Polymerization-Enhanced Photophysical Performances of AIEgens for Chemo/Bio-Sensing and Therapy.

AIE polymers have been extensively researched in the fields of OLEDs, sensing, and cancer treatment since its first report in 2003, which have achieved numerous breakthroughs during the years. In comparison with small molecules, it can simultaneously combine the unique advantages of AIE materials and the polymer itself, to further enhance their corresponding photophysical performances. In this review, we enumerate and discuss the common construction strategies of AIE-active polymers and summarize the progress of research on polymerization enhancing luminescence, photosensitization, and room-temperature phosphorescence (RTP) with their related applications in chemo/bio-sensing and therapy. To conclude, we also discuss current challenges and prospects of the field for future development.

Photodynamic antibacterial application of TiO2/curcumin/hydroxypropyl-cyclodextrin and its konjac glucomannan composite films.

Although photodynamic therapy (PDT) has great advantages for the treatment of bacterial infections, photosensitizers (PSs) often have many disadvantages that limit their application. Improving the shortcomings of PSs and developing efficient PDT antimicrobial materials remain serious challenges. In this study, a nanocomposite drug (TiO2/curcumin/hydroxypropyl-cyclodextrin, TiO2/Cur/HPCD) was constructed and combined with konjac glucomannan to form composite films (TiO2/Cur/HPCD films, KTCHD films). The stabilities of TiO2 and Cur were improved in the presence of HPCD. The particle size of TiO2/Cur/HPCD was approximately 33.9 nm, and the addition of TiO2/Cur/HPCD enhanced the mechanical properties of the films. Furthermore, TiO2/Cur/HPCD and KTCHD films exhibited good biocompatibility and PDT antibacterial effects. The antibacterial rate of TiO2/Cur/HPCD was 74.46 % against MRSA at 500 µg/mL and 99.998 % against E. coli at 400 µg/mL, while it was adsorbed on the surface of bacteria to improve the effectiveness of the treatment. In addition, studies in mice confirmed that TiO2/Cur/HPCD and KTCHD films can treat bacterial infections and promote wound healing, with a highest wound healing rate of 84.6 % in the KTCHD-10 films + Light group on day 12. Overall, TiO2/Cur/HPCD is a promising nano-antibacterial agent and KTCHD films have the potential to be employed as antibacterial and environment-friendly trauma dressings.

Physical Frailty and Oral Frailty Associated with Late-Life Depression in Community-Dwelling Older Adults.

Late-life depression is a major mental health problem and constitutes a heavy public health burden. Frailty, an aging-related syndrome, is reciprocally related to depressive symptoms. This study investigated the associations of physical frailty and oral frailty with depression in older adults. This large-scale cross-sectional study included 1100 community-dwelling older adults in Taiwan. The participants completed a dental examination and questionnaires answered during personal interviews. The 15-item Geriatric Depression Scale was used to assess depression, and information on physical conditions and oral conditions was collected. Multivariable logistical regression analysis was conducted to examine associations of interest. Significant factors associated with depression were pre-physical frailty (adjusted odds ratio (aOR) = 3.61), physical frailty (aOR = 53.74), sarcopenia (aOR = 4.25), insomnia (aOR = 2.56), pre-oral frailty (aOR = 2.56), oral frailty (aOR = 4.89), dysphagia (aOR = 2.85), and xerostomia (aOR = 1.10). Depression exerted a combined effect on physical frailty and oral frailty (aOR = 36.81). Physical frailty and oral frailty were significantly associated with late-life depression in community-dwelling older adults in a dose-response manner. Developing physical and oral function interventions to prevent depression among older adults is essential.

Migration deficits of the neural crest caused by CXADR triplication in a human Down syndrome stem cell model.

