Time-dependent hormesis transfer from five high-frequency personal care product components to mixtures.

There is potential for personal care products (PCPs) components and mixtures to induce hormesis. How hormesis is related to time and transmitted from components to mixtures are not clear. In this paper, we conducted determination of components in 16 PCP products and then ran frequent itemset mining on the component data. Five high-frequency components (HFCs), betaine (BET), 1,3-butanediol (BUT), ethylenediaminetetraacetic acid disodium salt (EDTA), glycerol (GLO), and phenoxyethanol (POE), and 14 mixtures were identified. For each mixture system, one mixture ray with the actual mixture ratios in the products was selected. Time-dependent microplate toxicity analysis was used to test the luminescence inhibition toxicity of five HFCs and 14 mixture rays to Vibrio qinghaiensis sp.-Q67 at 12 concentration gradients and eight exposure times. It is showed that BET, EDTA, POE, and 13 mixture rays containing at least one J-type component showed time-dependent hormesis. Characteristic parameters used to describe hormesis revealed that the absolute value of the maximum stimulatory effect (|Emin|) generally increased with time. Notably, mixtures composed of POE and S-type components showed greater |Emin| than POE alone at the same time. Importantly, the maximum stimulatory effective concentration, NOEC/the zero effective concentration point, and EC50 remained relatively stable. Nine hormesis transmission phenomena were observed in different mixture rays. While all mixtures primarily exhibited additive action, varying degrees of synergism and antagonism were noted in binary mixtures, with no strong synergism or antagonism observed in ternary and quaternary mixtures. These findings offer valuable insights for the screening of HFCs and their mixtures, as well as the study of hormesis transmission in personal care products.

Customizing biomimetic surface attributes of dendritic lipopeptide nanoplatforms for extended circulation.

The pressing demand for innovative approaches to create delivery systems with heightened drug loading and prolonged circulation has spurred numerous efforts, yielding some successes but accompanied by constraints. Our study proposes employing dendritic lipopeptide with precisely balanced opposing charges to extend blood residency for biomimetic nanoplatforms. Neutrally mixed-charged zwitterionic nanoparticles (NNPs) achieved a notable 19 % simvastatin loading content and kept stable even after one-month storage at 4 °C. These nanoplatforms demonstrated low cytotoxicity in NIH-3T3 and L02 cells and negligible hemolysis (<5 %). NNPs inhibited protein adhesion (>95 %) from positively and negatively charged sources through surface hydration. In comparison to positively charged CNPs, NNPs demonstrated an 86 % decrease in phagocytic rate by BMDMs, highlighting their efficacy. Importantly, NNPs showed prolonged circulation compared to CNPs and free simvastatin. These findings highlight the potential of this biomimetic nanoplatform for future therapeutic applications with enhanced drug loading and circulation traits.

Light-driven rGO/Cu2 + 1O tubular nanomotor with active targeted drug delivery for combination treatment of cancer cells.

The unprecedented navigation ability in micro/nanoscale and tailored functionality tunes micro/nanomotors as new target drug delivery systems, open up new horizons for biomedical applications. Herein, we designed a light-driven rGO/Cu2 + 1O tubular nanomotor for active targeting of cancer cells as a drug delivery system. The propulsion performance is greatly enhanced in real cell media (5% glucose cells isotonic solution), attributing to the introduction of oxygen vacancy and reduced graphene oxide (rGO) layer for separating photo-induced electron-hole pairs. The motion speed and direction can be readily modulated. Meanwhile, doxorubicin (DOX) can be loaded quickly on the rGO layer because of π-π bonding effect. The Cu2 + 1O matrix in the tiny robots not only serves as a photocatalyst to generate a chemical concentration gradient as the driving force but also acts as a nanomedicine to kill cancer cells as well. The strong propulsion of light-driven rGO/Cu2 + 1O nanomotors coupled with tiny size endow them with active transmembrane transport, assisting DOX and Cu2 + 1O breaking through the barrier of the cell membrane. Compared with non-powered nanocarrier and free DOX, light-propelled rGO/Cu2 + 1O nanomotors exhibit greater transmembrane transport efficiency and significant therapeutic efficacy. This proof-of-concept nanomotor design presents an innovative approach against tumor, enlarging the list of biomedical applications of light-driven micro/nanomotors to the superficial tissue treatment.

