Purification of Therapeutic Antibodies Using the Ca2+-Dependent Phase-Transition Properties of Calsequestrin.

Affinity chromatography utilizing specific interactions between therapeutic proteins and bead-immobilized capturing agents is a standard method for protein purification, but its scalability is limited by long purification times, activity loss by the capturing molecules and/or purified protein, and high costs. Here, we report a platform for purifying therapeutic antibodies via affinity precipitation using the endogenous calcium ion-binding protein, calsequestrin (CSQ), which undergoes a calcium ion-dependent phase transition. In this method, ZZ-CSQ fusion proteins with CSQ and an affinity protein (Z domain of protein A) capture antibodies and undergo multimerization and subsequent aggregation in response to calcium ions, enabling the antibody to be collected by affinity precipitation. After robustly validating and optimizing the performance of the platform, the ZZ-CSQ platform can rapidly purify therapeutic antibodies from industrial harvest feedstock with high purity (>97%) and recovery yield (95% ± 3%). In addition, the ZZ-CSQ platform outperforms protein A-based affinity chromatography (PAC) in removing impurities, yielding ∼20-fold less DNA and ∼4.8-fold less host cell protein (HCP) contamination. Taken together, this platform is rapid, recyclable, scalable, and cost-effective, and it shows antibody-purification performance superior or comparable to that of the standard affinity chromatography method.

All-in-one nanosponge with pluronic shell for synergistic anticancer therapy through effectively overcoming multidrug resistance in cancer.

Overexpression of P-glycoprotein (P-gp) on cancer cells is a major hurdle to effectively treat tumors with multidrug resistance (MDR). The current study aimed to explore anticancer drug and P-gp inhibitor delivery as a promising strategy to efficiently treat colorectal cancer with MDR. To this end, a multidrug-loaded all-in-one nanosponge (ANS) was developed to simultaneously deliver doxorubicin (DOX), paclitaxel (PTX), and the P-gp inhibitor tetrandrine (TET), referred to as DOX/PTX/TET@ANS, without chemical conjugation. ANS with high loading content and efficiency facilitated a pH-dependent and controlled release with different profiles. Compared to free drugs and DOX/PTX@ANS, DOX/PTX/TET@ANS exhibited more effective anticancer effects on P-gp-overexpressing colorectal cancer cells and solid tumor mouse xenografts, without major toxicity. Notably, ANS composed of pluronic shell induced in vitro P-gp inhibition compared to TET, implying a synergistic anticancer effect. These findings suggest that ANS can encapsulate multiple drugs to efficiently deliver chemotherapy, particularly in MDR tumors.

Nanoparticle Encapsulation of the Hexane Fraction of Cyperus Rotundus Extract for Enhanced Antioxidant and Anti-Inflammatory Activities in vitro.

Aim: Cyperus rotundus L. (CR) is traditionally used in medicine for its anti-inflammatory properties. In particular, α-cyperone, which is isolated from the essential oil and found primarily in the n-hexane fraction of the ethanolic extract, is known to inhibit NO production in LPS-stimulated RAW 264.7 cells. However, high concentrations of α-cyperone are required for sufficient anti-inflammatory activity. Even, essential oil obtained from C. rotundus has the disadvantage of low solubility and stability in aqueous environment, which makes it difficult to be applied in various fields and easily loses its activity. Therefore, in this study, we aimed to increase the extraction yield of C. rotundus by microbubble extraction and prepare nanoparticles (NPs) that can preserve its activity in a stable and bioavailable manner by utilizing nanoprecipitation. Methods: C. rotundus rhizomes were extracted in 50% ethanol using microbubbles and then fractionated with n-hexane to obtain α-cyperone-rich C. rotundus n-hexane fraction (CRHF). The biodegradable plant extract, α-cyperone, was prepared as green nanoparticles (CR@NPs) by nanoprecipitation technique under mild reaction conditions. The physicochemical properties of CR@NPs, including size, polydispersity index, and surface charge, were determined using dynamic light scattering. The extraction yield and encapsulation efficiency of α-cyperone were quantified by high-performance liquid chromatography. Antioxidant and anti-inflammatory activities were evaluated by DPPH assay and in vitro ROS and NO assays, and biocompatibility was assessed by MTT assay. Results: C. rotundus loaded nanoparticles demonstrated overcoming the limitation of α-cyperone solubility and stability in CRHF and also the antioxidant, anti-inflammatory properties as evidenced by in vitro assays in cellular models. Conclusion: The versatility of green chemistry, such as α-cyperone, enables the production of nanoparticles with promising biomedical applications such as cosmetics, pharmaceuticals, and food products.

