Ambient Humidity-Induced Phase Separation for Fiber Morphology Engineering toward Piezoelectric Self-Powered Sensing.

Electrospun polymeric piezoelectric fibers have a considerable potential for shape-adaptive mechanical energy harvesting and self-powered sensing in biomedical, wearable, and industrial applications. However, their unsatisfactory piezoelectric performance remains an issue to be overcome. While strategies for increasing the crystallinity of electroactive ß phases have thus far been the major focus in realizing enhanced piezoelectric performance, tailoring the fiber morphology can also be a promising alternative. Herein, a design strategy that combines the nonsolvent-induced phase separation of a polymer/solvent/water ternary system and electrospinning for fabricating piezoelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE) fibers with surface porosity under ambient humidity is presented. Notably, electrospun P(VDF-TrFE) fibers with higher surface porosity outperform their smooth-surfaced counterparts with a higher ß phase content in terms of output voltage and power generation. Theoretical and numerical studies also underpin the contribution of the structural porosity to the harvesting performance, which is attributable to local stress concentration and reduced dielectric constant due to the air in the pores. This porous fiber design can broaden the application prospects of shape-adaptive energy harvesting and self-powered sensing based on piezoelectric polymer fibers with enhanced voltage and power performance, as successfully demonstrated in this work by developing a communication system based on self-powered motion sensing.

Anticariogenic Potential of Korean Native Plant Extracts against Streptococcus mutans.

Numerous chemically synthesized compounds are widely used in oral hygiene products. However, due to their potential risk, there is a need to improve the safety and quality of dental care by seeking alternative control agents such as those naturally found in plant materials. Here we assessed antibacterial potentials of extracts from 100 species of Korean native plants against Streptococcus mutans on cariogenesis. Among those, extracts from five plants (Arctii Fructus, Caryopteris incana, Aralia continentalis, Symplocarpus renifolius, and Lamium amplexicaule) showed a growth inhibition of S. mutans. The five extracts were further individually evaluated for their minimal inhibitory concentration and minimal bactericidal concentration. Interestingly, a synergistic antibacterial activity was observed with the combination of sodium fluoride and the plant extracts. To determine the anti-biofilm activity of plant extracts, S. mutans was treated with increasing concentrations of the extracts in the range from 1250 to 3750 µg/mL. When S. mutans was grown in the defined biofilm medium containing the individual extracts of 47 species, the biofilm amount markedly decreased compared to that of a negative control. Notably, the extract of S. renifolius significantly downregulated the gtf and spaP genes for synthesis of glucan and adhesive proteins in S. mutans, and L. amplexicaule decreased the expression of gtfD gene. Therefore, these results demonstrate that the five plant extracts modulate survival and pathogenesis of S. mutans by growth inhibition and downregulation of the gene(s) implicated in biofilm formation.

Comparison of Clinical Outcomes and Computed Tomography Analysis for Tunnel Diameter After Arthroscopic Bankart Repair With the All-Suture Anchor and the Biodegradable Suture Anchor.