Down syndrome (DS) is the most common chromosomal abnormality in live-born infants and is caused by trisomy of chromosome 21. Most individuals with DS display craniofacial dysmorphology, including reduced sizes of the skull, maxilla, and mandible. However, the underlying pathogenesis remains largely unknown. Since the craniofacial skeleton is mainly formed by the neural crest, whether neural crest developmental defects are involved in the craniofacial anomalies of individuals with DS needs to be investigated. Here, we successfully derived DS-specific human induced pluripotent stem cells (hiPSCs) using a Sendai virus vector. When DS-hiPSCs were induced to differentiate into the neural crest, we found that trisomy 21 (T21) did not influence cell proliferation or apoptosis. However, the migratory ability of differentiated cells was significantly compromised, thus resulting in a substantially lower number of postmigratory cranial neural crest stem cells (NCSCs) in the DS group than in the control group. We further discovered that the migration defects could be partially attributed to the triplication of the coxsackievirus and adenovirus receptor gene (CXADR; an adhesion protein) in the DS group cells, since knockdown of CXADR substantially recovered the cell migratory ability and generation of postmigratory NCSCs in the DS group. Thus, the migratory deficits of neural crest cells may be an underlying cause of craniofacial dysmorphology in individuals with DS, which may suggest potential targets for therapeutic intervention to ameliorate craniofacial or other neural crest-related anomalies in DS.

Dental Treatment Needs and Related Risk Factors among School Children with Special Needs in Taiwan.

The purpose of this study was to assess dental treatment needs (TNs) and related risk factors of children with disabilities (CD). This cross-sectional study recruited 484 CD, 6 to 12 years of age, from 10 special education schools in Taiwan. Dental status and TNs were examined and evaluated by well-trained dentists and based on the criteria set by the World Health Organization (1997). The results indicated that 61.78% required restorative dental treatment due to their dental caries. On average, each participant had 2.72 teeth that required treatment, and 6.38 surfaces required restoration. One-quarter of the participants (24.79%) required 1- or 2-surface restoration, and one out of three (36.98%) had more complex TNs (including 3 or more surfaces to be filled, pulp care, extraction, and more specialized care). The significant risk factors associated with restorative TNs among CD were those whose parents had lower socioeconomic status, frequent sweets intake, insufficient tooth-brushing ability, and poor oral health. Most of the CD had extensive unmet TNs for their caries and required complex treatment to recover the function of their teeth. Encouraging parents/caregivers to take their children for dental treatment, promoting awareness of the importance of dental hygiene, giving assistance to brushing their teeth after eating, and controlling and/or modifying sweet diet habits are necessary to reduce CD's dental caries, especially those with lower socioeconomic status parents/caregivers.

The Effectiveness of a Board Game-Based Oral Hygiene Education Program on Oral Hygiene Knowledge and Plaque Index of Adults with Intellectual Disability: A Pilot Study.

An oral hygiene board game was designed as an intervention tool and applied to explore the effectiveness for the oral health related knowledge (OHK) score and plaque index (PI) of adults with intellectual disability (ID). This one-group pre/post-test design study was conducted in a residential long-term care facility for 42 participants. The study had one pre-test (baseline) and three post-tests evaluated in both control and intervention stages, respectively. The participants participated in a 60-min oral hygiene board game twice a week during the intervention stage. Total OHK score and PI of the participants were recorded to determine the effectiveness of intervention. There were no differences in OHK score and PI between the two stages at baseline. The results in intervention stage demonstrated a significant gradual increase and reduction in the OHK score when compared with the control stage. A statistically significant improvement in the OHK score and PI (42.29% and -33.28%, respectively) at the end of intervention between two stages was recorded. This study proved a board game is deemed an effective education method applicable to promote the OHK and skills of ID adults.

A mechanical stability enhanced luminescence lanthanide MOF test strip encapsulated with polymer net for detecting picric acid and macrodantin.