Nanomedicine embraces cancer radio-immunotherapy: mechanism, design, recent advances, and clinical translation.

Cancer radio-immunotherapy, integrating external/internal radiation therapy with immuno-oncology treatments, emerges in the current management of cancer. A growing number of pre-clinical studies and clinical trials have recently validated the synergistic antitumor effect of radio-immunotherapy, far beyond the "abscopal effect", but it suffers from a low response rate and toxicity issues. To this end, nanomedicines with an optimized design have been introduced to improve cancer radio-immunotherapy. Specifically, these nanomedicines are elegantly prepared by incorporating tumor antigens, immuno- or radio-regulators, or biomarker-specific imaging agents into the corresponding optimized nanoformulations. Moreover, they contribute to inducing various biological effects, such as generating in situ vaccination, promoting immunogenic cell death, overcoming radiation resistance, reversing immunosuppression, as well as pre-stratifying patients and assessing therapeutic response or therapy-induced toxicity. Overall, this review aims to provide a comprehensive landscape of nanomedicine-assisted radio-immunotherapy. The underlying working principles and the corresponding design strategies for these nanomedicines are elaborated by following the concept of "from bench to clinic". Their state-of-the-art applications, concerns over their clinical translation, along with perspectives are covered.

Multifunctional Dendritic Au@SPP@DOX Nanoparticles Integrating Chemotherapy and Low-Dose Radiotherapy for Enhanced Anticancer Activity.

Combined chemoradiotherapy can improve antitumor efficiency and reduce the side effects of monotherapy. In this study, we aimed to construct dendritic peptide-based multifunctional nanoparticles (Au@SPP@DOX) for a prolonged circulation time, enhanced cellular uptake, and targeted cancer therapy. Amphiphilic micelle PEG-polylysine-SA (SPP) is composed of polylysine combined with hydrophilic poly(ethylene glycol) (PEG) and hydrophobic stearic acid (SA). Doxorubicin (DOX) is loaded via the hydrophilic-hydrophobic interaction of SPP, and gold nanoparticles (AuNPs) are loaded via the electrostatic interaction with SPP. Au@SPP@DOX showed good biocompatibility and could be successfully accumulated at tumor sites through the enhanced permeability and retention (EPR) effect. Then, lysosomes could be ruptured due to the proton sponge effect. DOX became protonated in response to tumor extracellular acidity and was then released from SPP. Under the action of low-dose radiation, Au@SPP@DOX could promote the production of reactive oxygen species (ROS), increase mitochondrial dysfunction, block cell division, and ultimately promote tumor cell apoptosis to achieve a better antitumor effect. This study highlighted the benefit of chemoradiotherapy and suggested that Au@SPP@DOX might serve as a high-efficiency codelivery system for cancer combination therapy in the future.

Investigating the Biodegradation Mechanism of Poly(trimethylene carbonate): Macrophage-Mediated Erosion by Secreting Lipase.

Poly(trimethylene carbonate) (PTMC), as one of the representatives of biodegradable aliphatic polycarbonates, has been found to degrade in vivo via surface erosion. This unique degradation behavior and the resulting nonacidic products make it more competitive with aliphatic polyesters (e.g., polylactide) in clinical practice. However, this surface degradation mechanism is complicated and not fully understood to date despite the findings that several reactive oxygen species and enzymes can specifically degrade PTMC in vitro. Herein, the biodegradation mechanism of PTMC was investigated by using possible degradation factors, distinct cell lines, and the inhibitors of these factors. The results demonstrate that PTMC undergoes a specific macrophage-mediated erosion. Macrophages tend to fuse into giant cells and elicit a typical inflammatory response by releasing proinflammatory cytokines. In addition, macrophages are suggested to primarily secrete enzymes (lipase specifically) to erode the PTMC bulk extracellularly as inhibiting their activity effectively prevented this eroding process. The clarification of the biodegradation mechanism in this work suggests that the degradation of PTMC highly depends on the foreign body response. Thus, it reminds the researchers to consider the effect of the microenvironment on the degradation and drug release of PTMC-based implantation devices and localized drug delivery systems.

