Anti-ROS and NIR-II-Responsive Hyaluronic Acid Microneedle Loaded With Baicalin Nanoparticles for Treatment of Psoriasis.

In this work, a natural medicine, baicalin, is designed for the treatment of psoriasis with the aid of hyaluronic acid (HA)-based MNs patches. This is also to improve the solubility of baicalin and increase its residence time in infected part, which is made into nanoparticles by complexation with humic acid and Eu2+. The baicalin nanoparticles loaded-MNs exhibit satisfactory rigidity, minimum injury, and controlled drug delivery. The anti-reactive oxygen species (anti-ROS) and anti-inflammatory action are verified by the effective scavenging oxygen and nitrogen radicals. In addition, the loading of baicalin nanoparticles brings remarkable photothermic effect to the MNs, enabling the device to release a controlled drug under near-infrared region II (NIR-II) laser irradiation. With the aid of NIR-II laser, the baicalin-mediated treatment of psoriasis is significantly improved by expediting radical scavenging and suppressing inflammation. The design of baicalin MNs provides a new idea for the treatment of chronic disease.

Comparison of Sericins from Different Sources as Natural Therapeutics against Ulcerative Colitis.

Sericin has become a promising natural anti-inflammatory protein. However, the biological functions of sericins largely depend on their origins; no study has yet been carried out to comparatively investigate the therapeutic effects of sericins from different sources against inflammatory diseases. Herein, we extracted and purified three kinds of sericins, namely silkworm sericin (SS), tussah sericin (TS), and castor silk sericin (CSS). These sericins showed negligible cytotoxicities against colitis-associated cells (colon epitheliums and activated macrophages). Further investigations displayed that these sericins could remarkably downregulate the secreted amounts of TNF-α, promote the recovery of the damaged colonic epithelial barrier, and eliminate endogenous reactive oxygen species in Raw 264.7 macrophages and Caenorhabditis elegans. In vivo experiments demonstrated that chitosan/alginate hydrogel-encapsulating SS could achieve efficient accumulation of SS in the colitis tissues and thereby play a more effective role in relieving ulcerative colitis (UC) than TS and CSS. Our findings collectively demonstrate that SS can be extracted, formulated, and used as a robust therapeutic agent for the oral treatment of UC.

Synergistically boosting the electrochemical performance of polypyrrole-coated activated carbon derived from carbon dots for a high-performance supercapacitor.

Hybrid materials were prepared via the controlled fumigation-based polymerization of pyrrole on the surface of activated carbon derived from carbon dots, combining the stability of carbon materials, the wettability of carbon dots, and the high pseudocapacitance of polypyrrole; all of these synergistically boosted the electrochemical performance, resulting in a high specific capacitance (481 F g-1) and good stability for supercapacitor applications.

Engineering silk sericin decorated zeolitic imidazolate framework-8 nanoplatform to enhance chemotherapy.

The low therapeutic effect and strong side-effect are the major barriers for clinical chemotherapy. Herein, a pH-responsive nanoplatform based-silk sericin-zeolitic imidazolate framework-8 was designed for the delivery of chemotherapeutic doxorubicin (denoted as ZIF-8@DOX@SS, ZDS), which can overcome the limitation of poor circulation stability and unexpected drug leakage in blood circulation, producing a satisfactory chemotherapy. Concretely, ZIF-8 structure shows better stability and biocompatibility owing to the protection of a nature and non-toxic sericin protein. When it comes to low pH environment (e.g. in tumor cell microenvironment), the coordination effect in ZIF-8 will be broken and release DOX drugs. The nano-sized morphology endow ZDS an efficient drug uptake and significant tumor permeability efficiency. Furthermore, the tumor-specific biodegradability makes ZDS possible to realize targeted and enhanced chemotherapy. Considering all the advantages in the study, this silk sericin-based nanosystem represent a promising strategy for the design of stimuli-responsive by using natural polymer to improve the treatment effect of chemotherapy.

