Penthorum chinense Pursh leaf tea debittering mechanisms via green tea manufacturing process and its influence on NAFLD-alleviation activities.

The green-tea manufacturing process showed good effect of flavor improving, debittering and shaping in making Penthorum chinensePursh leaf (PL) tea (PLT), which serves as a polyphenol dietary supplement and beverage raw material. GC-MS results showed that its unpleasant grassy odor decreased by 42.8% due to dodecanal, geranylacetone, and (E)-2-nonenal reduction, coupled with 1-hexadecanol increasing. UPLC-ESI-TOF-MS identified 95 compounds and showed that the debittering effect of green-tea manufacturing process was attributed to decreasing of flavonols and lignans, especially quercetins, kaempferols and luteolins, and increasing of dihydrochalcones which act as sweeteners bitterness-masking agents, while astringency was weakened by reducing delphinidin-3,5-O-diglucoside chloride, kaempferol-7-O-ß-d-glucopyranoside, and tannins. The increase of pinocembrins and catechins in aqueous extracts of PLT, maintained its hepatoprotective, NAFLD-alleviation, and hepatofibrosis-prevention activities similar to PL in high fat-diet C57BL/6 mice, with flavonoids, tannins, tannic acids, and some newfound chemicals, including norbergenin, gomisin K2, pseudolaric acid B, tanshinol B, as functional ingredients.

Injectable thermosensitive black phosphorus nanosheet- and doxorubicin-loaded hydrogel for synergistic bone tumor photothermal-chemotherapy and osteogenesis enhancement.

Removing residual tumor cells around bone tissue and promoting bone defect repair pose significant challenges after osteosarcoma resection. Herein, we designed an injectable multifunctional hydrogel therapeutic platform for synergistic photothermal chemotherapy of tumors and promoting osteogenesis. In this study, the black phosphorus nanosheets (BPNS) and doxorubicin (DOX) were encapsulated in an injectable chitosan-based hydrogel (BP/DOX/CS). The BP/DOX/CS hydrogel exhibited excellent photothermal effects under NIR irradiation due to incorporating BPNS. The prepared hydrogel has good drug-loading capacity and can continuously release DOX. In addition, K7M2-WT tumor cells are effectively eliminated under the combined effect of chemotherapy and photothermal stimulation. Furthermore, the BP/DOX/CS hydrogel has good biocompatibility and promotes osteogenic differentiation of MC3T3-E1 cells by releasing phosphate. In vivo results also confirmed that the BP/DOX/CS hydrogel can be injected at the tumor site to eliminate the tumor efficiently without systemic toxicity. This easily prepared multifunctional hydrogel with a synergistic photothermal-chemotherapy effect has excellent potential for clinically treating bone-related tumors.

Janus-like Bx C/C Quantum Sheets with Z-Scheme Mechanism Strengthen Tumor Photothermal-Immunotherapy in NIR-II Biowindow.

Carbon dots (CDs) are one of the most popular photothermal agents (PTAs) as a noninvasive strategy for tumor treatment. However, because of the inherent dominant fluorescent emission, the CDs-based PTAs hardly achieve a single photothermal conversion, which causes low photothermal conversion efficiency and poor photothermal performance. In this regard, finding a new CDs-based material system to greatly restrain its fluorescence to enhance its photothermal conversion efficiency is highly required, however, it is still a grand challenge. Herein, a kind of Z-scheme CDs-based PTAs consisting of 2D ultrathin nonmetallic Bx C/C Janus quantum sheets (Bx C/C JQSs) is reported to greatly enhance the photothermal conversion efficiency. It is demonstrated that the heterogeneous growth of Z-scheme Bx C/C JQSs enables the NIR-driven quick injection of hot electrons from C into the conjugated Bx C, realizing a single conversion of light to heat, and resulting in a high photothermal conversion of 60.0% in NIR-II. Furthermore, these new Z-scheme Bx C/C-polyethylene glycol JQSs display outstanding biocompatibility and show effective tumor elimination outcome both in vitro and in vivo through the synergistic photothermal-immunotherapy in the NIR-II biowindow with undetectable harm to normal tissues.

Tumor-self-targeted "thermoferroptosis-sensitization" magnetic nanodroplets for multimodal imaging-guided tumor-specific therapy.

Ferroptosis-based nanomedicine has drawn increasing attention in antitumor therapy because of the advantages of this unconventional mode of apoptosis, but the difficulties of delivery to the tumor site and surface-to-core penetration after arrival seriously hinder further clinical transformation and application. Herein, we propose an unprecedented strategy of injecting magnetic nanodroplets (MNDs) to solve these two longstanding problems. MNDs are nanocarriers that can carry multifunctional drugs and imaging materials. MNDs can effectively accumulate in the tumor site by active tumor targeting (multifunctional drugs) and passive tumor targeting (enhanced permeability and retention effect), allowing diffusion of the MNDs from the surface to the core through mild-temperature magnetic fluid hyperthermia (MHT) under multimodal imaging guidance. Finally, the ferroptosis pathway is activated deep within the tumor site through the drug release. This approach was inspired by the ability of mild-temperature MHT to allow MNDs to quickly pass through the blood vessel-tumor barrier and deeply penetrate the tumor tissue from the surface to the core to amplify the antitumor efficacy of ferroptosis. This strategy is termed as "thermoferroptosis sensitization". Importantly, this behavior can be performed under the guidance of multimodal imaging, making the design of MNDs for cancer therapy safer and more reasonable.