Bimetallic-MOF-Derived Amorphous Zinc/Cobalt-Iron-Based Hollow Nanowall Arrays via Ion Exchange for Highly Efficient Oxygen Evolution.

Oxygen evolution reaction (OER) is critical for optimizing renewable energy systems, including metal-air batteries and water electrolysis. One major challenge for OER is to develop durable and cost-effective electrocatalysts with high catalytic performance. Herein, a controllable ion-exchange method to synthesize amorphous zinc/cobalt-iron hydroxide-based hollow nanowall arrays (A-Zn/Co-Fe HNAs) derived from bimetallic metal-organic frameworks (MOFs) on carbon cloth is reported. The amorphous characteristic enables the presented materials with more electrocatalytic sites and short diffusion paths for rapid access to the electrolyte, achieving efficient charge transfer for OER. The optimized nanostructure of A-Zn/Co-Fe HNAs via tuning the amount of iron sulfate in the reaction solution delivers a low overpotential of 226 mV to reach a current density of 10 mA cm-2 with a small Tafel slope of 37.81 mV dec-1 while exhibiting high durability at varied current densities over 80 h. The remarkable electrochemical performance can be attributed to the synergistic effect from chemical elements of Zn, Co-Fe, and a robust hollow structure. This simple method of fabricating bimetallic-MOF-derived amorphous Zn/Co-Fe HNAs on carbon cloth can be applied as a practical platform for other OER electrocatalysts.

An Amphiphilic PEGylated Peptide Dendron-Gemcitabine Prodrug-Based Nanoagent for Cancer Therapy.

An amphiphilic peptide dendrimer conjugated with gemcitabine (GEM), PEGylated dendron-Gly-Phe-Leu-Gly-GEM (PEGylated dendron-GFLG-GEM), is developed as a nano-prodrug for breast cancer therapy. The self-assembled behavior is observed under a transmission electron microscopy and dynamic light scattering. The negatively charged surface and hydrodynamic size of the amphiphilic nanosized prodrug supported that the prodrug can maintain the stability of GEM during circulation and accumulate in the tumor tissue. Drug release assays are conducted to monitor the release of GEM from this nanodrug delivery system in response to the tumor microenvironment, and these assays confirm that GEM released from the nanocarrier is identical to free GEM. The GEM prodrug can prevent proliferation of tumor cells. The therapeutic effect against breast cancer is systematically investigated using an in vivo animal model. Immunohistochemical results are aligned with the significantly enhanced anticancer efficacy of GEM released from the prodrug. This self-assembled amphiphilic drug delivery nanocarrier may broaden the application for GEM and other anticancer agents for breast cancer chemotherapy.

Dendron-Functionalized Polyglutamate-Pyropheophorbide-a Conjugates as Nanomedicines for Breast Cancer Photodynamic Therapy.

Photodynamic therapy (PDT) has shown its promise in the treatment of cancer. Herein, a dendron-functionalized polyglutamic acid (PGA) polymer (PG-L8G-Ppa-Dendron, PGPD) is synthesized and it is conjugated with pyropheophorbide-a (Ppa) for the first time to treat triple negative breast cancer (TNBC), whereas a linear polyglutamate-Ppa conjugate (PGP) is synthesized as a control. Compared to the linear counterpart, the glycosylated polymer-based PGPD with a dendritic structure has excellent solubility and it self-assembles to form uniform-sized nanoparticles. PGPD displays a highly effective PDT effect in the animal model, evidenced with effective induction of reactive oxygen species (ROS) production and cell apoptosis. This may be due to an enhanced efficiency in delivery and accumulation of Ppa by this glycosylated dendritic polymer at tumor sites. Therefore, PGPD can be a highly effective and biosafe nanoagent for PDT of TNBC.

