Phytochemistry and Pharmacology of Sesquiterpenoids from Atractylodes DC. Genus Rhizomes.

The rhizomes of the genus Atractylodes DC. consist of various bioactive components, including sesquiterpenes, which have attracted a great deal of research interest in recent years. In the present study, we reviewed the previously published literatures prior to November 2023 on the chemical structures, biosynthetic pathways, and pharmacological activities of the sesquiterpenoids from this genus via online databases such as Web of Science, Google Scholar, and ScienceDirect. Phytochemical studies have led to the identification of more than 160 sesquiterpenes, notably eudesmane-type sesquiterpenes. Many pharmacological activities have been demonstrated, particularly anticancer, anti-inflammatory, and antibacterial and antiviral activities. This review presents updated, comprehensive and categorized information on the phytochemistry and pharmacology of sesquiterpenes in Atractylodes DC., with the aim of offering guidance for the future exploitation and utilization of active ingredients in this genus.

Creating a new yellow and blue combination transparent film for Panax ginseng C.A. Meyer growth based on orthogonal designs.

Panax ginseng C.A. Meyer originates from old-growth forest environments, where the light intensity and spectrum reaching the forest bed are influenced by the canopy and humidity. In farmlands, suitable light intensity for cultivation is achieved by controlling the light transmission rate using shading nets, while light quality is regulated by a cover of yellow or blue transparent film. Such films have a light quality distinct from that produced by old-growth forests. Herein, a large composite film was developed by alternating small pieces of yellow and blue transparent film. An orthogonal array was used to evaluate the influence of the small transparent film area (STFA), yellow transparent film (YTF) number, and blue transparent film (BTF) number on the associated changes in ginseng in a range of fluorescence-, photosynthesis-, morphology-, and crop quality-related factors. Our results showed that light intensity was influenced primarily by STFA, which caused an overall decrease, while the light quality ratio was affected primarily by YTF number, which increased the proportion of red light and decreased that of blue light, with corresponding influence on different growth parameters. Based on these observations, an improved yellow and blue combination transparent film (YBCTF) with the following characteristics was established: STFA: 15 × 15 cm, YTF: two pieces, and BTF: three pieces. The improved YBCTF facilitated efficient light energy use by the plants, and led to an increase in leaf area, the per leaf photosynthetic rate, dry root weight, and the per root single ginsenoside yield. The findings present a relatively low-cost approach for optimising the light environment of ginseng cultivated in farmland and other crops in large-scale agricultural settings.

Biochar derivation at low temperature: A novel strategy for harmful resource usage of antibiotic mycelial dreg.

Antibiotic mycelial dreg (AMD) has been categorized as hazardous waste due to the high residual hazardous contaminants. Inappropriate management and disposal of AMD can cause potential environmental and ecological risks. In this study, the potential of pleuromutilin mycelial dreg (PMD) as a novel feedstock for preparing tetracycline hydrochloride (TC) adsorbent was explored to achieve safe management of PMD. The results suggested that residual hazardous contaminants were completely eliminated after pyrolysis. With the increase of pyrolysis temperature, the yields, H/C, O/C, (O + N)/C, and pore size in PMD-derived biochars (PMD-BCs) decreased, while BET surface area and pore volume increased, resulting in the higher stability of the PMD-BCs prepared from higher temperatures. The TC adsorption of the PMD-BCs increased from 27.3 to 46.9 mg/g with the increase of the pyrolysis temperature. Surprisingly, pH value had a strong impact on the TC adsorption, the adsorption capacity of BC-450 increased from 6.5 to 71.1 mg/g when the solution pH value increased from 2 to 10. Lewis acid-base interaction, pore filling, π-π interaction, hydrophobic interaction, and charge-assisted hydrogen bond (CAHB) are considered to drive the adsorption. This work provides a novel pathway for the concurrent detoxification and reutilization of AMD.

Development and validation of KASP markers for resistance to Phytophthora capsici in Capsicum annuum L.