PURPOSE: To compare the clinical outcomes and radiological findings at the anchor site after arthroscopic Bankart repair with all-suture anchors and biodegradable suture anchors in patients with recurrent anterior shoulder dislocation. METHODS: The patients who underwent arthroscopic Bankart repair were divided into 2 groups depending on the type of the suture anchor used in different periods. Power analysis was designed based on the postoperative Rowe score. Clinical outcomes, including the Rowe score, American Shoulder and Elbow Surgeons score, subjective instability, and redislocation rates were evaluated. In all patients enrolled, the tunnel diameter of the anchor was assessed with computed tomography arthrogram at 1 year postoperatively. The Institutional Review Board of Ewha Womans University approved this study (no. EUMC 2017-05-058). RESULTS: A total of 67 patients were enrolled: 33 underwent surgery with a 1.3-mm (single-loaded) or 1.8-mm (double-loaded) all-suture anchor (group A), and 34 underwent surgery with a 3.0-mm biodegradable anchor (10.8 mm in length, 30% 1,2,3-trichloropropane/70% poly-lactide-co-glycolic acid) (group B). There were no significant differences in clinical outcomes between groups A and B in the American Shoulder and Elbow Surgeons score (preoperatively, 51.2 ± 13.7 vs 47.7 ± 12.2; 2 years postoperatively, 88.5 ± 12.3 vs 89.7 ± 10.9; P = .667) and Rowe score (preoperatively, 41.4 ± 10.5 vs 41.3 ± 9.4; 2 years postoperatively, 87.9 ± 14.9 vs 88.5 ± 14.6; P = .857). Postoperative redislocation (6.1% vs 5.9%, P = .682) and subjective instability rate (12.2% vs 17.7%, P = .386) of both groups showed no significant difference. Average tunnel diameter increment was significantly greater with the 1.8-mm all-suture anchor (2.8 ± 0.9 mm) than the 1.3-mm all-suture anchor (1.2 ± 0.8 mm) and 3.0-mm biodegradable anchor (0.8 ± 1.2 mm) (P < .001). CONCLUSIONS: Arthroscopic Bankart repair with the all-suture anchor showed comparable clinical outcomes and postoperative stability as the conventional biodegradable suture anchor at 2 years after surgery. Tunnel diameter increment of the all-suture anchor was significantly greater than that of the biodegradable suture anchor at the 1-year computed tomography analysis. Although tunnel diameter increment was greater with the all-suture anchor, it did not influence the clinical outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PEGylated anticancer-carbon nanotubes complex targeting mitochondria of lung cancer cells.

Although activating apoptosis in cancer cells by targeting the mitochondria is an effective strategy for cancer therapy, insufficient targeting of the mitochondria in cancer cells restricts the availability in clinical treatment. Here, we report on a polyethylene glycol-coated carbon nanotube (CNT)-ABT737 nanodrug that improves the mitochondrial targeting of lung cancer cells. The polyethylene glycol-coated CNT-ABT737 nanodrug internalized into the early endosomes via macropinocytosis and clathrin-mediated endocytosis in advance of early endosomal escape and delivered into the mitochondria. Cytosol release of the nanodrug led to apoptosis of lung cancer cells by abruption of the mitochondrial membrane potential, inducing Bcl-2-mediated apoptosis and generating intracellular reactive oxygen species. As such, this study provides an effective strategy for increasing the anti-lung cancer efficacy by increasing mitochondria accumulation rate of cytosol released anticancer nanodrugs.

Self-Powered Electrical Bandage Based on Body-Coupled Energy Harvesting.

Self-powered electrical bandages (SEBs), integrated with wearable energy harvesters, can provide an effective and autonomous electrical stimulation (ES) solution for rapid and scarless wound healing. A continuously operating, wireless, and applicable-to-comprehensive-wound ES device is essential for the quick restoration of wounds and convenience. This work illustrates a SEB powered by body-coupled energy harvesting. The SEB continuously treats the wound with 60-Hz sinusoidal electrical potential gained from the coupling of the human body and ambient electrical waves. It is demonstrated that enough level of electrical potential can be applied to the wound, further enhanced by strong capacitive coupling arising from the use of high-permittivity poly(vinylidene fluoride-trifluoroethylene):CaCu3Ti4O12 (P(VDF-TrFE):CCTO) nanocomposite. The potential clinical efficacy of the SEB is illustrated by preclinical analysis of human fibroblasts and mouse wound model, thus confirming the successful expedition of wound recovery. This work suggests a new class of wearable devices to provide ES events and its potential for extension to other conventional wound care materials and device technology.

Striped, ellipsoidal particles by controlled assembly of diblock copolymers.

Control of interfacial interactions leads to a dramatic change in shape and morphology for particles based on poly(styrene-b-2-vinylpyridine) diblock copolymers. Key to these changes is the addition of Au-based surfactant nanoparticles (SNPs) which are adsorbed at the interface between block copolymer-containing emulsion droplets and the surrounding amphiphilic surfactant to afford asymmetric, ellipsoid particles. The mechanism of formation for these novel nanostructures was investigated by systematically varying the volume fraction of SNPs, with the results showing the critical nature that the segregation of SNPs to specific interfaces plays in controlling structure. A theoretical description of the system allows the size distribution and aspect ratio of the asymmetric block copolymer colloidal particles to be correlated with the experimental results.

p-Type polymer-hybridized high-performance piezoelectric nanogenerators.