A nitroxides-based macromolecular MRI contrast agent with an extraordinary longitudinal relaxivity for tumor imaging via clinical T1WI SE sequence.

BACKGROUND: Macromoleculization of nitroxides has been an effective strategy to improve low relaxivities and poor in vivo stability, however, nitroxides-based metal-free magnetic resonance imaging (MRI) macromolecular contrast agents (mCAs) are still under-performed. These mCAs do not possess a high nitroxides content sufficient for a cumulative effect. Amphiphilic nanostructures in these mCAs are not stable enough for highly efficient protection of nitroxides and do not have adequate molecular flexibility for full contact of the paramagnetic center with the peripheral water molecules. In addition, these mCAs still raise the concerns over biocompatibility and biodegradability due to the presence of macromolecules in these mCAs. RESULTS: Herein, a water-soluble biodegradable nitroxides-based mCA (Linear pDHPMA-mPEG-Ppa-PROXYL) was prepared via covalent conjugation of a nitroxides (2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl, PROXYL) onto an enzyme-sensitive linear di-block poly[N-(1, 3-dihydroxypropyl) methacrylamide] (pDHPMA). A high content of PROXYL up to 0.111 mmol/g in Linear pDHPMA-mPEG-Ppa-PROXYL was achieved and a stable nano-sized self-assembled aggregate in an aqueous environment (ca. 23 nm) was formed. Its longitudinal relaxivity (r1 = 0.93 mM- 1 s- 1) was the highest compared to reported nitroxides-based mCAs. The blood retention time of PROXYL from the prepared mCA in vivo was up to ca. 8 h and great accumulation of the mCA was realized in the tumor site due to its passive targeting ability to tumors. Thus, Linear pDHPMA-mPEG-Ppa-PROXYL could provide a clearly detectable MRI enhancement at the tumor site of mice via the T1WI SE sequence conventionally used in clinical Gd3+-based contrast agents, although it cannot be compared with DTPA-Gd in the longitudinal relaxivity and the continuous enhancement time at the tumor site of mice. Additionally, it was demonstrated to have great biosafety, hemocompatibility and biocompatibility. CONCLUSIONS: Therefore, Linear pDHPMA-mPEG-Ppa-PROXYL could be a potential candidate as a substitute of metal-based MRI CAs for clinical application.

Facile fabrication of multi-pocket nanoparticles with stepwise size transition for promoting deep penetration and tumor targeting.

BACKGROUND: Nanocarriers-derived antitumor therapeutics are often associated with issues of limited tumor penetration and dissatisfactory antitumor efficacies. Some multistage delivery systems have been constructed to address these issues, but they are often accompanied with complicated manufacture processes and undesirable biocompatibility, which hinder their further application in clinical practices. Herein, a novel dual-responsive multi-pocket nanoparticle was conveniently constructed through self-assembly and cross-linking of amphiphilic methoxypolyethylene glycol-lipoic acid (mPEG-LA) conjugates to enhance tumor penetration and antitumor efficacy. RESULTS: The multi-pocket nanoparticles (MPNs) had a relatively large size of ~ 170 nm at physiological pH which results in prolonged blood circulation and enhanced accumulation at the tumor site. But once extravasated into acidic tumor interstices, the increased solubility of PEG led to breakage of the supramolecular nanostructure and dissolution of MPNs to small-sized (< 20 nm) nanoparticles, promoting deep penetration and distribution in tumor tissues. Furthermore, MPNs exhibited not only an excellent stable nanostructure for antitumor doxorubicin (DOX) loading, but rapid dissociation of the nanostructure under an intracellular reductive environment. With the capacity of long blood circulation, deep tumor penetration and fast intracellular drug release, the DOX-loaded multi-pocket nanoparticles demonstrated superior antitumor activities against large 4T1 tumor (~ 250 mm3) bearing mice with reduced side effect. CONCLUSIONS: Our facile fabrication of multi-pocket nanoparticles provided a promising way in improving solid tumor penetration and achieving a great therapeutic efficacy.