Orange red-emitting carbon dots for enhanced colorimetric detection of Fe3.

Carbon dots (CDs) have demonstrated considerable potential for use in sensing and bioimaging applications based on their unique intrinsic properties. However, CDs have typically been used as fluorescence sensors, as opposed to indicators, based on their ultraviolet absorption and discoloration performance. In this study, orange red-emitting CDs with a high quantum yield (QY) of 53% were constructed from 2,3-diaminopyridine via solvothermal synthesis. Different from the fluorescence quenching behavior reported previously, the constructed CDs demonstrated a unique character in their ultraviolet absorption and fluorescence emission in the presence of Fe3+. The color of the CD solution varied from mauve to orange following the addition of Fe3+ at concentrations exceeding 1 µM, which enabled these CDs to be used in the determination of the presence of Fe3+ in lake water. In addition, due to their negligible cytotoxicity, good solubility, and adequate dispersity, an outstanding cellular probe with near-infrared fluorescence was established. Overall, this study presents a unique CD-based sensor, details its fluorescence mechanism, visual colorimetry, and ultraviolet absorption variations, and confirms its applicability in near-infrared cellular imaging and environmental analyses.

The design and synthesis of dextran-doxorubicin prodrug-based pH-sensitive drug delivery system for improving chemotherapy efficacy.

Tumor cells show acidic conditions compared with normal cells, which further inspires scientist to build nanocarrier responsive to tumor microenvironment (TME) for enhancing tumor therapeutic efficacy. Here, we report a pH-sensitive and biocompatible polyprodrug based on dextran-doxorubicin (DOX) prodrug (DOXDT) for enhanced chemotherapy. High-density DOX component was covalently decorated on the nanocarrier and the drug molecules could be effectively released in the acidic tumor tissue/cells, improving chemotherapy efficacy. Specifically, a dextran-based copolymer was preliminarily prepared by one-step atom transfer radical polymerization (ATRP); then DOX was conjugated on the copolymer component via pH-responsive hydrazone bond. The structure of DOXDT can be well-controlled. The resulting DOXDT was able to further self-assemble into nanoscale micelles with a hydration diameter of about 32.4 nm, which presented excellent micellar stability. Compared to lipid-based drug delivery system, the DOXDT prodrug showed higher drug load capacity up to 23.6%. In addition, excellent stability and smaller size of the nanocarrier contributed to better tissue permeability and tumor suppressive effects in vivo. Hence, this amphipathic DOXDT prodrug is promising in the development of translational DOX formulations, which would be widely applied in cancer therapy.

Indole Carbonized Polymer Dots Boost Full-Color Emission by Regulating Surface State.

Carbonized polymer dots (CPDs) are impressive imaging probes with great potential for enriching the library of metal-free fluorescent materials, yet current strategies have struggled to achieve products that emit full-color light in a single reaction system. Establishing an efficient and robust synthesis approach that unlocks the color barrier to the luminescence centers of specific CPDs remains a challenge. Herein, the surface-state engineering of pyridine and amide in the indole system to create a palette of resolvable full-color light-emissive CPDs is reported. Detailed structural analysis revealed that cationic polymerization and oxidation reactions potentially contribute to the formation of the main frameworks and emission centers of the final CPDs, with emissive oxygen- and nitrogen-based centers fixed by cross-linked polymer structures. This study provides valuable insight into the energy absorbance and photoluminescence mechanism of CPDs and introduces additional reactants (benzo heterocycle) into CPD research.

One-step microwave synthesis of N,S co-doped carbon dots from 1,6-hexanediamine dihydrochloride for cell imaging and ion detection.