Tumor cell loaded thermosensitive hydrogel for photodynamic therapy associated tumor antigens release.

BACKGROUND: Immunotherapy is a powerful strategy for treating cancer and can be used to inhibit the post-surgical relapse of tumors. METHODS: To achieve this, a Cell@hydrogel was developed as a template using a mixture of CT26 tumor cells and Pluronic® F-127/gelatin. RESULTS: The proposed mixture has a solution-to-gelation functionality and vice versa. The morphology of the Cell@hydrogel was characterized by scanning electron microscopy and confocal microscopy. For photodynamic immunotherapy, the Cell@hydrogel was functionalized with Cy7 (Cy7-Cell@hydrogel) to quantify reactive oxygen species in CT26 tumor cells. Gel electrophoresis and membrane integrity tests were performed to determine the efficiency of the Cy7-Cell@hydrogel following photodynamic therapy. CONCLUSIONS: This protocol provides an alternative approach that mechanistically inhibits the post-surgical relapse of solid tumors based on immunotherapy.

A novel transdermal drug delivery system: drug-loaded ROS-responsive ferrocene fibers for effective photoprotective and wound healing activity.

The present study proposes an innovative transdermal drug delivery system using ferrocene-incorporated fibers to enhance the bioavailability and therapeutic efficacy of ascorbyl tetraisopalmitate. Using electrospinning technology, the authors created ferrocene polymer fibers capable of highly efficient drug encapsulation and controlled release in response to reactive oxygen species commonly found in wound sites. The approach improves upon previous methods significantly by offering higher drug loading capacities and sustained release, directly targeting diseased cells. The results confirm the potential of ferrocene fibers for localized drug delivery, potentially reducing side effects and increasing patient convenience. The method could facilitate the application of bioactive compounds in medical textiles and targeted therapy.

Phytochemical-Based Nanoantioxidants Stabilized with Polyvinylpyrrolidone for Enhanced Antibacterial, Antioxidant, and Anti-Inflammatory Activities.

Despite the inhibitory effect of phytoncide (Pht) on food-borne pathogenic bacterial growth, the hydrophobic nature and susceptibility to biodegradation under physiological conditions limits its applications. Here, we developed Pht-loaded polyvinylpyrrolidone (PVP) micelles (Pht@PVP MC) via micelle packing. Pht was solubilized using different types of PVP as micellar vehicles. The as-prepared Pht@PVP MCs were characterized using dynamic light scattering and transmission electron microscopy. The sizes of the Pht@PVP MCs were controlled from 301 ± 51 to 80 ± 3 nm by adjusting the PVP content. The polydispersity index of Pht@PVP MC was between 0.21 ± 0.03 and 0.16 ± 0.04, indicating homogeneous size. A colony-counting method was employed to evaluate the improvement in antibacterial activity after Pht encapsulation in PVP micelles. The reactive oxygen species (ROS)-scavenging activity and anti-inflammatory efficacy of Pht@PVP MC were analyzed in a concentration range of 10-100 µg/mL by evaluating in vitro ROS and nitric oxide levels using DCFDA and Griess reagents. PVP with both hydrophobic and hydrophilic moieties improved the aqueous solubility of Pht and stabilized it via steric hindrance. Higher-molecular-weight PVP at higher concentrations resulted in a smaller hydrodynamic diameter of Pht@PVP MC with uniform size distribution. The spherical Pht@PVP MC maintained its size and polydispersity index in a biological buffer for 2 weeks. Pht@PVP MC exhibited enhanced antibacterial activity compared to bare Pht. The growth of Staphylococcus aureus was effectively inhibited by Pht@PVP MC treatment. Furthermore, biocompatible Pht@PVP MC exhibited dose-dependent antioxidant and anti-inflammatory activities in vitro. Overall, Pht@PVP MC is an effective alternative to synthetic antibacterial, antioxidant, and anti-inflammatory chemicals.