Reactive Oxygen Species (ROS)-Degradable Polymeric Nanoplatform for Hypoxia-Targeted Gene Delivery: Unpacking DNA and Reducing Toxicity.

Smart polymers as ideal gene carriers have drawn increasing attentions due to the effective DNA release once triggered by intrinsic stimuli, as well as reduced cytotoxicity. Herein, a stimulus-responsive, positively charged and water-soluble polymer (OEI-TK x) was facilely engineered by cross-linking low molecular weight oligoethylenimine (OEI) via thioketal (TK) linkages that would cleave selectively in reactive oxygen species (ROS)-rich environments induced by hypoxia. Agarose gel electrophoresis assay demonstrated that the threshold N/P ratios for complete retardation of negatively charged DNA migration were above 5 for OEI-TK x. The reduction in DNA-condensing capability and the changes in particle size, size distribution and particle morphology all illustrated that OEI-TK x possessed excellent ROS responsiveness. OEI-TK x/DNA polyplexes showed lower toxicity and higher gene transfection efficiency compared with PEI/DNA polyplexes. The optimum formulation, OEI-TK x/DNA polyplexes (N/P = 40), showed a little better performance than PEI/DNA polyplexes in cellular uptake profile. Furthermore, OEI-TK x/DNA polyplexes could escape from endosomes to the cytosol as efficiently as PEI/DNA polyplexes. Confocal images confirmed that OEI-TK x/DNA polyplexes could more effectively release DNA than PEI/DNA polyplexes, mainly owing to the valid cleavage of thioketal linkages induced by characteristic rich-ROS in Hela cells. These results suggested that OEI-TK x could represent an on-demand stimulus-responsive gene delivery platform.

Covalent capture of supramolecular species in an aqueous solution of water-miscible small organic molecules.

Since an early report in the 1970s, the mesoscale inhomogeneities formed in an aqueous solution of water-miscible small organic molecules have been debated for over forty years with a variety of explanations. Although it was recently established that these inhomogeneities are supramolecular species caused by trace impurities, the structure of the supramolecular species and the mechanism behind their formation are not yet clear. By means of covalent capture, we herein disclose that the formation mechanism of the supramolecular species consists of a two-step self-assembly process: the small molecules first assemble into primary micelles with a trace amount of impurity, and the formed dynamic ultra-small micelles aggregate further through hydrogen bonding to achieve a buildup of thermodynamic mesoscale inhomogeneities. Based on this finding, supramolecular species have been used as elements for pH-responsive size-changeable drug carriers, which respond to the acidic tumour extracellular milieu and decompose into small particles for deep tumour penetration and effective distribution.

Electrochemical Deposition Tailors the Catalytic Performance of MnO2 -Based Micromotors.

Artificial micro/nanomotors that could perform diverse tasks autonomously at the micro/nanoscale have been emerging as promising tools in many practical applications. Electrochemical synthesis is one of the dominating methods to fabricate these micro/nanodevices with diverse geometries and material components. By changing the conditions of electrochemical deposition, the surface morphology, crystal structure, and hence the resultant performance of deposited material could be tailored. In the current work, a feasible fabrication strategy is presented in terms of three unique electrodeposition types (i.e., potentiodynamic, potentiostatic (PS), and galvanostatic) to synthesize different MnO2 -based micromotors. Distinct propulsion behavior as well as the catalytic degradation of azo-dye organic waste (with methylene blue as the representative), between three kinds of MnO2 -based micromotors is clearly displayed, owing to the distinctive chemical composition and morphology designs. The activated R-MnO2 -based micromotors in PS mode exhibit fast motion speed (up to 12 body length per second), leading to the highest degradation efficiency. Such propulsion performance is comparable with the microrockets made by noble metals such as Pt and Ag. The new protocol will have a profound impact on the design of synthetic micro/nanomotors and hold a considerable promise for their diverse applications.

Tailoring the Supramolecular Structure of Guanidinylated Pullulan toward Enhanced Genetic Photodynamic Therapy.

