magnetically manipulated microrobot, separation/retrieval of MNPs, and the sequential dual-drug release and validated the performances of the microrobot through in vitro experiments using the EMA/FUS/NIR integrated system. As a result, the proposed microrobot is expected to be used as one of the methods to improve cancer cell treatment efficiency by improving the limitations of existing microrobots in cancer cell treatment.

Tumor-targeted molybdenum disulfide@barium titanate core-shell nanomedicine for dual photothermal and chemotherapy of triple-negative breast cancer cells.

Combinational therapy can improve the effectiveness of cancer treatment by overcoming individual therapy shortcomings, leading to accelerated cancer cell apoptosis. Combinational cancer therapy is attained by a single nanosystem with multiple physicochemical properties providing an efficient synergistic therapy against cancer cells. Herein, we report a folate receptor-targeting dual-therapeutic (photothermal and chemotherapy) core-shell nanoparticle (CSNP) exhibiting a molybdenum disulfide core with a barium titanate shell (MoS2@BT) to improve therapeutic efficacy against triple-negative breast cancer (TNBC) MDA-MB-231 cells. A simple hydrothermal approach was used to achieve the MoS2@BT CSNPs, and their diameter was calculated to be approximately 180 ± 25 nm. In addition to improving the photothermal efficiency and stability of the MoS2@BT CSNPs, their surface was functionalized with polydopamine (PDA) and subsequently modified with folic acid (FA) to achieve enhanced tumour-targeting CSNPs, named MoS2@BT-PDA-FA (MBPF). Then, gemcitabine (Gem) was loaded into the MBPF, and its loading and releasing efficacy were calculated to be 17.5 wt% and 64.5 ± 3%, respectively. Moreover, the photothermal conversion efficiency (PCE) of MBPF was estimated to be 35.3%, and it also showed better biocompatibility, which was determined by an MTT assay. The MBPF significantly increased the ambient temperature to 56.3 °C and triggered Gem release inside the TNBC cells when exposed to a near-infrared (NIR) laser (808 nm, 1.5 W cm-2, 5 min). Notably, the MoS2@BT-based nanosystem was used as a photothermal agent and a therapeutic drug-loading container for combating TNBC cells. Benefiting from the combined therapy, MBPF reduced TNBC cell viability to 81.3% due to its efficient synergistic effects. Thus, the proposed tumour-targeting MoS2@BT CSNP exhibits high drug loading, better biocompatibility, and improved anticancer efficacy toward TNBC cells due to its dual therapeutic approach in a single system, which opens up a new approach for dual cancer therapy.

Study on Intention Recognition and Sensory Feedback: Control of Robotic Prosthetic Hand Through EMG Classification and Proprioceptive Feedback Using Rule-based Haptic Device.

In this study, for intention recognition, a convolutional neural network (CNN) classification model using the electromyography (EMG) signals acquired from the subject was developed. For sensory feedback, a rule-based wearable proprioceptive feedback haptic device, a new method for providing feedback on the grip information of a robotic prosthesis was proposed. Then, we constructed a closed-loop integrated system consisting of the CNN-based EMG classification model, the proposed haptic device, and a robotic prosthetic hand. Finally, an experiment was conducted in which the closed-loop integrated system was used to simultaneously evaluate the performance of the intention recognition and sensory feedback for a subject. The trained EMG classification model and the proposed haptic device showed the intention recognition and sensory feedback performance with 97% or higher accuracy in 10 grip states. Although some errors occurred in the intention recognition using the EMG classification model, in general, the grip intention of the subject was grasped relatively accurately, and the grip pattern was also accurately transmitted to the subject by the proposed haptic device. The integrated system which consists of the intention recognition using the CNN-based EMG classification model and the sensory feedback using the proposed haptic device is expected to be utilized for robotic prosthetic hand prosthesis control of limb loss participants.

Enhanced sensing and electrical performance of hierarchical porous ionic polymer-metal nanocomposite via minimizing cracks in electrode.

