Recent progress of polymeric microneedle-assisted long-acting transdermal drug delivery.

Microneedle (MN)-assisted drug delivery technology has gained increasing attention over the past two decades. Its advantages of self-management and being minimally invasive could allow this technology to be an alternative to hypodermic needles. MNs can penetrate the stratum corneum and deliver active ingredients to the body through the dermal tissue in a controlled and sustained release. Long-acting polymeric MNs can reduce administration frequency to improve patient compliance and therapeutic outcomes, especially in the management of chronic diseases. In addition, long-acting MNs could avoid gastrointestinal reactions and reduce side effects, which has potential value for clinical application. In this paper, advances in design strategies and applications of long-acting polymeric MNs are reviewed. We also discuss the challenges in scale manufacture and regulations of polymeric MN systems. These two aspects will accelerate the effective clinical translation of MN products.

Construction of aggregation-induced emission photosensitizers through host-guest interactions for photooxidation reaction and light-harvesting.

In the present work, we have designed and synthesized a triphenylamine modified cyanophenylenevinylene derivative (TPCI), which can self-assembly with cucurbit[6]uril (CB[6]) and cucurbit[8]uril (CB[8]) through host-guest interactions to form supramolecular complexes (TPCI-CB[6]) and supramolecular polymers (TPCI-CB[8]) in the aqueous solution. The supramolecular assemblies of TPCI-CB[6] and TPCI-CB[8] not only exhibited high singlet oxygen (1O2) production efficiency as photosensitizers, but also realized the application in the construction of artificial light-harvesting systems due to the excellent fluorescence properties in the aqueous solution. The production efficiency of 1O2 has been effectively improved after the addition of CB[6] and CB[8] for TPCI, which were applied as efficient photosensitizers in the photooxidation reactions of thioanisole and its derivatives with the highest yield of 98% in the aqueous solution. The excellent fluorescence properties of TPCI-CB[6] and TPCI-CB[8] can be used as energy donors in artificial light-harvesting systems with energy acceptors sulforhodamine 101 (SR101) and cyanine dye 5 (Cy5), in which one-step energy transfer processes of TPCI-CB[6]+SR101 and TPCI-CB[8]+Cy5, and a two-step sequential energy transfer process of TPCI-CB[6]+SR101+Cy5 were constructed to simulate the natural photosynthesis system.

Oncocyte Membrane-Camouflaged Multi-Stimuli-Responsive Nanohybrids for Synergistic Amplification of Tumor Oxidative Stresses and Photothermal Enhanced Cancer Therapy.

The combination of various therapeutic modalities has received considerable attention for improving antitumor performance. Herein, an innovative nanohybrid, namely CaO2@FePt-DOX@PDA@CM (CFDPM), was developed for synergistic chemotherapy/chemodynamic therapy/Ca2+ overloading-mediated amplification of tumor oxidative stress and photothermal enhanced cancer therapy. Camouflage of the 4T1 cell membrane enabled CFDPM to escape the immune surveillance and accumulate in the tumor tissue. Ca2+, released from CaO2, could lead to mitochondrial dysfunction and facilitate the production of reactive oxygen species to amplify intracellular oxidative stress. Meanwhile, the increase of H2O2 concentration could enhance the efficiency of the chemodynamic therapy (CDT). Moreover, the hypoxic condition could be alleviated remarkably, which is attributed to the sufficient O2 supply by CaO2, resulting in the suppression of drug resistance and promotion of the chemotherapeutic effect. The nanohybrids involving Ca2+ overloading/CDT/chemotherapy could synergistically amplify the tumor oxidative stresses and remarkably aggravate the death of cancer cells. Significantly, the excellent photothermal conversion performance of CFDPM could further promote the tumoricidal effect. The in vitro and in vivo studies revealed that CFDPM could effectively advance the therapeutic efficiency via the cooperation of various therapeutic modalities to optimize their individual virtue, which would open a valuable avenue for effective cancer treatment.

An analysis of the heavy element distribution in edible tissues of the swimming crab (Portunus trituberculatus) from Shandong Province, China and its human consumption risk.

This study evaluated the food safety of the swimming crab (Portunus trituberculatus) found in Shandong Province, China and obtained information on possible edible parts and gender differences. White and brown muscle samples from 108 swimming crabs were collected from seven cities along the eastern coastline of Shandong Province and analyzed for levels of Cu, Zn, Ni, As, Fe, Mn, Cr, Se, Cd, and Pb. There were significant differences in the metal concentrations among different edible muscles. High concentrations of Zn, Mn, and Cr were found in leg and claw meat while Fe, Cu, Ni, As, Cd, Pb, and Se were predominantly found in the hepatopancreas and gonads. Gender differences were found only for Fe and Zn. Based on the estimated daily intake (EDI), target hazard quotient (THQ), total target hazard quotient (TTHQ), and the permissible safety limits prescribed by various agencies, consumption of the swimming crab is considered safe.