The improper use of organic explosives and antibiotics have brought serious threats to the public health and the environmental safety, exploiting cost-effective and handy luminescent sensors with water stability and high selectivity in monitoring and detecting these hazardous substances are of utmost importance. Herein, we developed a simple yet powerful luminescent test strip sensor in a facile way. As for fabricating this test strip, the filter paper used for filtering lanthanide MOF (Ln-MOF) of [Tb(HIP)(H2O)5]·(H2O)·(HIP)1/2 (Tb-HIP, where HIP is 5-hydroxyisophthalate) powders was firstly recycled, and encapsulated with poly(methyl methacrylate) (PMMA) polymer net. The as-fabricated Tb-HIP test strips exhibit enhanced mechanical stability than the un-encapsulated ones, and show characteristic green emission of Tb3+. These test strips can behave as promising highly selective luminescent probes for picric acid (PA) and macrodantin (MDT) even existence of relevant potentially competing analytes. The detection limit for PA is 0.26 µM, and for MDT is 0.21 µM. In addition, the sensors can be successfully applied to detect PA in the river water samples as well as MDT in serum samples with satisfactory results. More importantly, the Tb-HIP test strips are highly efficient, recyclable luminescence sensors to detect PA and MDT.

O2-Cu/ZIF-8@Ce6/ZIF-8@F127 Composite as a Tumor Microenvironment-Responsive Nanoplatform with Enhanced Photo-/Chemodynamic Antitumor Efficacy.

Hypoxia and overexpression of glutathione (GSH) are typical characteristics of the tumor microenvironment, which severely hinders cancer treatments. Here, we design a novel biodegradable therapeutic system, O2-Cu/ZIF-8@Ce6/ZIF-8@F127 (OCZCF), to simultaneously achieve GSH depletion and O2-enhanced combination therapy. Notably, the doped Cu2+ doubles the O2 storage capacity of the ZIF-8 matrix, which makes OCZCF an excellent pH-sensitive O2 reservoir for conquering tumor hypoxia, enhancing the photodynamic therapy (PDT) efficiency of chlorin e6 (Ce6) under 650 nm laser irradiation. Moreover, the released Cu2+ can act as a smart reactive oxygen species protector by consuming intracellular GSH. The byproduct Cu+ will undergo highly efficient Fenton-like reaction to achieve chemodynamic therapy (CDT) in the presence of abundant H2O2. The accompanying O2 will further alleviate hypoxia. The in vitro and in vivo experimental data indicate that OCZCF could cause remarkable tumor inhibition through enhanced synergetic PDT and CDT, which may open up a new path for cancer therapy.

Construction of Hierarchical Polymer Brushes on Upconversion Nanoparticles via NIR-Light-Initiated RAFT Polymerization.

Photoinduced reversible addition-fragmentation chain transfer (RAFT) polymerization generally adopts high-energy ultraviolet (UV) or blue light. In combination with photoredox catalyst, the excitation light wavelength was extended to the visible and even near-infrared (NIR) region for photoinduced electron transfer RAFT polymerization. In this report, we introduce for the first time a surface NIR-light-initiated RAFT polymerization on upconversion nanoparticles (UCNPs) without adding any photocatalyst and construct a functional inorganic core/polymer shell nanohybrid for application in cancer theranostics. The multilayer core-shell UCNPs (NaYF4:Yb/Tm@NaYbF4:Gd@NaNdF4:Yb@NaYF4), with surface anchorings of chain transfer agents, can serve as efficient NIR-to-UV light transducers for initiating the RAFT polymerization. A hierarchical double block copolymer brush, consisting of poly(acrylic acid) (PAA) and poly(oligo(ethylene oxide)methacrylate-co-2-(2-methoxy-ethoxy)ethyl methacrylate) (PEG for short), was grafted from the surface in sequence. The targeting arginine-glycine-aspartic (RGD) peptide was modified at the end of the copolymer through the trithiolcarbonate end group. After loading of doxorubicin, the UCNPs@PAA-b-PEG-RGD exhibited an enhanced U87MG cancer cell uptake efficiency and cytotoxicity. Besides, the unique upconversion luminescence of the nanohybrids was used for the autofluoresence-free cell imaging and labeling. Therefore, our strategy verified that UCNPs could efficiently activate RAFT polymerization by NIR photoirradiation and construct the complex nanohybrids, exhibiting prospective biomedical applications due to the low phototoxicity and deep penetration of NIR light.