High-performance foldable metal-coated ionic polymer-metal nanocomposites (IPMNCs) with crack minimized electrode are desired for wearable electronics, energy harvesting devices, tactile sensors, structural health monitors, humidity sensors, and supercapacitor devices. However, the IPMNC shows the cracked structure that seriously decreases the performance of IPMNCs for sensors and actuators applications. To overcome the issue of the cracked metal electrode, here we propose a metal-coated hierarchical porous structured IPMNC via minimizing the cracks in the Platinum (Pt) electrode using attachment of poly(2-acrylamide-2-methyl-1-propane-sulfonic acid) (PAMPS) in poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE))/polyvinylpyrrolidone (PVP) blend. The crack-minimized Pt electrode deposition on PAMPS attached P(VDF-TrFE)/PVP-based IPMNCs showed enhanced electrical and sensing signals compared to the Nafion, ionic liquid, and polystyrene sulphonic acid-based IPMNCs. The developed IPMNCs with an optimized composition depict stable sensing signals up to 10,000 cycles. The hierarchical porous structure and the crack-minimized metal electrode on the P(VDF-TrFE)/PVP/PAMPS IPMNC can be utilized in various attractive applications such as energy harvesting, wearable electronics, humidity sensor, pulse, braille recognition, catalyst supports, bio-interfacing, and sensors.

Magnetism-controlled assembly of composite stem cell spheroids for the biofabrication of contraction-modulatory 3D tissue.

Biofabrication of organ-like engineered 3D tissue through the assembly of magnetized 3D multi-cellular spheroids has been recently investigated in tissue engineering. However, the cytotoxicity of magnetic nanoparticles (MNPs) and contraction-induced structural deformation of the constructs have been major limitations. In this study, we developed a method to fabricate composite stem cell spheroids using MNP-coated fibers, alleviating MNP-mediated toxicity and controlling structural assembly under external magnetic stimuli. The MNP-coated synthetic fibers (MSFs) were prepared by coating various amounts of MNPs on the fibers via electrostatic interactions. The MSFs showed magnetic hysteresis and no cytotoxicity on 2D-cultured adipose-derived stem cells (ADSCs). The composite spheroids containing MSFs and ADSCs were rapidly formed in which the amount of impregnated MSFs modulated the spheroid size. The fusion ofin vitrocomposite spheroids was then monitored at the contacting interface; the fused spheroids with over 10µg of MSF showed minimal contraction after 7 d, retaining around 90% of total area ratio regardless of the number of cells, indicating that the presence of fibers within the composite spheroid supported its structural maintenance. The fusion of MSF spheroids was modulated by external magnetic stimulation, and the effect of magnetic force on the movement and fusion of the spheroids was investigated using COMSOL simulation. Finally, ring and lamellar structures were successfully assembled using remote-controlled MSF spheroids, showing limited deformation and high viability up to 50 d duringin vitroculture. In addition, the MSFs demonstrated no adverse effects on ADSC osteochondral differentiation. Altogether, we envision that our magnetic assembly system would be a promising method for the tissue engineering of structurally controlled organ-like constructs.

Exosome-based hybrid nanostructures for enhanced tumor targeting and hyperthermia therapy.

Recently, natural exosomes have attracted attention as an ideal drug carrier to overcome the limitations of existing drug delivery systems which are toxicity induction and low cancer-targeting performance. In this study, we propose an exosome-based hybrid nanostructure (EHN) with improved targeting ability and therapeutic efficacy against colorectal cancer by using exosomes isolated from the tumor cell line as a drug carrier. The proposed EHN can have high biocompatibility by using exosomes, a biologically derived material, and show improved targeting performance by adding a tumor-targeting ligand (folic acid). In addition, the proposed EHN is capable of chemotherapy because doxorubicin, an anticancer drug, is encapsulated by the exosome with high efficiency, and it can induce hyperthermia therapy because of the magnetic nanoparticles (MNPs) attached to the surface of exosomes. Through in vitro and in vivo experiments using a xenograft tumor mouse model, it was confirmed that the proposed EHN could exhibit increased apoptosis and excellent tumor growth inhibition ability. Therefore, the proposed EHN is expected to overcome the limitations of existing drug delivery systems and be utilized as an effective drug delivery system in cancer treatment.