In the progress of designing a gene carrier system, what is urgently needed is a balance of excellent safety and satisfactory efficiency. Herein, a straightforward and versatile synthesis of a cationic guanidine-decorated dendronized pullulan (OGG3P) for efficient genetic photodynamic therapy was proposed. OGG3P was able to block the mobility of DNA from a weight ratio of 2. However, G3P lacking guanidine residues could not block DNA migration until at a weight ratio of 15, revealing guanidination could facilitate DNA condensation via specific guanidinium-phosphate interactions. A zeta potential plateau (∼+23 mV) of OGG3P complexes indicated the nonionic hydrophilic hydroxyl groups in pullulan might neutralize the excessive detrimental cationic charges. There was no obvious cytotoxicity and hemolysis, but also enhancement of transfection efficiency with regard to OGG3P in comparison with that of native G3P in Hela and HEK293T cells. More importantly, we found that the uptake efficiency in Hela cells between OGG3P and G3P complexes was not markedly different. However, guanidination caused changes in uptake pathway and led to macropinocytosis pathway, which may be a crucial reason for improved transfection efficiency. After introducing a therapeutic pKillerRed-mem plasmid, OGG3P complexes achieved significantly enhanced KillerRed protein expression and ROS production under irradiation. ROS-induced cancer cells proliferation suppression was also confirmed. This study highlights the guanidine-decorated dendronized pullulan could emerge as a reliable nonviral gene carrier to specifically deliver therapeutic genes.

Abnormal dynamic functional connectivity of amygdalar subregions in untreated patients with first-episode major depressive disorder.

BACKGROUND: Accumulating evidence supports the concept of the amygdala as a complex of structurally and functionally heterogeneous nuclei rather than as a single homogeneous structure. However, changes in resting-state functional connectivity in amygdalar subregions have not been investigated in major depressive disorder (MDD). Here, we explored whether amygdalar subregions - including the laterobasal, centromedial (CM) and superficial (SF) areas - exhibited distinct disruption patterns for different dynamic functional connectivity (dFC) properties, and whether these different properties were correlated with clinical information in patients with MDD. METHODS: Thirty untreated patients with first-episode MDD and 62 matched controls were included. We assessed between-group differences in the mean strength of dFC in each amygdalar subregion in the whole brain using general linear model analysis. RESULTS: The patients with MDD showed decreased strength in positive dFC between the left CM/SF and brainstem and between the left SF and left thalamus; they showed decreased strength in negative dFC between the left CM and right superior frontal gyrus (p < 0.05, family-wise error-corrected). We found significant positive correlations between age at onset and the mean positive strength of dFC in the left CM/brainstem in patients with MDD. LIMITATIONS: The definitions of amygdalar subregions were based on a cytoarchitectonic delineation, and the temporal resolution of the fMRI was slow (repetition time = 2 s). CONCLUSION: These findings confirm the distinct dynamic functional pathway of amygdalar subregions in MDD and suggest that the limbic-cortical-striato-pallido-thalamic circuitry plays a crucial role in the early stages of MDD.

Abnormal dynamic functional connectivity of amygdalar subregions in untreated patients with first-episode major depressive disorder.

BACKGROUND: Accumulating evidence supports the concept of the amygdala as a complex of structurally and functionally heterogeneous nuclei rather than as a single homogeneous structure. However, changes in resting-state functional connectivity in amygdalar subregions have not been investigated in major depressive disorder (MDD). Here, we explored whether amygdalar subregions - including the laterobasal, centromedial (CM) and superficial (SF) areas - exhibited distinct disruption patterns for different dynamic functional connectivity (dFC) properties, and whether these different properties were correlated with clinical information in patients with MDD. METHODS: Thirty untreated patients with first-episode MDD and 62 matched controls were included. We assessed between-group differences in the mean strength of dFC in each amygdalar subregion in the whole brain using general linear model analysis. RESULTS: The patients with MDD showed decreased strength in positive dFC between the left CM/SF and brainstem and between the left SF and left thalamus; they showed decreased strength in negative dFC between the left CM and right superior frontal gyrus (p < 0.05, family-wise error-corrected). We found significant positive correlations between age at onset and the mean positive strength of dFC in the left CM/brainstem in patients with MDD. LIMITATIONS: The definitions of amygdalar subregions were based on a cytoarchitectonic delineation, and the temporal resolution of the fMRI was slow (repetition time = 2 s). CONCLUSION: These findings confirm the distinct dynamic functional pathway of amygdalar subregions in MDD and suggest that the limbic-cortical-striato-pallido-thalamic circuitry plays a crucial role in the early stages of MDD.