High-density immobilization of antibodies onto nanobead-coated cyclic olefin copolymer plastic surfaces for application as a sensitive immunoassay chip.

Our research efforts have been devoted to development of nanobead multilayer-based sensitive immunoassays on cyclic olefin copolymer (COC) plastic surfaces. To facilitate nanobead attachment and impart antibiofouling properties to a COC substrate, we used an amphiphilic copolymer comprising benzyl, polyethylene glycol, and reactive ester moieties to coat the hydrophobic COC surface in an aqueous environment. Subsequently, NH2-modified polystyrene nanobeads were reacted with the polymer-coated COC surface and further assembled into multilayers that increased the overall surface area available for attaching capture antibodies. After treatment of the nanobead multilayers with an amine-reactive homobifunctional crosslinker, a model capture antibody (anti-rabbit IgG) was covalently immobilized onto the activated surface of nanobeads. Finally, a sandwich immunoassay was carried out using rabbit IgG as a target analyte and rhodamine-labeled anti-rabbit IgG as a probe. Compared with a nanobead-free, polymer-coated COC surface, the nanobead multilayer-based immunoassay exhibited ~4-fold higher fluorescence intensity. In addition, our nanobead-based assay system exhibited a wide dynamic range of detection (0.1 to 1,000 ng/mL) and high specificity for rabbit IgG. Furthermore, much better detection sensitivity for rabbit IgG was attained in the nanobead multilayer-based immunoassay than with a conventional ELISA system (0.1 ng/mL versus 10 ng/mL), indicating the potential value of the proposed immunoassay system in plastic-based portable biochip applications.

Pluronic F-68 and F-127 Based Nanomedicines for Advancing Combination Cancer Therapy.

Pluronics are amphiphilic triblock copolymers composed of two hydrophilic poly (ethylene oxide) (PEO) chains linked via a central hydrophobic polypropylene oxide (PPO). Owing to their low molecular weight polymer and greater number of PEO segments, Pluronics induce micelle formation and gelation at critical micelle concentrations and temperatures. Pluronics F-68 and F-127 are the only United States (U.S.) FDA-approved classes of Pluronics and have been extensively used as materials for living bodies. Owing to the fascinating characteristics of Pluronics, many studies have suggested their role in biomedical applications, such as drug delivery systems, tissue regeneration scaffolders, and biosurfactants. As a result, various studies have been performed using Pluronics as a tool in nanomedicine and targeted delivery systems. This review sought to describe the delivery of therapeutic cargos using Pluronic F-68 and F-127-based cancer nanomedicines and their composites for combination therapy.

Facile Fabrication of α-Bisabolol Nanoparticles with Improved Antioxidant and Antibacterial Effects.

Bioactive compounds are widely used in the bio-industry because of their antioxidant and antibacterial activities. Because of excessive oxidative stress, which causes various diseases in humans, and because preservatives used in bioproducts cause allergies and contact dermatitis, it is important to use natural bioactive compounds in bioproducts to minimize oxidative stress. α-bisabolol (ABS) is a natural compound with both antioxidant and antibacterial properties. However, its water-insolubility makes its utilization in bioproducts difficult. In this study, ABS-loaded polyglyceryl-4 caprate nanoparticles (ABS@NPs) with improved aqueous stability and ABS loading were fabricated using an encapsulation method. The long-term stability of the ABS@NPs was analyzed with dynamic light scattering and methylene blue-staining to determine the optimized ABS concentration in ABS@NPs (10 wt%). The ABS@NPs exhibited excellent antioxidant activity, according to the 2,2-diphenyl-1-picrylhydrazyl assay and in vitro reactive oxygen species generation in NIH-3T3 fibroblast cells, and an outstanding antibacterial effect, as determined using the Staphylococcus aureus colony-counting method. Furthermore, we evaluated the biocompatibility of the ABS@NPs in vitro. This study suggests that ABS@NPs with improved antioxidant and antibacterial properties can be used to treat diseases related to various oxidative stresses and can be applied in many fields, such as pharmaceuticals, cosmetics, and foods.