Magnetically Actuated Drug Delivery Helical Microrobot with Magnetic Nanoparticle Retrieval Ability.

Therapeutic drug delivery microrobots capable of accurate targeting using an electromagnetic actuation (EMA) system are being developed. However, these drug delivery microrobots include a large number of magnetic nanoparticles (MNPs) for accurate EMA targeting, which causes side effects, such as problems with membrane integrity and normal cell apoptosis. Here, a biocompatible and hydrolyzable PEGDA-based drug delivery helical microrobot capable of MNP retrieval is proposed in which doxorubicin (DOX), an anticancer drug, is encapsulated and MNPs are conjugated by a disulfide bond. After being accurately delivered to the lesion of cancer cells through magnetic field manipulation, the fabricated microrobot provides rapid MNP separation and retrieval from the microrobot because of the use of dithiothreitol (DTT), a reducing agent, as an environment similar to the surrounding cancer cells and near-infrared (NIR) as an external stimulus. The characteristics of the fabricated microrobot are analyzed, and fundamental tests for active electromagnetic field manipulation, separation/retrieval of MNPs from the microrobot, and its hydrolysis are discussed. The therapeutic performance of the fabricated microrobot is verified through an in vitro test using tumor cells. Consequently, by use of an integrated system of microscope, eight-coil EMA, and NIR it is shown that the proposed microrobot can be moved to the target site by electromagnetic manipulation. The MNPs conjugated to the microrobot can be separated and retrieved, and the therapeutic effect on tumor cells by the encapsulated drug can be seen.

Active delivery of multi-layer drug-loaded microneedle patches using magnetically driven capsule.

In this paper, we propose the active delivery of multi-layer drug-loaded microneedle (MN) patches using a capsule that can be driven by an external magnetic field. Firstly, the multi-layer drug-loaded MN patches consist of three delivered MN patches which are composed of a drug-loaded MN patch and polydimethylsiloxane layer. The drug-loaded MN patch is made of a 10% gelatin solution and a drug. The multi-layer MN patches are attached to a permanent magnet in a magnetically driven capsule. Under an external magnetic field generated by an electromagnetic actuation system, the capsule with the multi-layer MN patches can reach the target lesions, and each MN patch can be delivered to the target lesions for medical treatment. The active delivery of the multi-layer MN patches using the proposed magnetically driven capsule was confirmed via phantom experiments. Accordingly, the adhesion of the three separated faces of the multi-layer MN patches and the adhesion between the porcine small intestine and the MN patch were measured using a load cell. We demonstrate the feasibility of the active delivery of the multi-layer MN patches to the target lesions on a porcine small intestine. Consequently, we expect that the active delivery of the multi-layer drug-loaded MN patches using the magnetically driven capsule presented in this study can be a useful method for drug delivery to lesions at various locations in the gastrointestinal tract.

Bilayer Hydrogel Sheet-Type Intraocular Microrobot for Drug Delivery and Magnetic Nanoparticles Retrieval.

By virtue of minimum invasiveness and driving ability using a magnetic field, drug delivery with the aid of a microrobot has an inherent potential for targeted treatment for the eye. The use of microrobots, however, has the limitation of leaving magnetic nanoparticles (MNPs) in the eye that can cause side effects. In this study, a bilayer hydrogel microrobot capable of retrieving MNPs after drug delivery is proposed that overcomes the limitations of existing microrobots. The bilayer hydrogel microrobot is composed of an MNPs layer and a therapeutic layer. Upon applying an alternating magnetic field (AMF) at the target point, the therapeutic layer is dissolved to deliver drug particles, and then the MNPs layer can be retrieved using a magnetic field. The targeting and MNPs retrieval tests validate the drug delivery and MNPs retrieval ability of the microrobot. The ex vivo bovine vitreous and in vitro cell tests demonstrate the potential for the vitreous migration of the microrobot and the therapeutic effect against retinoblastoma Y79 cancer cells. This bilayer hydrogel sheet-type intraocular microrobot provides a new drug delivery paradigm that overcomes the limitations of microrobot by maintaining the advantages of conventional microrobots in delivering drugs to the eye and retrieving MNPs after drug delivery.