Premna microphylla Turcz leaf pectin exhibited antioxidant and anti-inflammatory activities in LPS-stimulated RAW 264.7 macrophages.

Premna microphylla turcz leaf juice with polysaccharides (PMPs) as its main component, are raw material of jelly-like Chinese traditional food "Guanyin tofu", which were also experiencedly used to relieve inflammation-related symptoms. Here three kinds of PMPs were extracted in alkaline (APMP), water (WPMP) and acidic (HPMP) conditions, being characteristic of RG I, high- and low-methoxyl HG pectin, respectively, in amorphous form with diverse surface microstructures, among which APMP predominantly composed of Glucose instead of galacturonic acid, showing wider molecular weight distribution and more branched chains. PMPs showed remarkable radical scavenging capability, and especially APMP at concentrations above 50 µg/mL effectively inhibited the reactive oxygen species and malondialdehyde production in LPS-stimulated RAW 264.7 macrophages, by enhancing enzymatic activities of endogenous superoxide dismutase, glutathione peroxidase and catalase, and accordingly alleviated inflammatory cytokines. Thus, PMPs could be promising non-toxic natural dietary supplement to improve chronic inflammation-induced diseases.

Advanced Black Phosphorus Nanomaterials for Bone Regeneration.

Bone regeneration remains a great clinical challenge. Two-dimensional materials, especially graphene and its derivative graphene oxide, have been widely used for bone regeneration. Since its discovery in 2014, black phosphorus (BP) nanomaterials including BP nanosheets and BP quantum dots have attracted considerable scientific attention and are considered as prospective graphene substitutes. BP nanomaterials exhibit numerous advantages such as excellent optical and mechanical properties, electrical conductivity, excellent biocompatibility, and good biodegradation, all of which make them particularly attractive in biomedicine. In this review, we comprehensively summarize recent advances of BP-based nanomaterials in bone regeneration. The advantages are reviewed, the different synthesis methods of BP are summarized, and the applications to promote bone regeneration are highlighted. Finally, the existing challenges and perspectives of BP in bone regeneration are briefly discussed.

Integration of cascade delivery and tumor hypoxia modulating capacities in core-releasable satellite nanovehicles to enhance tumor chemotherapy.

Drug nanovehicles owning tumor microenvironment responsive and modulating capacities are highly demanding for effective tumor chemotherapy but still lack of exploration. Here, a kind of core-releasable satellite nanovehicles was rational constructed, which is composed of polydopamine (PDA) cores as photothermal agents and the carrier for small satellite nanoparticles (NPs) and drugs, G5Au NPs as the drug-loading satellites for deep tumor drug delivery and as catalase-like agents for relieving tumor hypoxia, doxorubicin (DOX) as the model chemotherapeutic drug loaded by both PDA and G5Au NPs, and polyethylene glycol (PEG) shells to improve biosafety. The developed drug-loaded nanovehicles (denoted as PDA-G5Au-PEG@DOX) can release G5Au satellites and DOX in stimuli-responsive manners. Thorough drug delivery in solid tumor can be realized via transporting DOX to the near-by area of and remote area from blood vessels by PDA and G5Au, respectively. Monitored by photoacoustic imaging and near-infrared fluorescence imaging, these PDA-G5Au-PEG@DOX NPs could accumulate in 4T1 tumor effectively. Under this guidance, significant tumor growth suppression could be achieved by the treatment of PDA-G5Au-PEG@DOX NPs plus laser without detectable side effects during the treatment period. The developed drug-loaded core-satellite nanovehicles with tumor microenvironment responsive/modulating capacities are of great potential in precise tumor treatments.

Construction of a Polypyrrole-Based Multifunctional Nanocomposite for Dual-Modal Imaging and Enhanced Synergistic Phototherapy against Cancer Cells.

Design and construction of multifunctional theranostic nanoplatforms are still desired for cancer-effective treatment. Herein, a kind of polypyrrole (PPy)-based multifunctional nanocomposite was designed and successfully constructed for dual-model imaging and enhanced synergistic phototherapy against cancer cells. Through graphene oxide (GO) sheet coating, PPy nanoparticles (NPs) were effectively combined with polyethylene glycol chains, Au NPs, and IR820 molecules. The obtained PGPAI NPs showed promising ability for photoacoustic/computed tomography imaging. Under near-infrared light irradiation, the PPy core and IR820 molecule effectively generated heat and reactive oxygen species (ROS), respectively. Furthermore, the loaded Au NPs owning catalase-like activity produced oxygen by decomposing H2O2 (up-regulated in tumor region), enhancing the oxygen-dependent photodynamic therapy efficacy. The formed PGPAI NPs were also proved to own desirable photothermal conversion efficiency, photothermal stability, colloidal stability, cytocompatibility, and cellular internalization behaviors. Furthermore, cell assay demonstrated that PGPAI NPs displayed enhanced synergistic phototherapy efficacy against cancer cells. These developed multifunctional nanoplatforms are promising for effective cancer theranostic applications.