Resistance of Capsicum annuum to Phytophthora blight is dependent on the genetic background of the resistance source and the Phytophthora capsici isolate, which poses challenges for development of generally applicable molecular markers for marker-assisted selection. In this study, the resistance to P. capsici of C. annuum was genetically mapped to chromosome 5 within a 1.68-Mb interval by genome-wide association study analysis of 237 accessions. In this candidate region, 30 KASP markers were developed using genome resequencing data for a P. capsici-resistant line (0601 M) and a susceptible line (77,013). Seven of these KASP markers, located in the coding region of a probable leucine-rich repeats receptor-like serine/threonine-protein kinase gene (Capana05g000704), were validated in the 237 accessions, which showed an average accuracy of 82.7%. The genotyping of the seven KASP markers strongly corresponded with the phenotype of 42 individual plants in a pedigree family (PC83-163) developed from the P. capsici-resistant line CM334. This research provides a set of efficient and high-throughput KASP markers for marker-assisted selection of resistance to P. capsici in C. annuum. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01367-3.

Pepper variome reveals the history and key loci associated with fruit domestication and diversification.

Pepper (Capsicum spp.) is an important vegetable crop that provides a unique pungent sensation when eaten. Through construction of a pepper variome map, we examined the main groups that emerged during domestication and breeding of C. annuum, their relationships and temporal succession, and the molecular events underlying the main transitions. The results showed that the initial differentiation in fruit shape and pungency, increase in fruit weight, and transition from erect to pendent fruits, as well as the recent appearance of large, blocky, sweet fruits (bell peppers), were accompanied by strong selection/fixation of key alleles and introgressions in two large genomic regions. Furthermore, we identified Up, which encodes a BIG GRAIN protein involved in auxin transport, as a key domestication gene that controls erect vs pendent fruit orientation. The up mutation gained increased expression especially in the fruit pedicel through a 579-bp sequence deletion in its 5' upstream region, resulting in the phenotype of pendent fruit. The function of Up was confirmed by virus-induced gene silencing. Taken together, these findings constitute a cornerstone for understanding the domestication and differentiation of a key horticultural crop.

HSP70-Promoter-Driven CRISPR/Cas9 System Activated by Reactive Oxygen Species for Multifaceted Anticancer Immune Response and Potentiated Immunotherapy.

To address the low response rate to immune checkpoint blockade (ICB) therapy, we propose a specific promoter-driven CRISPR/Cas9 system, F-PC/pHCP, that achieves permanent genomic disruption of PD-L1 and elicits a multifaceted anticancer immune response to potentiate immunotherapy. This system consists of a chlorin e6-encapsulated fluorinated dendrimer and HSP70-promoter-driven CRISPR/Cas9. F-PC/pHCP under 660 nm laser activated the HSP70 promoter and enabled the specific expression of the Cas9 protein to disrupt the PD-L1 gene, preventing immune escape. Moreover, F-PC/pHCP also induced immunogenic cell death (ICD) of tumor cells and reprogrammed the immunosuppressive tumor microenvironment. Overall, this specific promoter-driven CRISPR/Cas9 system showed great anticancer efficacy and, more importantly, stimulated an immune memory response to inhibit distant tumor growth and lung metastasis. This CRISPR/Cas9 system represents an alternative strategy for ICB therapy as well as enhanced cancer immunotherapy.

Fine mapping of Rf2, a minor Restorer-of-fertility (Rf) gene for cytoplasmic male sterility in chili pepper G164 (Capsicum annuum L.).

KEY MESSAGE: Genome re-sequencing and recombination analyses identified Capana06g000193 as a strong candidate for the minor male fertility restoration locus Rf2 in chili pepper G164 harboring two dominant male fertility restoration genes. Male fertility restoration genes of chili pepper restorer line G164 (Capsicum annuum L.) were studied using molecular marker genotypes of an F2 population (7G) of G164 crossed with the cytoplasmic male sterility line 77013A. The ratio of sterile to fertile single plants in the F2 population was 1:15. This result indicates that chili pepper G164 has two dominant restoration genes, which we designated as Rf1 and Rf2. An individual plant recessive for Rf1 and heterozygous for Rf2, 7G-112 (rf1rf1Rf2rf2), was identified by molecular marker selection and genetic analysis, and a single Rf2 gene-segregating population with a 3:1 ratio of fertile to sterile plants was developed from the self-pollination of male fertile individuals of 77013A and 7G-112 hybrid progeny. Bulk segregant analysis of fertile and sterile pools from the segregating populations was used to genetically map Rf2 to a 3.1-Mb region on chromosome 6. Rf2 was further narrowed to a 179.3-kb interval through recombination analysis of molecular markers and obtained the most likely candidate gene, Capana06g000193.

Response of microbial community structure to chromium contamination in Panax ginseng-growing soil.