As a new member of the fluorescent carbon nanomaterial family, carbon dots (CDs) not only have outstanding photoluminescence properties and small size characteristics, but also contain favourable low cytotoxicity and biocompatibility, which could be the best choice to detect of ions to replace quantum dots for ions detection. Here, the N,S co-doped carbon dots (N/S-CDs) was synthesized by one-step microwave using 1,6-hexanediamine dihydrochloride and dimethyl sulfoxide as precursors, and their morphology and structure were characterized by TEM, XRD, XPS and FTIR. The optimal emission wavelength of the CDs was 512 nm with green fluorescence, and was red-shifted gradually as the excitation wavelength aggrandized. The synthesized CDs owned a well quantum yield of 24 %. It was further applied for the detection of MnO4- and Cr2O72- with an excellent detection limit of 0.34 µM and 0.23µM, respectively. Cr2O72- did not influence the N/S-CDs PL response of MnO4- in the presence of excessive Pb2+. Moreover, the obtained N/S-CDs demonstrated preeminent biocompatibility and could be resoundingly applied for cellular imaging.

Codelivery of doxorubicin and camptothecin by dual-responsive unimolecular micelle-based ß-cyclodextrin for enhanced chemotherapy.

Tumor microenvironment (TME)-induced drug delivery technology is a promising strategy for improving low drug accumulation efficiency, short blood circulation and weak therapeutic effect. In this work, a dual-responsive (reduction- and pH-responsive) polyprodrug nanoreactor based on ß-cyclodextrin (ß-CD) was constructed for combinational chemotherapy. Specifically, the dual-responsive star polymeric prodrug was synthesized by atom transfer radical polymerization (ATRP) based on a starburst initiator of ß-CD-Br. The obtained polyprodrug contained a hydrophilic chain of poly-(ethylene glycol) methyl ether methacrylate (POEGMA) and a hydrophobic part of camptothecin (CPT) prodrug and poly[2-(diisopropylamino)ethyl methacrylate] (PDPA), denoted as ß-CD-PDPA-POEGMA-PCPT (CCDO for short). The obtained CCDO could form stable unimolecular micelles, which could be efficiently internalized by cancer cells. To enhance the curative effect, the anticancer agent doxorubicin (DOX) could be encapsulated into the hydrophobic cavity of the CCDO by hydrophobic-hydrophobic interaction. In vitro drug release studies showed that the obtained CCDO/DOX micelles controlled the release of active CPT and DOX occurring in a reductive environment and at low pH. In vitro cytotoxicity results suggested that the anticancer efficacy of dual-responsive CCDO/DOX micelles was superior to that of CCDO micelles. In addition, in vivo results verified good blood compatibility of the unimolecular micelles. This integrated dual-responsive drug delivery system may solve the low drug loading and poor controlled release problems found in traditional polymer-based drug carriers, providing an innovative and promising route for cancer therapy.

High quantum yield blue- and orange-emitting carbon dots: one-step microwave synthesis and applications as fluorescent films and in fingerprint and cellular imaging.

A high quantum yield (QY) is the key requirement for implementing carbon dots (CDs) in nearly all applications. In this work, blue emissive N-doped CDs with a QY of 83% and orange emissive N-doped CDs with a QY of 47% were successfully prepared using resorcinol and phloroglucin as carbon resources in formamide by one-step microwave synthesis, respectively. Formamide not only plays a role as the solvent but also takes part in the formation of the high QY CDs. It is demonstrated that the as-prepared blue- and orange-emitting N-doped CDs with a high QY can be uniformly dispersed into glue and be fabricated as CD/glue fluorescent composites for fluorescent films and fingerprint imaging. Furthermore, these CDs also show excellent cellular imaging capability.

Modulation of drug release by decoration with Pluronic F127 to improve anti-colon cancer activity of electrospun fibrous meshes.