Enhancing the output power of a nanogenerator is essential in applications as a sustainable power source for wireless sensors and microelectronics. We report here a novel approach that greatly enhances piezoelectric power generation by introducing a p-type polymer layer on a piezoelectric semiconducting thin film. Holes at the film surface greatly reduce the piezoelectric potential screening effect caused by free electrons in a piezoelectric semiconducting material. Furthermore, additional carriers from a conducting polymer and a shift in the Fermi level help in increasing the power output. Poly(3-hexylthiophene) (P3HT) was used as a p-type polymer on piezoelectric semiconducting zinc oxide (ZnO) thin film, and phenyl-C(61)-butyric acid methyl ester (PCBM) was added to P3HT to improve carrier transport. The ZnO/P3HT:PCBM-assembled piezoelectric power generator demonstrated 18-fold enhancement in the output voltage and tripled the current, relative to a power generator with ZnO only at a strain of 0.068%. The overall output power density exceeded 0.88 W/cm(3), and the average power conversion efficiency was up to 18%. This high power generation enabled red, green, and blue light-emitting diodes to turn on after only tens of times bending the generator. This approach offers a breakthrough in realizing a high-performance flexible piezoelectric energy harvester for self-powered electronics.

An Ultrasound-Driven Bioadhesive Triboelectric Nanogenerator for Instant Wound Sealing and Electrically Accelerated Healing in Emergencies.

A bioadhesive triboelectric nanogenerator (BA-TENG), as a first-aid rescue for instant and robust wound sealing and ultrasound-driven accelerated wound healing, is designed. This BA-TENG is fabricated with biocompatible materials, and integrates a flexible TENG as the top layer and bioadhesive as the bottom layer, resulting in effective electricity supply and strong sutureless sealing capability on wet tissues. When driven by ultrasound, the BA-TENG can produce a stable voltage of 1.50 V and current of 24.20 µA underwater. The ex vivo porcine colon organ models show that the BA-TENG seals defects instantly (≈5 s) with high interfacial toughness (≈150 J m-2 ), while the rat bleeding liver incision model confirms that the BA-TENG performs rapid wound closure and hemostasis, reducing the blood loss by about 82%. When applied in living rats, the BA-TENG not only seals skin injuries immediately but also produces a strong electric field (E-field) of about 0.86 kV m-1 stimulated by ultrasound to accelerate skin wound healing significantly. The in vitro studies confirm that these effects are attributed to the E-field-accelerated cell migration and proliferation. In addition, these TENG adhesives can be applied to not only wound treatment, nerve stimulation and regeneration, and charging batteries in implanted devices.

A stamped PEDOT:PSS-silicon nanowire hybrid solar cell.

A novel stamped hybrid solar cell was proposed using the stamping transfer technique by stamping an active PEDOT:PSS thin layer onto the top of silicon nanowires (SiNWs). Compared to a bulk-type counterpart that fully embeds SiNWs inside PEDOT:PSS, an increase in the photovoltaic efficiency was observed by a factor of ∼4.6, along with improvements in both electrical and optical responses for the stamped hybrid cell. Such improvements for hybrid cells was due to the formation of well-connected and linearly aligned active PEDOT:PSS channels at the top ends of the nanowires after the stamping process. These stamped channels facilitated not only to improve the charge transport, light absorption, but also to decrease the free carriers as well as exciton recombination losses for stamped hybrid solar cells.

Transparent and Multi-Foldable Nanocellulose Paper Microsupercapacitors.

Despite the ever-increasing demand for transparent power sources in wireless optoelectronics, most of them have still relied on synthetic chemicals, thus limiting their versatile applications. Here, a class of transparent nanocellulose paper microsupercapacitors (TNP-MSCs) as a beyond-synthetic-material strategy is demonstrated. Onto semi-interpenetrating polymer network-structured, thiol-modified transparent nanocellulose paper, a thin layer of silver nanowire and a conducting polymer (chosen as a pseudocapacitive electrode material) are consecutively introduced through microscale-patterned masks (which are fabricated by electrohydrodynamic jet printing) to produce a transparent conductive electrode (TNP-TCE) with planar interdigitated structure. This TNP-TCE, in combination with solid-state gel electrolytes, enables on-demand (in-series/in-parallel) cell configurations in a single body of TNP-MSC. Driven by this structural uniqueness and scalable microfabrication, the TNP-MSC exhibits improvements in optical transparency (T = 85%), areal capacitance (0.24 mF cm-2 ), controllable voltage (7.2 V per cell), and mechanical flexibility (origami airplane), which exceed those of previously reported transparent MSCs based on synthetic chemicals.

