Bio-inspired self-assembled bacteriochlorin nanoparticles for superior visualization and photothermal ablation of tumors.

BACKGROUND: Although hyperthermia-based photothermal therapy (PTT) has achieved great success in the battle against malignant tumors, various commonly used photothermal sensitizers still suffer from non-selective tumor accumulation, limited photothermal conversion efficiency, potential toxicity and side effects, as well as complex and low cost-effective preparation process. Therefore, novel photothermal sensitizers are urgently required. The well-organized self-assembling of natural bacteriochlorophylls with superior photothermal property may provide an interesting option for the engineering of ideal PTS. METHODS: Inspired by the self-assembly peripheral light-harvesting antennas of natural bacteriochlorin in microorganisms, a biomimetic light-harvesting nanosystem (Nano-Bc) was developed via bacteriochlorophylls self-arranging in aqueous phase. The characterization of Nano-Bc were measured using DLS, TEM, UV-vis-near-infrared spectroscopy and preclinical PA imaging system. The cytotoxicity of Nano-Bc was quantitatively evaluated via a standard MTT assay using mouse breast cancer 4T1 cells, and the in vivo photothermal eradication of tumor was investigated in the 4T1 breast tumor-bearing mouse model. RESULTS: The obtained bacteriochlorin nanoparticles (Nano-Bc) exhibited ultra-high photothermal performance within the biological transparent window, showing superior heating capacity compared to commonly used photothermal sensitizers of organic dye indocyanine green and inorganic gold nanorods. Guiding by the inherent photoacoustic imaging of Nano-Bc, complete tumor elimination in vitro and vivo was evidenced upon laser irradiation. CONCLUSION: The green and facile preparation, ultra-high photothermal effect in the transparent window, excellent photoacoustic imaging capacity, and great biosafety prompt, the bio-inspired Nano-Bc as a promising theranostic platform against cancer in the areas of healthcare.

Rapidly analyzing of ingredients during chewing and processing of areca nut using feature-based molecular networking.

As a traditional herbal medicine and food in China and many other Asian countries, the areca nut (Areca catechu L.) is not only widely used for the treatment of various diseases, but also popular as a chewing hobby. However, as a first-class carcinogen designated by IARC, clinical studies have shown that long-term chewing of areca nut is associated with oral mucosal diseases and even oral cancer. Moreover, the incidence of these diseases varies regionally, suggesting that it may be related to edible methods in different regions. In this study, UPLC-Q-TOF-MSE was combined with feature-based molecular networking to systematically characterise the chemical ingredients of areca nut. Based on these results, the ingredients of different edible parts and edible methods was rapidly compared. The compositional changes during the production process were also analysed. The obtained results provide a foundation for the scientific utilisation of areca nut.

Artemisinin suppressed tumour growth and induced vascular normalisation in oral squamous cell carcinoma via inhibition of macrophage migration inhibitory factor.

BACKGROUND: Tumour vascular normalisation therapy advocates a balance between pro-angiogenic factors and anti-angiogenic factors in tumours. Artemisinin (ART), which is derived from traditional Chinese medicine, has been shown to inhibit tumour growth; however, the relationship between ART and tumour vascular normalisation in oral squamous cell carcinoma (OSCC) has not been previously reported. METHODS: Different concentrations(0 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg)of ART were used to treat the xenograft nude mice model of OSCC. The effects of ART on migration and proliferation of OSCC and human umbilical vein endothelial cells (HUVEC) cells were detected by scratch assay and CCK-8 assay. OSCC cells with macrophage migration inhibitory factor (MIF) silenced were constructed to explore the effect of MIF. RESULTS: Treatment with ART inhibited the growth and angiogenesis of OSCC xenografts in nude mice and downregulated vascular endothelial growth factor (VEGF), IL-8, and MIF expression levels. ART reduced the proliferation, migration, and tube formation of HUVEC, as well as the expression of VEGFR1 and VEGFR2. When the dose of ART was 50 mg/kg, vascular normalisation of OSCC xenografts was induced. Moreover, VEGF and IL-8 were needed in rhMIF restoring tumour growth and inhibit vascular normalisation after the addition of rhMIF to ART-treated cells. CONCLUSION: Artemisinin might induce vascular normalisation and inhibit tumour growth in OSCC through the MIF-signalling pathway.

Magnetic vortex nanoring coated with gadolinium oxide for highly enhanced T1-T2 dual-modality magnetic resonance imaging-guided magnetic hyperthermia cancer ablation.