Targeted removal of leukemia cells from the circulating system by whole-body magnetic hyperthermia in mice.

Until now, magnetic hyperthermia was used to remove solid tumors by targeting magnetic nanoparticles (MNPs) to tumor sites. In this study, leukemia cells in the bloodstream were directly removed by whole-body hyperthermia, using leukemia cell-specific MNPs. An epithelial cellular adhesion molecule (EpCAM) antibody was immobilized on the surface of MNPs (EpCAM-MNPs) to introduce the specificity of MNPs to leukemia cells. The viability of THP1 cells (human monocytic leukemia cells) was decreased to 40.8% of that in control samples by hyperthermia using EpCAM-MNPs. In AKR mice, an animal model of lymphoblastic leukemia, the number of leukemia cells was measured following the intravenous injection of EpCAM-MNPs and subsequent whole-body hyperthermia treatment. The result showed that the leukemia cell number was also decreased to 43.8% of that without the treatment of hyperthermia, determined by Leishman staining of leukemia cells. To support the results, simulation analysis of heat transfer from MNPs to leukemia cells was performed using COMSOL Multiphysics simulation software. The surface temperature of leukemia cells adhered to EpCAM-MNPs was predicted to be increased to 82 °C, whereas the temperature of free cells without adhered MNPs was predicted to be 38 °C. Taken together, leukemia cells were selectively removed by magnetic hyperthermia from the bloodstream, because EpCAM-modified magnetic particles were specifically attached to leukemia cell surfaces. This approach has the potential to remove metastatic cancer cells, and pathogenic bacteria and viruses floating in the bloodstream.

Multifunctional Nanorobot System for Active Therapeutic Delivery and Synergistic Chemo-photothermal Therapy.

Nanorobots are safe and exhibit powerful functionalities, including delivery, therapy, and diagnosis. Therefore, they are in high demand for the development of new cancer therapies. Although many studies have contributed to the progressive development of the nanorobot system for anticancer drug delivery, these systems still face some critical limitations, such as potentially toxic materials in the nanorobots, unreasonable sizes for passive targeting, and the lack of several essential functions of the nanorobot for anticancer drug delivery including sensing, active targeting, controlling drug release, and sufficient drug loading capacity. Here, we developed a multifunctional nanorobot system capable of precise magnetic control, sufficient drug loading for chemotherapy, light-triggered controlled drug release, light absorption for photothermal therapy, enhanced magnetic resonance imaging, and tumor sensing. The developed nanorobot system exhibits an in vitro synergetic antitumor effect of photothermal therapy and chemotherapy and outstanding tumor-targeting efficiency in both in vitro and in vivo environments. The results of this study encourage further explorations of an efficient active drug delivery system for cancer treatment and the development of nanorobot systems for other biomedical applications.

Preliminary study on alginate/NIPAM hydrogel-based soft microrobot for controlled drug delivery using electromagnetic actuation and near-infrared stimulus.

Currently, microrobots are receiving attention because of their small size and motility, which can be applied to minimal invasive therapy. Additionally, various microrobots using hydrogel with the characteristics of biocompatibility and biodegradability are also being developed. Among them, microrobots that swell and deswell in response to temperature changes caused by external near infrared (NIR) stimuli, focused ultrasound, and an alternating magnetic field, have been receiving a great amount of interest as drug carriers for therapeutic cell delivery. In this study, we propose a spring type medical microrobot that can be manipulated by an electromagnetic actuation (EMA) system and respond to an external stimulus (NIR). Additionally, we verified its feasibility with regard to targeting and drug delivery. There exist various methods of fabricating a spring type microrobot. In this study, we adopted a simple method that entails using a perfluoroalkoxy (PFA) microtube and a syringe pump. Moreover, we also used a hydrogel mixture composed of natural alginate, N-Isopropylacrylamide (NIPAM) for temperature responsiveness, and magnetic nanoparticles (MNPs) for electromagnetic control. Then, we fabricated a spring type alginate/NIPAM hydrogel-based soft microrobot. Additionally, we encapsulated doxorubicin (DOX) for tumor therapy in the microrobot. To verify the feasibility of the proposed spring type hydrogel-based soft microrobot's targeting and drug delivery, we developed an EMA and NIR integrated system. Finally, we observed the swelling and deswelling of the soft microrobot under NIR stimulation and verified the EMA controlled targeting. Moreover, we implemented a control function to release the encapsulated anticancer drug (DOX) through the swelling and deswelling of the soft microrobot by NIR, and evaluated the feasibility of cancer cell therapy by controlling the release of the drug from the soft microrobot.