Enhanced Photoacoustic and Photothermal Effect of Functionalized Polypyrrole Nanoparticles for Near-Infrared Theranostic Treatment of Tumor.

Functionalized nanomaterials with near-infrared (NIR) responsive capacity are quite promising for theranostic treatment of tumors, but formation of NIR responsive nanomaterials with enhanced theranostic ability and excellent biocompatibility is still very challenging. Herein, PEGylated indocyanine green (ICG)-loaded polypyrrole nanoparticles (PPI NPs) were designed and successfully formed through selecting polydopamine as the linkage between each component, demonstrating enhanced NIR responsive theranostic ability against tumor. By combining in vitro cell study with in vivo assay, the formed PPI NPs were proven to be fantastically biocompatible while effectively internalization in HeLa cells and retention in HeLa tumor were demonstrated by in vitro flow cytometry/confocal measurement and in vivo photoacoustic imaging assay. With the guidance of photoacoustic imaging, successful photothermal ablation of tumor was achieved by treatment with PPI NPs plus laser, which was much more effective than the group treated with NPs free of ICG. The combined enhanced photoacoustic and photothermal effect is mainly ascribed to the functionalized polypyrrole nanoparticles, which could accumulate in the tumor site more effectively with a relatively longer retention time taking advantage of the nanomaterial-induced endothelial leakiness phenomenon. All these results demonstrating that this designed PPI NPs possessing enhanced NIR responsive property hold great promise for tumor NIR theranostic applications.

A light-controllable specific drug delivery nanoplatform for targeted bimodal imaging-guided photothermal/chemo synergistic cancer therapy.

Breast cancer is a severe threat to the health and lives of women due to its difficult early diagnosis and the unsatisfactory therapeutic efficacy of breast cancer treatments. The development of theranostic strategies to combat breast cancer with high accuracy and effectiveness is therefore urgently needed. In this study, we describe a near-infrared (NIR) light-controllable, targeted and biocompatible drug delivery nanoplatform (PFH-PTX@PLGA/SPIO-Her) for photoacoustic (PA)/ultrasound (US) bimodal imaging-guided photothermal (PTT)/chemo synergistic cancer therapy of breast cancer. Carboxyl-modified PEGylated poly (lactic-co-glycolic acid) (PLGA-PEG-COOH) constituted the skeleton of the nanoplatform. Especially, the antibody Herceptin was modified onto the surface of nanoplatform for active HER2-targing to facilitate the tumor accumulation of the nanoplatform. The encapsulated superparamagnetic iron oxide (SPIO) nanoparticles could be employed as an excellent PA imaging agent to guide tumor therapy. When exposed to NIR light, the SPIO also could transform NIR light into thermal energy for photothermal ablation of tumor. The NIR-induced thermal effect subsequently triggered the optical droplet vaporization (ODV) of perfluorohexane (PFH) to generate PFH gas bubbles, which not only achieved the US imaging enhancement, but also contributed to the release of loaded paclitaxel (PTX) from the nanoplatform for significantly improving PTT therapeutic efficacy. Our results demonstrated that the targeted tumor accumulation, accurate real-time bimodal imaging, and the abundant drug release at the tumor site were all closely associated with the PTT therapeutic efficacy. Therefore, the theranostic nanoplatform is a very promising strategy for targeted imaging-guided photothermal/chemo synergistic tumor therapy with high therapeutic efficacy and minimized side effects. STATEMENT OF SIGNIFICANCE: Breast cancer is the most frequent cancer in women. Herein, we successfully developed a light-controllable and HER2 targeted theranostic nanoparticels (PFH-PTX@PLGA/SPIO-Her) as a specific drug delivery nanoplatform to overcome the low accuracy of tumor detection and the low specificity of traditional chemo-therapeutic protocols. The study demonstrated that PFH-PTX@PLGA/SPIO-Her could actively target to breast cancer cells with positive HER2 expression. The biocompatible PFH-PTX@PLGA/SPIO-Her nanoparticles as both photoacoustic/ultrasound bimodal imaging agents, photothermal-conversion nanomaterials (photothermal hyperthermia) and controllable drug delivery nanoagents (optical droplet vaporization) have completely eradicated the tumor without severe side effects. The theranostic strategy not only integrates strengthens of traditional imaging or therapeutic modalities, but also paves a new way for the efficient cancer treatment by taking the advantage of quickly-developing nanomedicine.