Nowadays, about 30% of magnetic resonance imaging (MRI) exams need contrast agents (CAs) to improve the sensitivity and quality of the images for accurate diagnosis. Here, a multifunctional nano-agent with ring-like vortex-domain iron oxide as core and gadolinium oxide as shell (vortex nanoring Fe3O4 @Gd2O3, abbreviated as VNFG) was firstly designed and prepared for highly enhanced T1-T2 dual-modality magnetic resonance imaging (MRI)-guided magnetic thermal cancer therapy. After thorough characterization, the core-shell structure of VNFG was confirmed. Moreover, the excellent heat generation property (SAR=984.26 W/g) of the proposed VNFG under alternating magnetic fields was firmly demonstrated. Furthermore, both in vitro and in vivo studies have revealed a good preliminary indication of VNFG's biological compatibility, dual-modality enhancing feature and antitumor efficacy. This work demonstrates that the proposed VNFG can be a high-performance tumor diagnosis and theranostic treatment agent and may have great potential for clinical application in the future.

Genetically engineered magnetic nanocages for cancer magneto-catalytic theranostics.

The clinical applications of magnetic hyperthermia therapy (MHT) have been largely hindered by the poor magnetic-to-thermal conversion efficiency of MHT agents. Herein, we develop a facile and efficient strategy for engineering encapsulin-produced magnetic iron oxide nanocomposites (eMIONs) via a green biomineralization procedure. We demonstrate that eMIONs have excellent magnetic saturation and remnant magnetization properties, featuring superior magnetic-to-thermal conversion efficiency with an ultrahigh specific absorption rate of 2390 W/g to overcome the critical issues of MHT. We also show that eMIONs act as a nanozyme and have enhanced catalase-like activity in the presence of an alternative magnetic field, leading to tumor angiogenesis inhibition with a corresponding sharp decrease in the expression of HIF-1α. The inherent excellent magnetic-heat capability, coupled with catalysis-triggered tumor suppression, allows eMIONs to provide an MRI-guided magneto-catalytic combination therapy, which may open up a new avenue for bench-to-bed translational research of MHT.

Photoacoustic Imaging-Trackable Magnetic Microswimmers for Pathogenic Bacterial Infection Treatment.

Micro/nanorobots have been extensively explored as a tetherless small-scale robotic biodevice to perform minimally invasive interventions in hard-to-reach regions. Despite the emergence of versatile micro/nanorobots in recent years, matched in vivo development remains challenging, limited by unsatisfactory integration of core functions. Herein, we report a polydopamine (PDA)-coated magnetic microswimmer consisting of a magnetized Spirulina (MSP) matrix and PDA surface. Apart from the properties of the existing MSP (e.g., robust propulsion, natural fluorescence, tailored biodegradation, and selective cytotoxicity), the introduced PDA coating enhances the photoacoustic (PA) signal and photothermal effect of the MSP, thus making PA image tracking and photothermal therapy possible. Meanwhile, the PDA's innate fluorescence quenching and diverse surface reactivity allows an off-on fluorescence diagnosis with fluorescence probes (e.g., coumarin 7). As a proof of concept, real-time image tracking (by PA imaging) and desired theranostic capabilities of PDA-MSP microswimmer swarms are demonstrated for the treatment of pathogenic bacterial infection. Our study suggests a feasible antibacterial microrobot for in vivo development and a facile yet versatile functionalization strategy of micro/nanorobots.

Ultrasound-Switchable Nanozyme Augments Sonodynamic Therapy against Multidrug-Resistant Bacterial Infection.

Ultrasound (US)-driven sonodynamic therapy (SDT) has demonstrated wide application prospects in the eradication of deep-seated bacterial infections due to its noninvasiveness, site-confined irradiation, and high-tissue-penetrating capability. However, the ineffective accumulation of sonosensitizers at the infection site, the hypoxic microenvironment, as well as rapid depletion of oxygen during SDT greatly hamper the therapeutic efficacy of SDT. Herein, an US-switchable nanozyme system was proposed for the controllable generation of catalytic oxygen and sonosensitizer-mediated reactive oxygen species during ultrasound activation, thereby alleviating the hypoxia-associated barrier and augmenting SDT efficacy. This nanoplatform (Pd@Pt-T790) was easily prepared by bridging enzyme-catalytic Pd@Pt nanoplates with the organic sonosensitizer meso-tetra(4-carboxyphenyl)porphine (T790). It was really interesting to find that the modification of T790 onto Pd@Pt could significantly block the catalase-like activity of Pd@Pt, whereas upon US irradiation, the nanozyme activity was effectively recovered to catalyze the decomposition of endogenous H2O2 into O2. Such "blocking and activating" enzyme activity was particularly important for decreasing the potential toxicity and side effects of nanozymes on normal tissues and has potential to realize active, controllable, and disease-loci-specific nanozyme catalytic behavior. Taking advantage of this US-switchable enzyme activity, outstanding accumulation in infection sites, as well as excellent biocompatibility, the Pd@Pt-T790-based SDT nanosystem was successfully applied to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced myositis, and the sonodynamic therapeutic progression was noninvasively monitored by photoacoustic imaging and magnetic resonance imaging. The developed US-switchable nanoenzyme system provides a promising strategy for augmenting sonodynamic eradication of deep-seated bacterial infection actively, controllably, and precisely.