Real-time microrobot posture recognition via biplane X-ray imaging system for external electromagnetic actuation.

PURPOSE: As a promising intravascular therapeutic approach for autonomous catheterization, especially for thrombosis treatment, a microrobot or robotic catheter driven by an external electromagnetic actuation system has been recently investigated. However, the three-dimensional (3D) real-time position and orientation tracking of the microrobot remains a challenge for precise feedback control in clinical applications owing to the micro-size of the microrobot geometry in vessels, along with bifurcation and vulnerability. Therefore, in this paper, we propose a 3D posture recognition method for the unmanned microrobotic surgery driven by an external electromagnetic actuator system. METHODS: We propose a real-time position and spatial orientation tracking method for a millimeter-sized intravascular object or microrobot using a principal component analysis algorithm and an X-ray reconstruction. The suggested algorithm was implemented to an actual controllable wireless microrobot system composed of a bullet-shaped object, a biplane X-ray imaging device, and an electromagnetic actuation system. Numerical computations and experiments were conducted for the performance verification. RESULTS: The experimental results showed a good performance of the implemented system with tracking errors less than 0.4 mm in position and 2° in orientation. The proposed tracking technique accomplished a fast processing time, ~ 0.125 ms/frame, and high-precision recognition of the micro-sized object. CONCLUSIONS: Since the suggested method does not require pre-information of the object geometry in the human body for its 3D shape and position recognition, it could be applied to various elliptical shapes of the microrobot system with computation time efficacy and recognition accuracy. Hence, the method can be used for therapeutic millimeter- or micron-sized manipulator recognition in vascular, as well as implanted objects in the human body.

Dual tumor-targeted multifunctional magnetic hyaluronic acid micelles for enhanced MR imaging and combined photothermal-chemotherapy.

Multifunctional polymeric micelles were developed as a promising dual tumor-targeted drug delivery platform for magnetic resonance (MR) imaging and combined photothermal-chemotherapy. HA-C16 copolymers were synthesized via peptide formation process with subsequent co-encapsulation of therapeutic agent docetaxel (DTX) and superparamagnetic iron oxide nanoparticles (SPIONs) to form the multifunctional micelles. The micelles exhibited uniform nanosize and remarkable colloidal stability in aqueous solution. The sustained drug release behavior from HA micelles was observed over the test period. Moreover, the specific targeting capability based on CD44 recptor-mediated endocytosis and the enhanced targeting efficacy by in presence of external magnetic field were investigated. The clustered SPIONs within micelles exerted excellent contrast effect with high r2 relaxivity in MR phantom test. Furthermore, the multifunctional micelles could readily convert light to heat to hyperthermia temperature upon near infrared light irradition and induce photothermal ablation to breast cancer cells. The combined photothermal therapy with DTX-mediated chemotherapy of the developed multifunctional polymeric micells could generate a synergistic therapeutic effect. Based on these findings, the resulting multifunctional micelles may provide high potential for multimodality theragnosis of cancer.

Folate-receptor-targeted NIR-sensitive polydopamine nanoparticles for chemo-photothermal cancer therapy.