Predictive Parameters of Febrile Neutropenia and Clinical Significance of G-CSF Receptor Signaling Pathway in the Development of Neutropenia during R-CHOP Chemotherapy with Prophylactic Pegfilgrastim in Patients with Diffuse Large B-Cell Lymphoma.

PURPOSE: Pegfilgrastim is widely used to prevent chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) in patients with diffuse large B-cell lymphoma (DLBCL). We investigated the predictive factors affecting CIN and FN incidence in patients with DLBCL receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy with pegfilgrastim and conducted experiments to find reason for the occurrence of CIN even when pegfilgrastim was used. MATERIALS AND METHODS: We reviewed the CIN and FN events of 200 patients with DLBCL. Based on these data, we investigate the association with predictive factor and the levels of granulocyte-colony stimulating factor (G-CSF) receptor signaling pathway markers (pSTAT3, pAKT, pERK1/2, pBAD, and CXCR4) in bone marrow (BM) samples isolated from patients with DLBCL. RESULTS: FN was significantly associated with stage III/IV (hazard ratio [HR], 12.74) and low serum albumin levels (HR, 3.87). Additionally, patients with FN had lower progression-free survival (PFS; 2-year PFS, 51.1 % vs. 74.0%) and overall survival (OS; 2-year OS, 58.2% vs. 85.0%) compared to those without FN. The occurrence of CIN was associated with overexpression of G-CSF receptor signaling pathway markers, and expression levels of these markers were upregulated in BM cells co-cultured with DLBCL cells. The rate of neutrophil apoptosis was also higher in neutrophils co-cultured with DLBCL cells and was further promoted by treatment with doxorubicin. CONCLUSION: Our findings suggest that high DLBCL burden may alter the BM environment and G-CSF receptor signaling pathway, even in chemotherapy-naïve state, which may increase CIN frequency during R-CHOP chemotherapy.

Soft-Tissue Grafting Solutions.

Many soft-tissue grafting solutions are available for reconstruction and restoration of volume and esthetics of keratinized attached mucosa at compromised periodontal and peri-implant interfaces. Presence of healthy soft tissues is crucial for functional and esthetic implant success as well as longevity of natural dentition. The options available each provide unique characteristics with different indications. This article is intended to provide an efficient and comprehensive overview of this topic, covering the essentials of periodontal anatomy and physiology, indications for soft-tissue grafting, and keys in recipient and donor-site preparation, and exploring the available procedural arsenal in soft-tissue grafting.

Biomolecular Piezoelectric Materials: From Amino Acids to Living Tissues.

Biomolecular piezoelectric materials are considered a strong candidate material for biomedical applications due to their robust piezoelectricity, biocompatibility, and low dielectric property. The electric field has been found to affect tissue development and regeneration, and the piezoelectric properties of biological materials in the human body are known to provide electric fields by pressure. Therefore, great attention has been paid to the understanding of piezoelectricity in biological tissues and its building blocks. The aim herein is to describe the principle of piezoelectricity in biological materials from the very basic building blocks (i.e., amino acids, peptides, proteins, etc.) to highly organized tissues (i.e., bones, skin, etc.). Research progress on the piezoelectricity within various biological materials is summarized, including amino acids, peptides, proteins, and tissues. The mechanisms and origin of piezoelectricity within various biological materials are also covered.

Reactive oxygen species-sensitive nanophotosensitizers of aminophenyl boronic acid pinacol ester conjugated chitosan-g-methoxy poly(ethylene glycol) copolymer for photodynamic treatment of cancer.