Chromium (Cr) contamination in soil poses a serious security risk for the development of medicine and food with ginseng as the raw material. Microbiome are critical players in the functioning and service of soil ecosystems, but their feedback to Cr-contaminated ginseng growth is still poorly understood. To study this hypothesis, we evaluated the effects of microbiome and different Cr exposure on the soil microbial community using Illumina HiSeq high-throughput sequencing. Our results indicated that 2467 OTUs and 1785 OTUs were obtained in 16S and ITS1 based on 97% sequence similarity, respectively. Bacterial and fungal diversity were affected significantly in Cr-contaminated soil. Besides, Cr contamination significantly changed the composition of the soil bacterial and fungal communities, and some biomarkers were identified in the different classification level of the different Cr-contaminated treatments using LEfSe. Finally, a heatmap of Spearman's rank correlation coefficients and canonical discriminant analysis (CDA) indicated that Chloroflexi, Gemmatimonadetes, Acidobacteria, Verrucomicobia, and Parcubacteria in phylum level and Acidimicrobiia, Gemmatimonadetes, and Deltaproteobacteria in class level were positively correlated with AK, AP, and NO3--N (p < 0.05 or p < 0.01), but negatively correlated with total Cr and available Cr (p < 0.05 or p < 0.01). Similarly, in the fungal community, Tubaria, Mortierellaceae, and Rhizophagus in the phylum level and Glomeromycetes, Agaricomycetes, and Exobasidiomycetes in the class level were positively correlated with AK, AP, and NO3--N (p < 0.05 or p < 0.01), but negatively correlated with total Cr and available Cr (p < 0.05 or p < 0.01). Our findings provide new insight into the effects of Cr contamination on the microbial communities in ginseng-growing soil.

Effects of cadmium contamination on bacterial and fungal communities in Panax ginseng-growing soil.

BACKGROUND: Cadmium (Cd) contamination in soil poses a serious safety risk for the development of medicine and food with ginseng as the raw material. Microorganisms are key players in the functioning and service of soil ecosystems, but the effects of Cd-contaminated ginseng growth on these microorganisms is still poorly understood. To study this hypothesis, we evaluated the effects of microorganisms and Cd (0, 0.25, 0.5, 1.0, 2.0, 5.0, and 10.0 mg kg-1 of Cd) exposure on the soil microbial community using Illumina HiSeq high-throughput sequencing. RESULTS: Our results indicated that Cd-contaminated soil affected the soil microbial diversity and composition, and bacterial diversity was affected more than fungal diversity in Cd-contaminated soil, especially according to Shannon indices. The abundance of the soil microbial community decreased and the composition changed according to the relative abundances at the phylum level, including those of Saccharibacteria and Gemmatimonadetes in bacteria and Mortierellomycota in fungi. The LEfSe algorithm was used to identify active biomarkers, and 45 differentially abundant bacterial taxonomic clades and 16 differentially abundant fungal taxonomic clades were identified with LDA scores higher than 4.0. Finally, a heatmap of Spearman's rank correlation coefficients and canonical discriminant analysis (CDA) indicated that some key biomarkers, Arenimonas, Xanthomonadales, Nitrosomonadaceae, Methylophilales, Caulobacterales, Aeromicrobium, Chitinophagaceae, Acidimicrobiales, Nocardioidaceae, Propionibacteriales, Frankiales, and Gemmatimonadaceae, were positively correlated with the total and available Cd (p<0.05) but negatively correlated with AK, AP, and pH (p<0.05) in the bacterial community. Similarly, in the fungal community, Tubaria, Mortierellaceae, and Rhizophagus were positively correlated with the total and available Cd but negatively correlated with AK, AP, TK, and pH. CONCLUSION: Cd contamination significantly affected microbial diversity and composition in ginseng-growing soil. Our findings provide new insight into the effects of Cd contamination on the microbial communities in ginseng-growing soil.

A siRNA-Assisted Assembly Strategy to Simultaneously Suppress "Self" and Upregulate "Eat-Me" Signals for Nanoenabled Chemo-Immunotherapy.