Preparation of insulin-loaded PLA/PLGA microcapsules by a novel membrane emulsification method and its release in vitro.

Uniform-sized biodegradable PLA/PLGA microcapsules loading recombinant human insulin (rhI) were successfully prepared by combining a Shirasu Porous Glass (SPG) membrane emulsification technique and a double emulsion-evaporation method. An aqueous phase containing rhI was used as the inner water phase (w1), and PLA/PLGA and Arlacel 83 were dissolved in a mixture solvent of dichloromethane (DCM) and toluene, which was used as the oil phase (o). These two solutions were emulsified by a homogenizer to form a w1/o primary emulsion. The primary emulsion was permeated through the uniform pores of a SPG membrane into an outer water phase by the pressure of nitrogen gas to form the uniform w1/o/w2 droplets. The solid polymer microcapsules were obtained by simply evaporating solvent from droplets. Various factors of the preparation process influencing the drug encapsulation efficiency and the drug cumulative release were investigated systemically. The results indicated that the drug encapsulation efficiency and the cumulative release were affected by the PLA/PLGA ratio, NaCl concentration in outer water phase, the inner water phase volume, rhI-loading amount, pH-value in outer water phase and the size of microcapsules. By optimizing the preparation process, the drug encapsulation efficiency was high up to 91.82%. The unique advantage of preparing drug-loaded microcapsules by membrane emulsification technique is that the size of microcapsules can be controlled accurately, and thus the drug cumulative release profile can be adjusted just by changing the size of microcapsules. Moreover, much higher encapsulation efficiency can be obtained when compared with the conventional mechanical stirring method.

Long-term effect of ropivacaine nanoparticles for sciatic nerve block on postoperative pain in rats.

PURPOSE: The analgesic effect of ropivacaine (Rop) for nerve block lasts only ~3-6 hours for single use. The aim of this study was to develop long-acting regional anesthetic Rop nanoparticles and investigate the effects of sciatic nerve block on postoperative pain in rats. MATERIALS AND METHODS: Rop nanoparticles were developed using polyethylene glycol-co-polylactic acid (PELA). One hundred and twenty adult male Wistar rats were randomly divided into four groups (n=30, each): Con (control group; 0.9% saline, 200 µL), PELA (PELA group; 10 mg), Rop (Rop group; 0.5%, 200 µL), and Rop-PELA (Rop-PELA group; 10%, 10 mg). Another 12 rats were used for the detection of Rop concentration in plasma. The mechanical withdrawal threshold and thermal withdrawal latency were measured at 2 hours, 4 hours, 8 hours, 1 day, 2 days, 3 days, 5 days, and 7 days after incision. The expression of c-FOS was determined by immunohistochemistry at 2 hours, 8 hours, 48 hours, and 7 days. Nerve and organ toxicities were also evaluated at 7 days. RESULTS: The duration of Rop absorption in the plasma of the Rop-PELA group was longer (>8 hours) than that of the Rop group (4 hours). Mechanical withdrawal threshold and thermal withdrawal latency in the Rop-PELA group were higher than that in other groups (4 hours-3 days). c-FOS expression in the Rop-PELA group was lower than that in the control group at 2 hours, 8 hours, and 48 hours and lower than that in the Rop group at 8 hours and 48 hours after paw incision. Slight foreign body reactions were observed surrounding the sciatic nerve at 7 days. No obvious pathophysiological change was found in the major organs after Rop-PELA administration at 7 days. CONCLUSION: Rop-PELA provides an effective analgesia for nerve block over 3 days after single administration, and the analgesic mechanism might be mediated by the regulation of spinal c-FOS expression. However, its potential long-term tissue toxicity needs to be further investigated.