Highly Water-Dispersed and Stable Deinoxanthin Nanocapsule for Effective Antioxidant and Anti-Inflammatory Activity.

Introduction: Deinoxanthin (DX), a carotenoid, has excellent antioxidant and anti-inflammatory properties. However, owing to its lipophilicity, it is unfavorably dispersed in water and has low stability, limiting its application in cosmetics, food, and pharmaceuticals. Therefore, it is necessary to study nanoparticles to increase the loading capacity and stability of DX. Methods: In this study, DX-loaded nanocapsules (DX@NCs) were prepared by nanoprecipitation by loading DX into nanocapsules. The size, polydispersity index, surface charge, and morphology of DX@NCs were confirmed through dynamic light scattering and transmission electron microscopy. The loading content and loading efficiency of DX in DX@NCs were analyzed using high-performance liquid chromatography. The antioxidant activity of DX@NCs was evaluated by DPPH assay and in vitro ROS. The biocompatibility of DX@NCs was evaluated using an in vitro MTT assay. In vitro NO analysis was performed to determine the effective anti-inflammatory efficacy of DX@NCs. Results: DX@NCs exhibited increased stability and antioxidant efficacy owing to the improved water solubility of DX. The in situ and in vitro antioxidant activity of DX@NCs was higher than that of unloaded DX. In addition, it showed a strong anti-inflammatory effect by regulating the NO level in an in vitro cell model. Conclusion: This study presents a nanocarrier to improve the water-soluble dispersion and stability of DX. These results demonstrate that DX@NC is a carrier with excellent stability and has a high potential for use in cosmetic and pharmaceutical applications owing to its antioxidant and anti-inflammatory effects.

ROS-responsive PEGylated ferrocene polymer nanoparticles with improved stability for tumor-selective chemotherapy and imaging.

Ferrocene-based nanoparticles have garnered interest as reactive oxygen species (ROS)-responsive nanocarriers of anticancer drugs and imaging agents. However, their biomedical applications remain limited due to their poor physiological stability. PEGylation of nanocarriers improves their stability and biocompatibility. In this study, we aimed to develop novel PEG-ferrocene nanoparticles (PFNPs) with enhanced stability and ROS responsiveness for the delivery of paclitaxel (PTX) and imaging agents. PEGylation improved the stability of ferrocene nanoparticles, inhibiting their ROS-responsive destruction. Several PEG-ferrocene polymers containing different molar ratios of methacrylic acid and poly (ethylene glycol) methyl ether methacrylate was designed for optimization. ROS-responsive polymers with optimal monomer ratios were self-assembled into PFNPs with enhanced stability. The PFNPs distended, effectively releasing encapsulated PTX and imaging agents within 8 h in the presence of ROS. Furthermore, they remained stable, with no changes in their hydrodynamic diameters or polydispersity indexes after storage in an aqueous solution and biological buffer. The accumulation of PFNPs in a tumor model in vivo was 15-fold higher than a free dye. PTX-loaded PFNPs showed a substantial tumor-suppression effect, reducing tumor size to approximately 18% of that in the corresponding control group. These findings suggest a promising application of ROS-responsive PFNPs in tumor treatment as biocompatible nanocarriers of anticancer drugs and imaging agents.

Mesoporous Silica Nanoparticles as a Gene Delivery Platform for Cancer Therapy.