Comparison of trace element concentrations in freshwater fish and marine fish consumed in Shandong Province, China, and their potential risks to human health.

This study provides the primary data of ten trace element concentrations from four highly consumed cultured freshwater fish species in comparison to six marine fish collected from markets of the Shandong province, China, and evaluates the potential human health risks from consuming these fish. A significant difference in five metal concentrations (Cr, As, Se, Cd, Pb) was found between freshwater and marine fish. With the exception of chromium, the other four element contents in marine fish were higher than those in freshwater fish. According to estimated daily intake (EDI), target hazard quotient (THQ), total target hazard quotient (TTHQ), and the permissible safety limits prescribed by various agencies, consumption of the examined fish species is safe for human health. However, chromium in freshwater fish and arsenic in marine fish should still be a cause for concern in terms of human health, especially for fisher folk communities and populations that frequently consume fish.

Trace elements concentrations in squids consumed in Shandong Province China and their associated risks to the human health.

Determination of ten metal levels in 160 squid samples caught from offshore and the oceanic fishing locations by ICP-MS was made. The mean metal concentration in the squid muscles decreasing in the order of: Zn, Fe, Cu, As, Mn, Se, Cd, Pb, Cr and Ni. Metal concentrations in the squids were assessed for human uses according to provisional tolerable weekly intake (PTWI) and provisional tolerable daily intake (PTDI)·The estimated hazard quotients for the individual metals from squids were found in accordance to the following sequence: As > Cd > Cu > Se > Cr > Zn > Pb > Fe > Mn > Ni, with the greatest hazard upon human health coming primarily from As (1.34 < HQ < 1.73 in the Loliginidae from two offshore sampling sites and the Humboldt squid from the eastern Pacific Ocean). In regards to the heavy metal pollution of the coastal sea areas, the squids captured from offshore sites might pose a higher potential health risk to consumers compared to those from the ocean.

Quantitative analysis and health risk assessment of polycyclic aromatic hydrocarbons in edible vegetable oils marketed in Shandong of China.

This work studies on the quantitative analysis and health risk assessment of polycyclic aromatic hydrocarbons (PAHs) in edible vegetable oils in Shandong, China. The concentrations of 15 PAHs in 242 samples were determined by high performance liquid chromatography coupled with fluorescence detection. The results indicated that the mean concentration of 15 PAHs in oil samples was 54.37 µg kg(-1). Low molecular weight PAH compounds were the predominant contamination. Especially, the carcinogenic benzo(a)pyrene (BaP) was detected at a mean concentration of 1.28 µg kg(-1), which was lower than the limit of European Union and China. A preliminary evaluation of human health risk assessment for PAHs was accomplished using BaP toxic equivalency factors and the incremental lifetime cancer risk (ILCR). The ILCR values for children, adolescents, adults, and seniors were all larger than 1 × 10(-6), indicating a high potential carcinogenic risk on the dietary exposed populations.

Development of a ratiometric time-resolved luminescence sensor for pH based on lanthanide complexes.

Time-resolved luminescence bioassay technique using lanthanide complexes as luminescent probes/sensors has shown great utilities in clinical diagnostics and biotechnology discoveries. In this work, a novel terpyridine polyacid derivative that can form highly stable complexes with lanthanide ions in aqueous media, (4'-hydroxy-2,2':6',2''-terpyridine-6,6''-diyl) bis(methylenenitrilo) tetrakis(acetic acid) (HTTA), was designed and synthesized for developing time-resolved luminescence pH sensors based on its Eu(3+) and Tb(3+) complexes. The luminescence characterization results reveal that the luminescence intensity of HTTA-Eu(3+) is strongly dependent on the pH values in weakly acidic to neutral media (pK(a) = 5.8, pH 4.8-7.5), while that of HTTA-Tb(3+) is pH-independent. This unique luminescence response allows the mixture of HTTA-Eu(3+) and HTTA-Tb(3+) (the HTTA-Eu(3+)/Tb(3+) mixture) to be used as a ratiometric luminescence sensor for the time-resolved luminescence detection of pH with the intensity ratio of its Tb(3+) emission at 540 nm to its Eu(3+) emission at 610 nm, I(540 nm)/I(610 nm), as a signal. Moreover, the UV absorption spectrum changes of the HTTA-Eu(3+)/Tb(3+) mixture at different pHs (pH 4.0-7.0) also display a ratiometric response to the pH changes with the ratio of absorbance at 290 nm to that at 325 nm, A(290 nm)/A(325 nm), as a signal. This feature enables the HTTA-Eu(3+)/Tb(3+) mixture to have an additional function for the pH detection with the absorption spectrometry technique. For loading the complexes into the living cells, the acetoxymethyl ester of HTTA was synthesized and used for loading HTTA-Eu(3+) and HTTA-Tb(3+) into the cultured HeLa cells. The luminescence imaging results demonstrated the practical utility of the new sensor for the time-resolved luminescence cell imaging application.