Applications of fibrous meshes for localized chemotherapy have been limited by the lack of optimal carriers that are capable of releasing sufficient drug locally. To overcome this obstacle, we introduced Pluronic F127 (PF127) to the camptothecin (CPT)-loaded poly(lactic acid/glycolic acid) (PLGA) electrospun fibrous meshes, abbreviated as PPC, for modulation of drug release. These PPC meshes had smooth surface and high drug loading (5.6-6.8%). Addition of PF127 obviously improved the hydrophilicity of the meshes. Interestingly, the CPT release rate of PPC meshes was significantly higher than that of CPT-loaded PLGA (PLGA-CPT) meshes. Most importantly, incorporation of PF127 in the meshes led to significant reduction in the CT-26 viability compared to PLGA-CPT mesh. The improved anticancer effects of PPC meshes were mainly due to the induction of apoptosis in CT-26 cells. These findings suggest that PPC mesh could be a promising implantable system that may enhance the therapeutic efficacy and prevent tumor recurrence after surgical resection.

Nanostructured MXene-based biomimetic enzymes for amperometric detection of superoxide anions from HepG2 cells.

A novel MXene-based biomimetic enzyme was synthesized using adenosine triphosphate (ATP) as a template to modify a Mn3(PO4)2 nanostructure on Mxene-Ti3C2 nanosheets. The resulting composite was used as an electrode material in an electrochemical sensor for superoxide anion (O2•-). It displays excellent catalytic properties which is attributed to the synergistic effects of the two-dimensional conductive substrate and the Mn3(PO4)2 nanoparticles. The addition of ATP results in the formation of a porous and ordered nanostructure of Mn3(PO4)2. This facilitates the electron transfer between O2•- and electrode. The sensor, best operated at 0.75 V (vs. Ag/AgCl), displays a rapid amperometric response with a detection limit of 0.5 nM and an analytical range that extends from 2.5 nM to 14 µM. Conceivably, it has potential in the detection of O2•- released by living cells. Graphical abstract Nanostructured MXenes were synthesized by in-situ growth of Mn3(PO4)2 on Ti3C2 nanosheets under the induction of adenosine triphosphate (ATP). They display enzyme mimickong properties. A sensor fabricated with the composites can be used for the detection of superoxide anions released by HepG2 cells.

Oral Administration of Hydrogel-Embedding Silk Sericin Alleviates Ulcerative Colitis through Wound Healing, Anti-Inflammation, and Anti-Oxidation.

Silk sericin (SS) is abundant in silk industry wastewater, and it has emerged as a promising natural protein for biomedical research. However, its therapeutic potential against ulcerative colitis (UC) has not been exploited. The objective of this study is to investigate the therapeutic effects of SS in a dextran sulfate sodium-induced UC mouse model, and further discover its underlying mechanisms. The purified SS molecules showed negative cytotoxicity, and could be efficiently internalized by colonic epithelial cells and macrophages. In vitro experiments revealed that it could accelerate the mucosal healing, down-regulate the production of pro-inflammatory factors, increase the secretion of anti-inflammatory cytokines, and eliminate the intracellular reactive oxygen species. Finally, animal experiments confirmed that oral administration of hydrogel (chitosan/alginate)-embedding SS molecules attenuated UC-induced symptoms (e.g., body weight loss, colon shortening, increase of spleen weight, and histopathological appearance), which was supported by signs of mucosal healing, anti-inflammation, and elevation of the amounts of tight junction proteins (occludin and zonula occludens-1) and mucin protein (MUC2). Taken together, our results demonstrate that SS can be exploited as a promising oral natural therapeutic for UC treatment with the aid of hydrogel.

Facile Fabrication of Oxidation-Responsive Polymeric Nanoparticles for Effective Anticancer Drug Delivery.