The aim of this study is to prepare reactive oxygen species (ROS)-sensitive nanophotosensitizers for targeted delivery of chlorin e6 (Ce6) and photodynamic tumor therapy. For this purpose, thiodipropionic acid (TDPA) was conjugated with phenyl boronic acid pinacol ester (PBAP) (TDPA-PBAP conjugates) and then the TDPA-PBAP conjugates were attached to the chitosan backbone of chitosan-g-methoxy poly(ethylene glycol) (ChitoPEG) copolymer (ChitoPEG-PBAP). Ce6-incorporated ChitoPEG-PBAP nanophotosensitizers have an ROS-sensitive manner in vitro. The size of ChitoPEG-PBAP nanoparticles increased or disintegrated in a responsive manner against H2O2 concentration. The Ce6 release rate from ChitoPEG-PBAP nanophotosensitizers also increased by adding H2O2. These results indicated that nanophotosensitizers have sensitivity against ROS and showed triggered Ce6 release behavior. ChitoPEG-PBAP nanophotosensitizers can be more efficiently internalized into cancer cells compared to Ce6 alone and then produce ROS in a more efficient manner. Furthermore, ChitoPEG-PBAP nanophotosensitizers suppressed the viability of cancer cells in vitro and tumor growth in vivo with higher efficacy compared to Ce6 alone. Furthermore, ChitoPEG-PBAP nanophotosensitizers were efficiently delivered to irradiated tumor tissues, indicating that ChitoPEG-PBAP nanophotosensitizers can be delivered to the tumor with ROS-sensitive manner. We suggest that a ChitoPEG-PBAP nanophotosensitizer is a promising candidate for photodynamic therapy of cancers.

Antiphase Boundaries as Faceted Metallic Wires in 2D Transition Metal Dichalcogenides.

Antiphase boundaries (APBs) in 2D transition metal dichalcogenides have attracted wide interest as 1D metallic wires embedded in a semiconducting matrix, which could be exploited in fully 2D-integrated circuits. Here, the anisotropic morphologies of APBs (i.e., linear and saw-toothed APBs) in the nanoscale are investigated. The experimental and computational results show that despite their anisotropic nanoscale morphologies, all APBs adopt a predominantly chalcogen-oriented dense structure to maintain the energetically most stable atomic configuration. Moreover, the effect of the nanoscale morphology of an APB on electron transport from two-probe field effect transistor measurements is investigated. A saw-toothed APB has a considerably lower electron mobility than a linear APB, indicating that kinks between facets are the main factors of scattering. The observations contribute to the systematical understanding of the faceted APBs and its impact on electrical transport behavior and it could potentially extend the applications of 2D materials through defect engineering to achieve the desired properties.

An Organic/Inorganic Nanocomposite of Cellulose Nanofibers and ZnO Nanorods for Highly Sensitive, Reliable, Wireless, and Wearable Multifunctional Sensor Applications.

Organic and inorganic one-dimensional nanomaterials were synthesized and combined into a nanocomposite film for a wearable sensor. Reproducible ZnO nanorod (NR) synthesis was achieved by the addition of an appropriate amount of water. Cellulose nanofibers (CNFs) were used due to their porous matrix formation. The interconnected channels of brittle ZnO NRs were well-fabricated in the flexible network of CNFs. The surface morphology, thermal, and mechanical properties of the CNF/ZnO NR nanocomposite film were characterized. The interfacial interactions between these two nanomaterials were also studied. The nanocomposite film is sufficiently flexible so that it shows no electrical resistance changes even after repeated bending tests with a minimum bending radius of 1.5 mm. In addition, ZnO NRs with different lengths were synthesized. The composite of longer ZnO NRs and CNF showed 2.8 × 103 times higher photocurrent and responsivity performance. The humidity sensing performance of the composite was also suggested. The CNF/ZnO NR film shows reasonable electrical signal changes enabling the evaluation of a calibration curve. Finally, a smart band including a CNF/ZnO NR film sensor was fabricated and connected to a smartphone by Bluetooth. These results open an avenue for developing wearable sensors by overcoming the brittleness of inorganic materials.

Torsional and Bending Properties of V Taper 2H, ProTaper NEXT, NRT, and One Shape.