Zinc(II)-Dipicolylamine Coordination Nanotheranostics: Toward Synergistic Nanomedicine by Combined Photo/Gene Therapy.

We report the rational design of coordination-driven self-assembly metal-organic nanostructures for multifunctional nanotheranostics. Zinc(II) coordination-based nano-formulations capable of loading indocyanine green (ICG) and therapeutic genes were prepared to achieve a fluorescence/photoacoustic imaging-guided combination photo/gene therapy strategy. We showed the enhanced theranostic capability of zinc(II)-dipicolylamine-assisted assembly of ICG, as well as simultaneous targeted gene delivery in an experimental mouse model of cancer. Such a co-assembly strategy provides a facile way to achieve combined therapeutic functions for personalized nanomedicine.

The Hsp70 Gene Family in Solanum tuberosum: Genome-Wide Identification, Phylogeny, and Expression Patterns.

Heat shock protein 70 (Hsp70) family members play important roles in protecting plants against abiotic stresses, including salt, drought, heat, and cold. In this study, 20 putative StHsp70 genes were identified in potato (Solanum tuberosum L.) through the integration of the gene structures, chromosome locations, phylogenetic relationships, and expression profiles. These StHsp70 genes were classified into five sub-families based on phylogenetic analysis. Chromosome mapping revealed that they were unevenly and unequally distributed on 10 of the 12 chromosomes. Furthermore, segmental and tandem duplication events contributed to the expansion of the StHsp70 genes. Phylogenetic tree of the HSP70 genes from potato and other plant species revealed multiple sub-families. These findings indicated a common ancestor which had generated diverse sub-families prior to a mono-dicot split. In addition, expression analysis using RNA-seq revealed that the majority of these genes were expressed in at least one of the tested tissue, and were induced by Phytophthora infestans. Then, based on qRT-PCR analysis, the results showed that the transcript levels of some of the StHsp70 genes could be remarkably induced by such abiotic and hormone stresses, which indicated their potential roles in mediating the responses of potato plants to both abiotic and biotic stress conditions.

Self-Assembled Metal-Organic Nanoparticles for Multimodal Imaging-Guided Photothermal Therapy of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a high incidence of disease and the high recurrence rate is a major limitation for HCC treatment. To resolve such a challenge, multimodal imaging-guided photothermal therapy (PTT) provides a promising candidate for HCC treatment. Herein, we use a facile method to develop a novel self-assembled theranostic nanoparticle (NP) based on manganese irons (Mn2+) and indocyanine green (ICG) under the protection of poly(vinylpyrrolidone) (PVP). The fabricated NPs possess the properties of strong NIR optical absorbance, high photothermal conversion efficiency and multimodal imaging. Through intravenous injection, these NPs could highly accumulate in HepG2 tumor via the enhanced permeability and retention effect, as revealed by fluorescence/photoacoustic/magnetic resonance imaging, leading to an obviously improved in vivo therapeutic outcome. This study demonstrates that our self-assembled NPs could be a potential platform for multimodal imaging-guided PTT of HCC in future clinical therapy.

Photo-excitable hybrid nanocomposites for image-guided photo/TRAIL synergistic cancer therapy.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in cancer cells without toxicity to normal cells. However, the efficiency is greatly limited by its short half-life and wild resistance in various cancer cells. In this study, we reported a micellar hybrid nanoparticle to carry TRAIL ligand (denoted as IPN@TRAIL) for a novel photo-excited TRAIL therapy. These IPN@TRAIL offered increased TRAIL stability, prolonged half-life and enhanced tumor accumulation, monitored by dual mode imaging. Furthermore, IPN@TRAIL nanocomposites enhanced wrapped TRAIL therapeutic efficiency greatly towards resistant cancer cells by TRAIL nanovectorization. More importantly, when upon external laser, these nanocomposites not only triggered tumor photothermal therapy (PTT), but also upregulated the expression of death receptors (DR4 and DR5), resulting in a greater apoptosis mediated by co-delivered TRAIL ligand. Such photo/TRAIL synergistic effect showed its great killing effects in a controllable manner on TRAIL-resistant A549 tumor model bearing mice. Finally, these nanocomposites exhibited rapid clearance without obvious systemic toxicity. All these features rendered our nanocomposites a promising theranostic platform in cancer therapy.