Reactive oxygen species (ROS) are highly overproduced in cancerous tissues, and thus oxidation-responsive nanoparticles (NPs) have emerged as a promising drug carrier for cancer-targeted drug delivery. In this study, we successfully synthesized poly(vanillyl alcohol- co-oxalate) (PVAX) polymer with an excellent ROS-responsive capacity. A well-established emulsion-solvent evaporation method was used to fabricate PVAX-based curcumin (CUR)-loaded NPs (PVAX-NPs) and their counterparts (poly(lactic- co-glycolic acid)-based CUR-loaded NPs, PLGA-NPs). It was found that these NPs had a hydrodynamic particle size of approximately 245 nm, narrow size distribution (polydispersity index less than 0.1), negative zeta potential (around -18 mV), smooth surface appearance, and high drug encapsulation efficiency. Moreover, we found that the CUR release rate of PVAX-NPs was greatly increased in the presence of a hydrogen peroxide-rich environment due to the cleavage of polyoxalate ester bonds in PVAX polymer, resulting in the evenly distribution of CUR within the whole cancer cells. More importantly, PVAX-NPs exhibited much stronger anticancer activities and pro-apoptotic capacities than PLGA-NPs both in vitro and in vivo. These results clearly demonstrate that these ROS-responsive PVAX-NPs can be exploited as a robust anticancer drug delivery platform in chemotherapy.

Orange, yellow and blue luminescent carbon dots controlled by surface state for multicolor cellular imaging, light emission and illumination.

Three kinds of carbon dots (CDs) with different photoluminescence (PL) (blue, yellow or orange) were synthesized by microwave heating. They display wavelength-independent excitation wavelengths (in the range from 444 to 574 nm), similar average particle size (from 3.7 to 4.2 nm), and fluorescence lifetimes (from 2.7 to 3.1 ns). Color and quantum yields (from 8 to 45% in ethanol) are related to the oxidation degree and the number of N-functional groups on their surface. The CDs are shown to be viable nanoprobes for multicolor imaging of cells. Three composite phosphors were obtained by coating the various CDs on starch particle. The resulting nanomaterials emit solid-state fluorescence with a quantum yield of ≥16%. They were used to fabricate luminescent blocks and light-emitting diodes with controllable color temperature. Graphical abstract (a) The synthesis process of the three carbon dots (CDs). The application in cell imaging (b), starch/CD phosphors (c), starch/CD phosphors-based luminescent blocks (d) and light-emitting diodes (e). (λex: excitation wavelength).

Acid-active supramolecular anticancer nanoparticles based on cyclodextrin polyrotaxanes damaging both mitochondria and nuclei of tumor cells.

As a supramolecular macrocyclic polymer, cyclodextrin (CD) polyrotaxanes (PRs) have many advantages for developing nanomedicines, such as stable chemical composition, abundant functionalized hydroxyl groups, moving across biological barriers, adjustable nanoparticle size and good biocompatibility. Herein, we synthesized a class of acid-active therapeutic nanoparticles comprising a α-CD-based PR polymeric prodrug of PRs-poly(doxorubicin)-co-poly[(ethylene glycol) methyl ether methacrylate] (PR-PDOX-co-POEGMA, denoted as PRMO@DOX) to reduce drug leakage and selectively deliver drugs into tumor cells, aiming to achieve maximal treatment efficacy of supramolecular therapeutics. The obtained PRMO@DOX showed desirable features of high drug loading rates (>25 wt%), fast cellular uptake, acid-active controlled release, effective anti-tumor activity and low systemic toxicity. Benefiting from its unique amphiphilic nanostructure, PRMO@DOX can form water-soluble prodrug nanoparticles in aqueous media. The acid-active hydrazone bond in the prodrug can break and thus release drug molecules precisely and in a timely manner under an acidic tumor microenvironment, damaging the nuclei and mitochondria of tumor cells. Both in vitro and in vivo experiments clearly demonstrated a remarkable antitumor efficacy of this therapeutic platform, which provided a new strategy for the development of polyrotaxane-based nanomedicine for enhanced cancer therapy.

A Label-Free Aptasensor for Ochratoxin a Detection Based on the Structure Switch of Aptamer.