Nickel-titanium (NiTi) rotary files have enabled efficient root canal preparations that maintain the canal center with fewer aberrations compared to hand files. However, NiTi rotary files are susceptible to fracture, which can thereby compromise root canal treatment. Therefore, NiTi files have been developed to enhance fracture resistance by modifying design and thermal treatment. The objective of this study was to compare the torsional fatigue resistance and bending resistance of NiTi files manufactured from different alloys and treatments. ProTaper NEXT X2 (PTN; M-wire), V taper 2H (V2H; controlled memory wire), NRT (heat-treated), and One Shape (OS; conventional alloy) instruments of tip size #25 were compared. Torsional fatigue was evaluated by embedding the 3 mm tip of each instrument (N = 10/brand) in resin and the repetitive application of torsional stress (300 rpm, 1.0 N·cm) by an endodontic motor with autostop when the file fractured. The number of loading cycles to fracture was recorded and analyzed by Kruskal-Wallis and Mann-Whitney U tests with Bonferroni's correction. Bending resistance of the instruments was tested using a cantilever bending test to the 3 mm point from the tip (N = 10/brand). The stress was measured when deflection of 3 mm was subjected and statistically analyzed with a one-way analysis of variance and Tukey's honest significance difference test (α = 0.05). V2H withstood the highest number of load applications during torsional fatigue testing (p < 0.05), followed by NRT, PTN, and OS, where the differences between NRT and PTN (p=0.035) and between PTN and OS (p=0.143) were not statistically significant. V2H showed the lowest bending stiffness, followed by NRT, PTN, and OS (p < 0.001). Thermal treatment of NiTi wire resulted in improved mechanical properties, and controlled memory wire provided improved flexibility and torsional fatigue resistance.

The therapeutic effect of cyanoacrylate on gastric variceal bleeding and factors related to clinical outcome.

BACKGROUND: Cyanoacrylate has been recommended for the treatment of gastric variceal bleeding. GOAL: We aimed to evaluate the efficacy and safety of cyanoacrylate injection therapy in patients with gastric variceal bleeding, and to identify the factors predictive of failure, rebleeding, and survival after therapy. STUDY: One hundred twenty-one patients with gastric variceal bleeding who received cyanoacrylate injections were retrospectively reviewed. RESULTS: Treatment succeeded in 110 patients (90.9%). Rebleeding and mortality rate during 4-week were 13.2% and 11.6%. A stepwise logistic regression analysis indicated that only the Child-Pugh class was an independent predictive factor of treatment failure [Child-Pugh C vs. Child-Pugh A and B, odds ratio (OR), 5.0; 95% confidence interval (CI), 1.2-19.4; P=0.025]. The actuarial probability of a 4-week absence of rebleeding and survival after the initial therapy was 86.8% and 85.1%, respectively. A stepwise logistic regression analysis showed that a Child-Pugh class C and hepatocellular carcinoma were independent predictive factors for rebleeding (OR, 7.4; 95% CI, 2.0-27.0; P=0.003 and OR, 3.3; 95% CI, 1.0-11.1; P=0.05, respectively) and mortality (OR, 7.4; 95% CI, 2.0-27.0; P=0.003 and OR, 3.3; 95% CI, 1.0-11.1; P=0.05, respectively). Only 2 cases (2.7%) with serious complications, noted as cyanoacrylate embolisms, were observed. At 1-year follow up, the actuarial probability of remaining free of bleeding was 49.0% and hepatitis B virus infection was independent predictive factor of bleeding (OR, 5.3; 95% CI, 1.4-20.0; P=0.015). CONCLUSIONS: In short-term follow-up, cyanoacrylate injection is an effective treatment method for gastric variceal bleeding and the Child-Pugh class was only independent predictive factor of treatment failure and the Child-Pugh class and the hepatocellular carcinoma were risk factors for rebleeding and survival. In long-term follow-up, the presence of hepatitis B infection was risk factor for rebleeding.

Covalent, Non-Covalent, Encapsulated Nanodrug Regulate the Fate of Intra- and Extracellular Trafficking: Impact on Cancer and Normal Cells.

Drugs need to be designed to access the designated intracellular organelle compartments in order to maximize anticancer efficacy. This study identified that covalently conjugated, non-covalent polyethylene glycol coated and encapsulated nanodrugs selectively influence drug uptake, the intracellular and extracellular trafficking of cancer cells. The types of nano conjugation modulated intracellular dynamics associated with differential impact on anti-cancer efficacy, but also induced differential cytotoxicity on cancer versus normal cells. In conclusion, this study demonstrated the importance of selecting the appropriate type of nano-conjugation for delivering organelle specific, active chemotherapeutic agents through controlled intracellular trafficking.