Rational design of a comprehensive cancer therapy platform using temperature-sensitive polymer grafted hollow gold nanospheres: simultaneous chemo/photothermal/photodynamic therapy triggered by a 650 nm laser with enhanced anti-tumor efficacy.

Combining multi-model treatments within one single system has attracted great interest for the purpose of synergistic therapy. In this paper, hollow gold nanospheres (HAuNs) coated with a temperature-sensitive polymer, poly(oligo(ethylene oxide) methacrylate-co-2-(2-methoxyethoxy)ethyl methacrylate) (p(OEGMA-co-MEMA)), co-loaded with DOX and a photosensitizer Chlorin e6 (Ce6) were successfully synthesized. As high as 58% DOX and 6% Ce6 by weight could be loaded onto the HAuNs-p(OEGMA-co-MEMA) nanocomposites. The grafting polymer brushes outside the HAuNs play the role of "gate molecules" for controlled drug release by 650 nm laser radiation owing to the temperature-sensitive property of the polymer and the photothermal effect of HAuNs. The HAuNs-p(OEGMA-co-MEMA)-Ce6-DOX nanocomposites with 650 nm laser radiation show effective inhibition of cancer cells in vitro and enhanced anti-tumor efficacy in vivo. In contrast, control groups without laser radiation show little cytotoxicity. The nanocomposite demonstrates a way of "killing three birds with one stone", that is, chemotherapy, photothermal and photodynamic therapy are triggered simultaneously by the 650 nm laser stimulation. Therefore, the nanocomposites show the great advantages of multi-modal synergistic effects for cancer therapy by a remote-controlled laser stimulus.

Multifunctional NaYF4:Yb, Er@mSiO2@Fe3O4-PEG nanoparticles for UCL/MR bioimaging and magnetically targeted drug delivery.

A low toxic multifunctional nanoplatform, integrating both mutimodal diagnosis methods and antitumor therapy, is highly desirable to assure its antitumor efficiency. In this work, we show a convenient and adjustable synthesis of multifunctional nanoparticles NaYF4:Yb, Er@mSiO2@Fe3O4-PEG (MFNPs) based on different sizes of up-conversion nanoparticles (UCNPs). With strong up-conversion fluorescence offered by UCNPs, superparamagnetism properties attributed to Fe3O4 nanoparticles and porous structure coming from the mesoporous SiO2 shell, the as-obtained MFNPs can be utilized not only as a contrast agent for dual modal up-conversion luminescence (UCL)/magnetic resonance (MR) bio-imaging, but can also achieve an effective magnetically targeted antitumor chemotherapy both in vitro and in vivo. Furthermore, the UCL intensity of UCNPs and the magnetic properties of Fe3O4 in the MFNPs were carefully balanced. Silica coating and further PEG modifying can improve the hydrophilicity and biocompatibility of the as-synthesized MFNPs, which was confirmed by the in vitro/in vivo biocompatibility and in vivo long-time bio-distributions tests. Those results revealed that the UCNPs based magnetically targeted drug carrier system we synthesized has great promise in the future for multimodal bio-imaging and targeted cancer therapy.

Core-shell structured luminescent and mesoporous ß-NaYF4:Ce3+/Tb3+@mSiO2-PEG nanospheres for anti-cancer drug delivery.