A label-free sensing platform is developed based on switching the structure of aptamer for highly sensitive and selective fluorescence detection of ochratoxin A (OTA). OTA induces the structure of aptamer, transforms into G-quadruplex and produces strong fluorescence in the presence of zinc(II)-protoporphyrin IX probe due to the specific bind to G-quadruplex. The simple method exhibits high sensitivity towards OTA with a detection limit of 0.03 nM and excellent selectivity over other mycotoxins. In addition, the successful detection of OTA in real samples represents a promising application in food safety.

Reduction-active polymeric prodrug micelles based on α-cyclodextrin polyrotaxanes for triggered drug release and enhanced cancer therapy.

As one of the medical polymers approved by US Food and Drug Administration (FDA), poly(ethylene glycol) has low toxicity, high stability, good biocompatibility, unique physical and chemical properties. Cyclodextrin is an ideal candidate as a drug carrier due to its special structures and characteristics. These two materials were successfully assembled through chemosynthesis in combination with the hydrophilic poly(ethylene glycol) methyl ether methacrylate (OEGMA) chain and hydrophobic polymeric camptothecin (CPT) chain by atom transfer radical polymerization (ATRP). The introduction of disulfide bond of monomer was aimed to realize reduction agent-triggered release of active CPT. The obtained amphipathic prodrug [(Denoted as PC-PCPT-b-POEGMA (PCCO)] could form nano-sized polymeric micelles, which could release more than 85% of the loaded CPT via triggered cleavage of the disulfide linker. The cellular co-localization study revealed the potential pathway of drug internalization. Moreover, the PCCO micelles showed good biocompatibility in vivo after intravenous injection on a mouse model. This new CPT-loaded prodrug system could be prepared with low cost, and showed efficient and controlled drug release and favorable biocompatibility, demonstrating a promising potential as a stimuli-responsive polymeric prodrug for future clinical applications.

Improving the carrier stability and drug loading of unimolecular micelle-based nanotherapeutics for acid-activated drug delivery and enhanced antitumor therapy.

Nanomedicines based on unimolecular micelles (UMs) have shown unique advantages such as high micellar stability, programmed cargo delivery and enhanced therapeutic efficiency. Herein, we report an acid-activated amphiphilic prodrug based on a dextran (DEX) polymeric framework (DEX-PDOX-b-POEGMA, labelled DMO@DOX), which conjugates a diblock copolymer of a hydrophobic doxorubicin (DOX) prodrug block and a hydrophilic poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) block by atom transfer radical polymerization. The DMO@DOX prodrug can form nano-sized UMs in aqueous media attributed to its amphiphilic structure and achieve a very high drug loading rate of 80.4 wt%. In the presence of an acidic medium resembling a tumor microenvironment, the hydrazone bond embedded in the prodrug is broken, which releases the loaded drug of DOX. The DMO@DOX prodrug shows a notable and preferential inhibition effect on the growth of tumor cells in vitro compared to healthy cells, leading to advantageous biocompatibility and effective antitumor activity. For verification, the DMO@DOX prodrug was applied in the treatment of a mouse model bearing xenograft tumors and showed a remarkable therapeutic performance. This study demonstrates an effective design of UM-based nanoagents to improve the micellar stability of polymeric prodrug micelles with enhanced performance in cancer therapy.

DNA-induced synthesis of biomimetic enzyme for sensitive detection of superoxide anions released from live cell.

In this work, we successfully fabricate a rapid, sensitive sensor for the detection of superoxide anions O2˙- based on graphene/DNA/Mn3(PO4)2 biomimetic enzyme. In the design, graphene is served as excellent carrier to improve the catalysis of Mn3(PO4)2 nanoparticles; and DNA adsorbed on graphene acts as medium to assist the growth of Mn3(PO4)2 on graphene. The fabricated graphene/DNA/Mn3(PO4)2 composites exhibit excellently electrochemical activity, significantly decrease the response time and increase the sensitivity of the sensor towards O2˙-. The successful detection of O2˙- released from cancer cell demonstrated its potential applications in biology and medicine.