Cancer remains a major global health challenge. Traditional chemotherapy often results in side effects and drug resistance, necessitating the development of alternative treatment strategies such as gene therapy. Mesoporous silica nanoparticles (MSNs) offer many advantages as a gene delivery carrier, including high loading capacity, controlled drug release, and easy surface functionalization. MSNs are biodegradable and biocompatible, making them promising candidates for drug delivery applications. Recent studies demonstrating the use of MSNs for the delivery of therapeutic nucleic acids to cancer cells have been reviewed, along with their potential as a tool for cancer therapy. The major challenges and future interventions of MSNs as gene delivery carriers for cancer therapy are discussed.

An electrochemically reduced graphene oxide-based electrochemical immunosensing platform for ultrasensitive antigen detection.

We present an electrochemically reduced graphene oxide (ERGO)-based electrochemical immunosensing platform for the ultrasensitive detection of an antigen by the sandwich enzyme-linked immunosorbent assay (ELISA) protocol. Graphene oxide (GO) sheets were initially deposited on the amine-terminated benzenediazonium-modified indiun tin oxide (ITO) surfaces through both electrostatic and π-π interactions between the modified surfaces and GO. This deposition was followed by the electrochemical reduction of graphene oxide (GO) for preparing ERGO-modified ITO surfaces. These surfaces were then coated with an N-acryloxysuccinimide-activated amphiphilic polymer, poly(BMA-r-PEGMA-r-NAS), through π-π stacking interactions between the benzene ring tethered to the polymer and ERGO. After covalent immobilization of a primary antibody on the polymer-modified surfaces, sandwich ELISA was carried out for the detection of an antigen by use of a horseradish peroxidase (HRP)-labeled secondary antibody. Under the optimized experimental conditions, the developed electrochemical immunosensor exhibited a linear response over a wide range of antigen concentrations with a very low limit of detection (ca. 100 fg/mL, which corresponds to ca. 700 aM). The high sensitivity of the electrochemical immunosensor may be attributed not only to the enhanced electrocatalytic activity owing to ERGO but also to the minimized background current owing to the reduced nonspecific binding of proteins.

Facile immobilization of biomolecules onto various surfaces using epoxide-containing antibiofouling polymers.

The surface modifications of plastic or glass substrate and the subsequent immobilization of biomolecules onto the surfaces has been a central feature of the fabrication of biochips. To this end, we designed and synthesized new epoxide-containing random copolymers that form stable polymer adlayers on plastic or glass surface and subsequently react with amine or sulfhydryl functional groups of biomolecules under aqueous conditions. Epoxide-containing random copolymers were synthesized by radical polymerization of three functional monomers: a monomer acting as an anchor to the surfaces, a PEG group for preventing nonspecific protein adsorption, and an epoxide group for conjugating to biomolecules. Polymer coating layers were facilely formed on cyclic olefin copolymer (COC) or glass substrate by simply dipping each substrate into a solution of each copolymer. The polymer-coated surfaces characterized by a contact angle analyzer and X-ray photoelectron spectroscopy (XPS) showed very low levels of nonspecific immunoglobulin G (IgG) adsorption compared to the uncoated bare surface (control). Using a microcontact printing (µCP) method, antibodies as representative biomolecules could be selectively attached onto the copolymers-coated glass or COC surface with high signal-to-noise ratios.

Size-Controllable Prussian Blue Nanoparticles Using Pluronic Series for Improved Antioxidant Activity and Anti-Inflammatory Efficacy.