Multifunctional nanocomposites integrating mesoporous and luminescence properties into a single entity are synthesized via a facile and effective approach. Oleic acid capped ß-NaYF4:Ce(3+)/Tb(3+) nanoparticles (NPs) are transferred into aqueous solution by cetyltrimethylammonium bromide (CTAB) surfactants, and further encapsulated with uniform mesoporous silica shell followed by the surface modification with poly(ethylene glycol) (PEG), leading to the formation of water-dispersible and biocompatible core-shell structured ß-NaYF4:Ce(3+)/Tb(3+)@mSiO2-PEG (denoted as NPs@mSiO2-PEG) nanospheres. The as-synthesized nanospheres show a typical mesoporous structure and a green emission under UV irradiation. Doxorubicin hydrochloride (DOX), a widely used anti-cancer drug, is used as a model drug to evaluate the loading and controlled release behaviors of the NPs@mSiO2-PEG in phosphoric acidic buffer solutions (PBS) at different pH values (pH = 7.4 and 5.0). The composite carriers provide a pH-sensitive drug release pattern and the drug releases faster under lower pH value. The endocytosis process of fluorescein isothiocyanate (FITC)-labelled nanospheres is characterized using flow cytometry and confocal laser scanning microscopy (CLSM) against A549 cells. The in vitro cytotoxic effect against A549 cells of the DOX-loaded carriers is investigated in detail. In addition, the extent of drug release can be monitored by the variation of photoluminescence (PL) intensity of ß-NaYF4:Ce(3+)/Tb(3+). Considering the good biocompatibility and pH-dependent drug release pattern, such core-shell structured luminescent NPs@mSiO2-PEG nanospheres have potential applications in controlled drug delivery.

Electrospinning preparation and drug delivery properties of Eu3+/Tb3+ doped mesoporous bioactive glass nanofibers.

Luminescent Eu(3+)/Tb(3+) doped mesoporous bioactive glass nanofibers (MBGNFs) with average diameter of 100-120 nm were fabricated by electrospinning method. Pluronic P123 and N-cetyltrimethylammonium bromide (CTAB) were used as co-surfactants to generate porous structure of the nanofibers. N(2) adsorption-desorption measurement reveals that the MBGNF:Eu(3+) have a surface area of 188 m(2) g(-1), a pore volume of 0.246 cm(3) g(-1) and average pore size of 4.17 nm, and the MBGNF:Tb(3+) have a surface area of 171 m(2) g(-1), a pore volume of 0.186 cm(3) g(-1) and average pore size of 3.65 nm. Photoluminescence measurements reveal that the MBGNF:Eu(3+) show strong red emission dominated by the (5)D(0)→(7)F(2) transition of Eu(3+) at 614 nm with a lifetime of 1.356 ms, and MBGNF:Tb(3+) show strong green emission dominated by the (5)D(4)→(7)F(5) transition of Tb(3+) at 544 nm with a lifetime of 1.982 ms. The biocompatibility tests on L929 fibroblast cells using MTT assay reveal low cytotoxicity of MBGNF. These luminescent nanofibers show sustained release properties for ibuprofen (IBU) in vitro. The emission intensities of Eu(3+) in the drug delivery system vary with the released amount of IBU, thus making the drug release be easily tracked and monitored by the change of the luminescence intensity.

Monodisperse core-shell structured up-conversion Yb(OH)CO3@YbPO4:Er³+ hollow spheres as drug carriers.

In this work, we report a facile solution-phase synthesis of monodisperse core-shell structured Yb(OH)CO3@YbPO4 hollow spheres (size around 380 nm) by utilizing the colloidal sphere of Yb(OH)CO3 as the sacrificial template via the Kirkendall effect. The Er³+ doped Yb(OH)CO3@YbPO4 core-shell hollow spheres can be prepared similarly, which exhibit strong green emission under 980 nm NIR laser excitation even after loading with drug molecules. Most importantly, the sample can be used as an effective drug delivery carrier. The biocompatibility test on L929 fibroblast cells using MTT assay reveals low cytotoxicity of the system. A typical anticancer drug, doxorubicin hydrochloride (DOX), is used for drug loading, and the release properties, cytotoxicity, uptake behavior and therapeutic effects were examined. It is found that DOX is shuttled into cell by core-shell hollow spheres carrier and released inside cells after endocytosis, and the DOX-loaded spheres exhibited greater cytotoxicity than free DOX. These results indicate that the core-shell Er³+ doped Yb(OH)CO3@YbPO4 hollow spheres have potential for drug loading and delivery into cancer cells to induce cell death.