Polyethylene Glycol-Functionalized Magnetic Fe3O4/P(MMA-AA) Composite Nanoparticles Enhancing Efficient Capture of Circulating Tumor Cells.

Circulating tumor cells (CTCs) played a significant role in early diagnosis and prognosis of carcinomas, and efficient capture of CTCs was highly desired to provide important and reliable evidence for clinical diagnosis. In present work, we successfully synthesized functional magnetic Fe3O4/P(MMA-AA) composite nanoparticles (FCNPs) inspired by a counterbalance concept for recognition and capture of CTCs. This counterbalance, composed of polyethylene glycol (PEG) suppressing cell adhesion and anti-epithelial-cell-adhesion-molecule (anti-EpCAM) antibody targeting tumor cells, could both enhance the specific capture of tumor cells and reduce unspecific adhesion of normal cells. The study showed that the PEG density on the surface of the FCNPs affected the specificity of the materials, and a density of ca. 15% was efficient for reducing the unspecific adhesion. After incubation with the mixture of HepG2 cells and Jurkat T cells, the FCNPs reached a capture efficiency as high as about 86.5% of the cancer cells, suggesting great potential on detection of CTCs in the diagnoses and prognoses of cancer metastasis.

Confined Pool-Buried Water-Soluble Nanoparticles from Reverse Micelles.

With the special nature of confined water pools, reverse micelles (RMs) have shown potential for a wide range of applications. However, the inherent water insolubility of RMs hinders their further application prospect especially for applications related to biology. We present herein the first successful transformation of water-insoluble RMs into water-soluble nanoparticles without changing the confined aqueous interiors by hydrolysis/aminolysis of arm-cleavable interfacial cross-linked reverse micelles formed from diester surfactant 1. The unique properties exhibited by the aqueous interiors of the resulting pool-buried water-soluble nanoparticles (PWNPs) were demonstrated both by the template synthesis of gold nanoparticles in the absence of external reductants and by the fluorescence enhancement of encapsulated thioflavin T (ThT). Importantly, the unique potential for PWNPs in biological applications was exemplified by the use of ThT@PWNPs and "cell targeted" ThT@PWNPs as effective optical imaging agents of living cells. This work conceptually overcomes the application bottleneck of RMs and opens an entry to a new class of functional materials.

Terminal Acetylated/Acrylated Poly(ethylene glycol) Fabricated Drug Carriers: Design, Synthesis, and Biological Evaluation.

The simple acetylation or acrylation of poly(ethylene glycol) (PEG) terminus leads to the aggregation of PEG chains into spherical nanoparticles in water at room temperature and very low concentrations. The experiment results suggest that this aggregation happens by the variation of the local conformation of the O-CH2-CH2-O segments of PEG chains caused by the introduced acyl group, which disturbs the originally strict hydrogen bond mode between the O-CH2-CH2-O groups and the water molecules. The simple modified PEG nanoparticles are excellent carriers for drug delivery. As examples, the cross-linkable 1d-based drug delivery systems, cPEG@SN-38 and targeted cPEG@SN-38, are successfully established by their high drug loading content (18 wt %/wt) and enhanced anticancer efficacy both in vitro and in vivo while obviating the inherent toxicity of the employed chemotherapeutics. This strategy that revolves around the simple modification of the generally regarded as safe (GRAS) modules to fabricate drug carriers represents a new direction for the drug delivery systems with clinical potential.