Prussian blue (PB) is a metal cluster nanoparticle (NP) of cyanide-bridged iron(II)-iron(III) and exhibits a characteristic blue color. Its peroxidase-, catalase-, and superoxide-dismutase-like activities effectively remove excess reactive oxygen species that induce inflammation and tumorigenesis. However, the dispersion of PB NPs is not sufficiently stable for their application in the biomedical field. In this study, we developed Pluronic-stabilized Prussian blue nanoparticles (PB/Plu NPs) using a series of Pluronic triblock copolymers as a template material for PB NPs. Considering the hydrophilic-lipophilic balance (HLB) values of the Pluronic series, including F68, F127, L35, P123, and L81, the diameters of the PB/Plu NPs decreased from 294 to 112 nm with decreasing HLB values. The smallest PB NP stabilized with Pluronic P123 (PB/PP123 NP) showed the strongest antioxidant and anti-inflammatory activities and wound-healing efficacy because of its large surface area. These results indicated that the spatial distribution of PB NPs in the micelles of Pluronic greatly improved the stability and reactive oxygen species scavenging activity of these NPs. Therefore, PB/Plu NPs using U.S.-FDA-approved Pluronic polymers show potential as biocompatible materials for various biomedical applications, including the treatment of inflammatory diseases in the clinic.

Reactive oxygen species scavenging nanofibers with chitosan-stabilized Prussian blue nanoparticles for enhanced wound healing efficacy.

Chronic inflammatory wounds pose therapeutic challenges in the biomedical field. Polymeric nanofibrous matrices provide extracellular-matrix-like structures to facilitate wound healing; however, wound infection and the subsequent accumulation of reactive oxygen species (ROS) delay healing. Therefore, we herein developed electrospun nanofibers (NFs), composed of chitosan-stabilized Prussian blue (PBChi) nanoparticles (NPs) and poly(vinyl alcohol) (PVA), with ROS scavenging activity to impart antioxidant and wound healing properties. The PBChi NPs were prepared using chitosan with different molecular weights, and their weight ratio with respect to PVA was optimized to yield PBChi-NP-coated PVA NFs with well-defined NF structures. In situ and in vitro antioxidant activity assays showed that the PBChi/PVA NFs could effectively remove ROS. Particularly, PBChi/PVA NFs with a lower chitosan molecular weight exhibited greater antioxidant activity. The hydroxyl radical scavenging activity of PBChi10k/PVA NFs was 60.4 %, approximately two-fold higher than that of PBChi100k/PVA NFs. Further, at the concentration of 10 µg/mL, they could significantly lower the in vitro ROS level by up to 50.7 %. The NFs caused no significant reduction in cell viability, owing to the excellent biocompatibility of PVA with PBChi NPs. Treatment using PBChi/PVA NFs led to faster cell proliferation in in vitro scratch wounds, reducing their size from 202 to 162 µm. The PBChi/PVA NFs possess notable antioxidant and cell proliferation properties as ROS-scavenging wound dressings.

Facile Solvent-Free Preparation of Antioxidant Idebenone-Loaded Nanoparticles for Efficient Wound Healing.

The excessive production of reactive oxygen species (ROS) causes harmful effects, including biomolecular damage and inflammation. ROS due to ultraviolet rays, blue light, and fine dust harm the skin, causing urban-related aging. Therefore, a strong antioxidant that relieves oxidative stress in the skin and removes ROS is required. Idebenone (IB) is a powerful antioxidant but is poorly soluble and thus has low solubility in water, resulting in low bioavailability. In this study, IB-loaded nanoparticles (IB@NPs) were synthesized by loading IB without an organic solvent into nanoparticles that can provide high loading efficiency and stability for solubilization. Indeed, the synthesized IB@NPs exhibited long-term stability through dynamic light scattering, methylene blue staining, and redispersion assays, and IB@NPs prepared with a 5 wt% IB loading content were found to be optimal. The antioxidant activity of IB@NPs evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was significantly higher than that of unloaded IB. In addition, IB@NPs showed excellent biocompatibility, inhibited oxidative damage to mouse NIH-3T3 fibroblasts, and reduced intracellular ROS generation according to an in vitro DPPH antioxidant assay. Most notably, IB@NPs significantly promoted wound healing in vitro, as demonstrated by scratch assays. Therefore, as carriers with excellent stability, IB@NPs have potential cosmetic and pharmaceutical applications.

Novel carboxylated ferrocene polymer nanocapsule with high reactive oxygen species sensitivity and on-demand drug release for effective cancer therapy.

