Cu-In-S/ZnS:Gd3+ quantum dots with isolated fluorescent and paramagnetic modules for dual-modality imaging in vivo.

Gd3+-doped quantum dots (QDs) have been widely used as small-sized bifunctional contrast agents for fluorescence/magnetic resonance (FL/MR) dual-modality imaging. However, Gd3+ doping will always compromise the FL of host QDs. Therefore, balancing the Gd3+ doping and the optical properties of QDs is crucial for constructing high-performance bifunctional nanoprobes. Additionally, most paramagnetic QDs are synthesized in the organic phase and need to be transferred to the aqueous phase for bioimaging. Herein, ingeniously designed shell-doped Cu-In-S/ZnS:Gd3+ QDs have been prepared in the aqueous phase. It has been demonstrated that isolating paramagnetic Gd3+ from fluorescent Cu-In-S core via doping Gd3+ into ZnS shell not only avoided the decrease of FL quantum yield (QY), but also ensured the water accessibility of paramagnetic Gd3+ ions, by which the FL QY and r1 relaxivity of Cu-In-S/ZnS:Gd3+ QDs achieved as much as 15.6% and 15.33 mM-1·s-1, respectively. These high-performance QDs with excellent stability, low biotoxicity, and good tumor permeability were successfully applied for in vivo tumor FL/MR dual-modality imaging, and have shown significant potential in the precision detection and diagnosis of diseases.

Reversible covalent nanoassemblies for augmented nuclear drug translocation in drug resistance tumor.

The drug efflux by P-glycoprotein (P-gp) is the primary contributor of multidrug resistance (MDR), which eventually generates insufficient nuclear drug accumulation and chemotherapy failure. In this paper, reversible covalent nanoassemblies on the basis of catechol-functionalized methoxy poly (ethylene glycol) (mPEG-dop) and phenylboronic acid-modified cholesterol (Chol-PBA) are successfully synthesized for delivery of both doxorubicin (DOX, anti-cancer drug) and tariquidar (TQR, P-glycoprotein inhibitor), which shows efficient nuclear DOX accumulation for overcoming tumor MDR. Through naturally forming phenylboronate linkage in physiological circumstances, Chol-PBA is able to bond with mPEG-dop. The resulting conjugates (PC) could self-assemble into reversible covalent nanoassemblies by dialysis method, and transmission electron microscopy analysis reveals the PC distributes in nano-scaled spherical particles before and after drug encapsulation. Under the assistance of Chol, PC can enter into lysosome of tumor cells via low-density lipoprotein (LDL) receptor-mediated endocytosis. Then the loaded TQR and DOX are released in acidic lysosomal compartments, which inhibit P-gp mediated efflux and elevate nuclear accumulation of DOX, respectively. At last, this drug loaded PC nanoassemblies show significant tumor suppression efficacy in multidrug-resistant tumor models, which suggests great potential for addressing MDR in cancer therapy.

Pathway of Diatoms Enter Experimental Rabbits through the Lymphatic System of the Digestive Tract.

OBJECTIVES: To study whether diatoms can enter the body through the lymphatic system of the digestive tract. METHODS: Twenty experimental rabbits were divided into the test group and the control group randomly, and intragastric administration was performed with 20 mL water sample from the Pearl River and 20 mL ultrapure water, respectively. After 30 min, lymph, lungs, livers and kidneys were extracted for the diatom test. The concentration, size and type of diatoms were recorded. RESULTS: The concentration of diatoms of the test group was higher than that of the control group (P<0.05). In the test group, Stephanodiscus, Coscinodiscus, Cyclotella, Melosira, Nitzschia, Synedra, Cymbella, and Navicula were detected; in the control group, Stephanodiscus, Coscinodiscus and Cyclotella were detected. The long diameter and the short diameter of diatoms of the test group were higher than those of the control group (P<0.05). In the test group, 1-2 diatoms were detected in 3 lung samples and 2 liver samples, which were Stephanodiscus or Cyclotella, and no diatoms were detected in the kidney samples; in the control group, 1-2 diatoms were detected in 2 lung samples and 3 liver samples, which were Stephanodiscus or Coscinodiscus, and no diatoms were detected in the kidney samples. CONCLUSIONS: Diatoms can enter the body through the lymphatic fluid, which is one of the reasons for the presence of diatoms in tissues and organs of non-drowning cadavers.

Effects of Digestive Temperature and Time on Diatom Test.

OBJECTIVES: To study the effects of temperature and time for diatoms digestion and find out suitable digestive temperature and time. METHODS: Eighty pieces of liver tissues were collected, each piece of tissue was 2 g, and 2 mL Pearl River water was added to each piece of tissue. The digestion temperature was set at 100 ℃, 120 ℃, 140 ℃, 160 ℃, 180 ℃ and the digestion time was set at 40, 50, 60, 70, 80 min. The liver tissue and water mixture were divided into 8 portions in each group. All the samples were tested by microwave digestive - vacuum filtration - automated scanning electron microscopy method. The quantity of diatom recovered and the quality of residue on the membrane were recorded. RESULTS: When the digestion time was set to 60 min, there were statistically significant differences in the number of diatoms recovered at different temperatures (P<0.05). The maximum number of diatoms recovered was (28 797.50±6 009.67) at 140 ℃, and the minimum residue was (0.60±0.28) mg at 180 ℃. When the digestion temperature was set at 140 ℃, there were statistically significant differences in the number of diatoms recovered at different digestion times (P<0.05). The number of diatoms recovered was the highest at 40 min, it was up to (20 650.88±1 950.29), and the residue quality of each group had no statistical significance among different digestion time groups(P>0.05). CONCLUSIONS: The effect of diatom digestion is related to temperature and time. When the digestion temperature was 140 ℃ and the digestion time was 40, 50 and 60 min, it is favorable for diatom test.

Application of Diatoms Quantitative Analysis in the Diagnosis of Drowning.

OBJECTIVES: To retrospectively analyze diatom test cases of corpses in water and discuss the value of quantitative analysis of diatoms in the diagnosis of drowning. METHODS: A total of 490 cases of water-related death were collected. They were divided into drowning group and postmortem immersion group according to the cause of death. Diatoms in lung, liver, kidney tissue and water sample were analyzed quantitatively by microwave digestion-vacuum filtration-automated scanning electron microscopy (MD-VF-Auto SEM) method. The ratios of content of diatoms in lung tissue and water sample (CL/CD) were calculated. RESULTS: The results of diatom test for three organs (lung, liver and kidney) were all positive in 400 cases (85.5%); the content of diatom in lung, liver, kidney tissues, and water samples of drowning group were (113 235.9±317 868.1), (26.7±75.6), (23.3±52.2) and (12 113.3±21 760.0) cells/10 g, respectively; the species of diatom were (7.5±2.8), (2.6±1.9), (2.9±2.1) and (8.9±3.0) types, respectively; the CL/CD of drowning group and postmortem immersion group were (100.6±830.7) and (0.3±0.4), respectively. CONCLUSIONS: Quantitative analysis of diatoms can provide supportive evidence for the diagnosis of drowning, and the parameter CL/CD can be introduced into the analysis to make a more accurate diagnosis of drowning.

Small-sized copolymeric nanoparticles for tumor penetration and intracellular drug release.

Poor solid-tumor penetration of nanocarriers limits the drug efficacy. Herein, small-sized copolymeric nanoparticles are prepared for delivering the chemotherapeutic drug DOX into solid tumors deeply and releasing the drug effectively. These small-sized copolymeric nanoparticles represent substantial potential for clinical translation.