We propose the use of folate-receptor-targeted, near-infrared-sensitive polydopamine nanoparticles (NPs) for chemo-photothermal cancer therapy as an enhanced type of drug-delivery system which can be synthesized by in situ polymerization and conjugation with folic acid. The NPs consist of a Fe3O4/Au core, coated polydopamine, conjugated folic acid, and loaded anti-cancer drug (doxorubicin). The proposed multifunctional NPs show many advantages for therapeutic applications such as good biocompatibility and easy bioconjugation. The polydopamine coating of the NPs show a higher photothermal effect and thus more effective cancer killing compared to Fe3O4/Au nanoparticles at the same intensity as near-infrared laser irradiation. In addition, the conjugation of folic acid was shown to enhance cancer cellular uptake efficiency via the folate receptor and thus improve chemotherapeutic efficiency. Through in vitro cancer cell treatment testing, the proposed multifunctional NPs showed advanced photothermal and chemotherapeutic performance. Based on these enhanced anti-cancer properties, we expect that the proposed multifunctional NPs can be used as a drug-delivery system in cancer therapy.

A Magnetically Actuated Microscaffold Containing Mesenchymal Stem Cells for Articular Cartilage Repair.

This study proposes a magnetically actuated microscaffold with the capability of targeted mesenchymal stem cell (MSC) delivery for articular cartilage regeneration. The microscaffold, as a 3D porous microbead, is divided into body and surface portions according to its materials and fabrication methods. The microscaffold body, which consists of poly(lactic-co-glycolic acid) (PLGA), is formed through water-in-oil-in-water emulsion templating, and its surface is coated with amine functionalized magnetic nanoparticles (MNPs) via amino bond formation. The porous PLGA structure of the microscaffold can assist in cell adhesion and migration, and the MNPs on the microscaffold can make it possible to steer using an electromagnetic actuation system that provides external magnetic fields for the 3D locomotion of the microscaffold. As a fundamental test of the magnetic response of the microscaffold, it is characterized in terms of the magnetization curve, velocity, and 3D locomotion of a single microscaffold. In addition, its function with a cargo of MSCs for cartilage regeneration is demonstrated from the proliferation, viability, and chondrogenic differentiation of D1 mouse MSCs that are cultured on the microscaffold. For the feasibility tests for cartilage repair, 2D/3D targeting of multiple microscaffolds with the MSCs is performed to demonstrate targeted stem cell delivery using the microscaffolds and their swarm motion.

Nanohybrid magnetic liposome functionalized with hyaluronic acid for enhanced cellular uptake and near-infrared-triggered drug release.

The aim of this work is to prepare and evaluate a novel lipid-polymer hybrid liposomal nanoplatform (hyaluronic acid-magnetic nanoparticle-liposomes, HA-MNP-LPs) as a vehicle for targeted delivery and triggered release of an anticancer drug (docetaxel, DTX) in human breast cancer cells. We first synthesize an amphiphilic hyaluronic acid hexadecylamine polymer (HA-C16) to enhance the targeting ability of the hybrid liposome. Next, HA-MNP-LPs are constructed to achieve an average size of 189.93±2.74nm in diameter. In addition, citric acid-coated magnetic nanoparticles (MNPs) are prepared and embedded in the aqueous cores while DTX is encapsulated in the hydrophobic bilayers of the liposomes. Experiments with coumarin 6 loaded hybrid liposomes (C6/HA-MNP-LPs) show that the hybrid liposomes have superior cellular uptake in comparison with the conventional non-targeting liposomes (C6/MNP-LPs), and the result is further confirmed by Prussian blue staining. Under near-infrared laser irradiation (NIR, 808nm), the HA-MNP-LPs aqueous solution can reach 46.7°C in 10min, and the hybrid liposomes released over 20% more drug than the non-irradiated liposomes. Using a combination of photothermal irradiation and chemotherapy, the DTX-loaded hybrid liposomes (DTX/HA-MNP-LPs) significantly enhance therapeutic efficacy, with the IC50 value of 0.69±0.10µg/mL, which is much lower than the values for DTX monotherapy. Consequently, the prepared hybrid nanoplatform may offer a promising drug delivery vehicle with selective targeting and enhanced drug release in treating CD44-overexpressing cancers.