Multidrug resistance (MDR) is a major clinical issue leading to substantial reductions in the intracellular levels of anticancer drugs. To overcome MDR, stimulus-responsive polymeric nanotherapeutics that facilitate drug release and cellular uptake at target sites have emerged as promising tools for safe and effective cancer treatment. Among these nanotherapeutics, reactive oxygen species (ROS)-responsive nanocapsules are ideal carriers, as abnormally increased ROS levels can drive controlled drug release at target sites. In this study, we developed novel, high ROS-responsive carboxylated ferrocene nanocapsules (CFNCs) using solvents of different polarities for effective multidrug-resistant cancer therapy. The CFNCs were prepared via the self-assembly of an amphiphilic carboxylated ferrocene polymer composed of a hydrophilic COOH segment and a hydrophobic ferrocenylmethyl methacrylate segment possessing a ROS-responsive group. The size and ROS sensitivity of self-assembled CFNCs could be controlled by using solvents of different polarities during the simple nanoprecipitation process. The CFNCs showed a high loading content (approximately 30 wt%) and on-demand release of paclitaxel under both normal and tumor-mimicking conditions, and exhibited synergistic anticancer effects in multidrug-resistant colorectal cancer cells (HCT-15). Our findings suggest that CFNCs can be applied as carriers for effective cancer therapy.

α-Tocopherol-loaded reactive oxygen species-scavenging ferrocene nanocapsules with high antioxidant efficacy for wound healing.

The elevated production of reactive oxygen species (ROS) in wounded sites triggers a series of harmful effects, including cellular senescence, fibrotic scar formation, and inflammation. Therefore, alleviating oxidative stress in the microenvironment of wounded sites might promote regenerative wound healing. Generally, ROS-scavenging nanocapsules are effective for treating wounds owing to their anti-oxidative stress activity and targeted effects. In this study, a highly versatile ferrocene functional polymer was synthesized by one-pot radical polymerization, for formulating self-assembled ferrocene nanocapsules (FNCs), which could function as smart carriers of an antioxidant, α-tocopherol (TP), with high stability and loading efficiency. The FNCs showed ROS-sensitive properties, as demonstrated using dynamic light scattering, transmission electron microscopy, and the controlled release of a model drug in an ROS microenvironment. The antioxidant activity of TP-loaded FNCs, analyzed using 2,2-diphenyl-1-picrylhydrazyl assay, was significantly higher than that of unloaded TP. Furthermore, TP-loaded FNCs repressed oxidative damage to mouse NIH 3T3 fibroblasts and reduced intracellular ROS production according to an in vitro antioxidant assay. Most importantly, TP-loaded FNCs showed good biocompatibility and greatly facilitated the healing of infected wounds, as demonstrated using a scratch assay. Therefore, TP-loaded FNCs have potential as an ROS-mediated drug delivery system to treat various oxidative stress-associated diseases.

High Solubilization and Controlled Release of Paclitaxel Using Thermosponge Nanoparticles for Effective Cancer Therapy.

Cancer, which is a leading cause of death, contributes significantly to reducing life expectancy worldwide. Even though paclitaxel (PTX) is known as one of the main anticancer drugs, it has several limitations, including low solubility in aqueous solutions, a limited dosage range, an insufficient release amount, and patient resistance. To overcome these limitations, we suggest the development of PTX-loaded thermosponge nanoparticles (PTX@TNP), which result in improved anticancer effects, via a simple nanoprecipitation method, which allows the preparation of PTX@TNPs with hydrophobic interactions without any chemical conjugation. Further, to improve the drug content and yield of the prepared complex, the co-organic solvent ratio was optimized. Thus, it was observed that the drug release rate increased as the drug capacity of PTX@TNPs increased. Furthermore, increasing PTX loading led to considerable anticancer activity against multidrug resistance (MDR)-related colorectal cancer cells (HCT 15), implying a synergistic anticancer effect. These results suggest that the solubilization of high drug amounts and the controlled release of poorly water-soluble PTX using TNPs could significantly improve its anticancer therapy, particularly in the treatment of MDR-p-glycoprotein-overexpressing cancers.