Metalla-aromatic loaded magnetic nanoparticles for MRI/photoacoustic imaging-guided cancer phototherapy.

In this study, metalla-aromatic agents (MA) and a cluster of superparamagnetic iron oxide nanoparticles (SPIOs) were loaded inside a micellar carrier (Alkyl-PEI2k-PEG), resulting in MA/SPIOs@Alkyl-PEI2k-PEG nanoparticles (MASAs). The prepared MASAs with a photothermal transduction efficiency of 26.6% were also demonstrated as a potential photodynamic sensitizer to generate ROS effectively. Under the guidance of MRI/photoacoustic imaging, combined photothermal and photodynamic therapy achieved a synergistic anti-tumor effect, significantly improving the therapeutic efficacy of MASAs both in vitro and in vivo. This work shows that the developed MASAs are a potential theranostic agent for dual-modal imaging-guided cancer phototherapy.

Preparation of hypocrellin B nanocages in self-assembled apoferritin for enhanced intracellular uptake and photodynamic activity.

Photodynamic therapy (PDT) is a promising modality, which uses light energy to activate a nontoxic photosensitizer to treat various diseases like cancer and infectious diseases. Hypocrellin B (HB) is a naturally occurring photosensitizer isolated from traditional Chinese medicine Hypocrella bambusea. However, the high hydrophobicity and poor selectivity severely limit its application. Apoferritin, a macromolecular protein, can serve as an attractive nanocage to carry HB while improving its water solubility and tumor selectivity. In this study, novel HB-apoferritin nanoparticles (HB-AFT NPs) were successfully developed by assembling HB within the apoferritin nanocage. The self-assembled HB-AFT NPs have a narrow size distribution and smooth surface with an average diameter of 12 nm and a HB encapsulation efficiency of 85%. The morphological observation and circular dichroism analysis showed that the encapsulation strategy of HB did not impair apoferritin structure, and thus it potentially maintained the tumor targeting ability of apoferritin. Compared with free HB solution, HB-AFT NPs exhibited more pronounced photodynamic activity on MDA-MB-231 cells due to the higher intracellular uptake, increased reactive oxygen species (ROS) production and excellent tumor-targeting. All these results suggest that the self-assembled HB-AFT NPs can be considered as a potential photosensitive drug for tumor targeting photodynamic therapy.

Development of a folate-modified curcumin loaded micelle delivery system for cancer targeting.

Targeted drug delivery system for tumor cells is an appealing platform on enhancing the therapeutic effects and reducing the side effects of the drug. In this study, we developed folate-modified curcumin (Cur) loaded micelles (Cur-FPPs) for cancer chemotherapy. The targeting material, Folate-PEG3000-PLA2000, was synthesized by the amide bond formation reaction. And the Cur loaded micelles were prepared by thin-film hydration method with mPEG2000-PLA2000 (Cur-PPs) or mPEG2000-PLA2000 and Folate-PEG3000-PLA2000 (Cur-FPPs) as carrier. A central composite design (CCD) was used to optimize the formulation, and the optimized Cur-FPPs was prepared with the weight ratio of Folate-PEG3000-PLA2000 and mPEG2000-PLA2000 at 1:9. The average size of the mixed micelles was 70nm, the encapsulating efficiency and drug-loading were 80.73±0.16% and 4.84±0.01%, respectively. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-FPPs showed a sustained manner. Furthermore, the in vitro cytotoxicity and cellular uptake of Cur-FPPs were significantly enhanced towards MCF-7 and HepG2 cells. The pharmacokinetic studies in rats indicated that a 3-fold increase in the half-life was achieved for Cur loaded micelle formulations relative to solubilized Cur. All the results demonstrated that folate-modified Cur micelles could serve as a potential nanocarrier to improve the solubility and anti-cancer activity of Cur.

[Primary study on rapid propagation of Curcuma xanthorrhiza].

Using the rhizome of Curcuma xanthorrhiza Roxb. as explant to induce the adventitious bud, multiplication and radication. The results showed that the inducing and differentiating of bud was better on MS + 6-BA 1.0 mg/L + NAA 0.5 mg/L, the multiplication of bud was on MS+6-BA 1.2 mg/L + NAA 0.l mg/L and the redication was on 1/2 MS + NAA 0.5 mg/L.