Effectively activating macrophages that can engulf cancer cells is a promising immunotherapeutic strategy but remains a major challenge due to the expression of "self" signals (e.g., CD47 molecules) by tumor cells to prevent phagocytosis. Herein, we explored a siRNA-assisted assembly strategy for the simultaneous delivery of siRNA and mitoxantrone hydrochloride (MTO·2HCl) via PLGA-based nanoparticles. The siRNA suppressed a "self" signal by silencing the CD47 gene, while the MTO induced surface exposure of calreticulin (CRT) to provide an "eat-me" signal. The siRNA-assisted assembly strategy synergistically increased the phagocytosis of tumor cells by macrophages, promoted effective antigen presentation, and initiated T cell-mediated immune responses in two aggressive tumor animal models of melanoma and colon cancer, eventually achieving significantly improved antitumor activity. This study provides a straightforward codelivery strategy to simultaneously suppress "self" and upregulate "eat-me" signals to potentiate macrophage-mediated immunotherapy.

The osteogenic differentiation of human bone marrow stromal cells induced by nanofiber scaffolds using bioinformatics.

This article aims to investigate the mechanism of behaviors of human bone marrow stromal cells (hBMSCs) affected by scaffold structure combining Monte Carlo feature selection (MFCS), incremental feature selection (IFS) and support vector machine (SVM). The specific differentially expressed genes (DEGs) of hBMSCs cultured on nanofiber (NF) scaffolds and freeform fabrication (FFF) scaffolds were obtained. Key genes were screened from common genes between osteogenic DEGs and NF specific DEGs with MFCS, IFS and SVM. The results demonstrated that NF scaffolds induced hBMSCs to express more genes related to osteogenic differentiation. Finally, 16 key genes were identified among the common genes. The common genes were significantly enriched in Rap1 signaling pathway, extracellular matrix and ossification. The results in this study suggested that the gene expression of hBMSCs was sensitive to NF scaffolds and FFF scaffolds, and the osteogenic differentiation of hBMSCs could be enhanced by NF scaffolds.

Injectable hydrogel-mediated combination of hyperthermia ablation and photo-enhanced chemotherapy in the NIR-II window for tumor eradication.

Local administration of therapeutic agents with long-term retention capabilities efficiently avoids nonspecific distribution in normal organs with an increased drug concentration in pathological tissue. Herein, we developed an injectable and degradable alginate-calcium (Ca2+) hydrogel for the local administration of corn-like Au/Ag nanorods (NRs) and doxorubicin hydrochloride (DOX·HCl). The immobilized Au/Ag NRs with strong absorbance in the near-infrared II (NIR-II) window efficiently ablated the majority of tumor cells after 1064 nm laser irradiation and triggered the release of DOX to kill residual tumor cells. As a result, injectable hydrogel-mediated NIR-II photothermal therapy (PTT) and chemotherapy efficiently inhibited tumor growth, resulting in the complete eradication of tumors in most of the treated mice. Furthermore, owing to the confinement of the Au/Ag NRs and DOX·HCl within the hydrogel, such treatment exhibited excellent biocompatibility.

Anticancer property of Hemp Bioactive Peptides in Hep3B liver cancer cells through Akt/GSK3ß/ß-catenin signaling pathway.

Foodborne protein hydrolysates exhibit biological activity that may be therapeutic in a number of human disease settings. Hemp peptides (HP) generated by controlled hydrolysis of hemp proteins have a number of health benefits and are of pharmaceutical value. In the present study, we produce small molecular weight HP from hemp seed and investigate its anticancer properties in Hep3B human liver cancer cells. We demonstrate that HP treatment increased apoptosis, reduced cell viability, and reduced cell migration in Hep3B human liver cancer cells without affecting the normal liver cell line L02. We correlate these phenotypes with increased cellular ROS levels, upregulation of cleaved caspase 3 and Bad, and downregulation of antiapoptotic Bcl-2. HP treatment led to increased Akt and GSK-3ß phosphorylation, with subsequent downregulation of ß-catenin, suggesting ß-catenin signaling modulation as a critical mechanism by which HP exhibits anticancer properties. Our findings suggest HP are of potential therapeutic interest for liver cancer treatment.

Development and application of KASP markers associated with Restorer-of-fertility gene in Capsicum annuum L.

Fertility restoration of cytoplasmic male sterility (CMS) in Capsicum annuum is controlled by multiple alleles of Restorer-of-fertility (Rf) genes. The isolation of additional Rf genes should therefore enrich the knowledge of CMS/Rf systems and accelerate their exploitation in hybrid seed production. In this study, the fertility restorer gene CaRfm of '0601 M', a non-pungent bell pepper, was genetically mapped to a 1.2-cM region flanked by KASP markers S761 and S183. CaRfm was then physically mapped to a 128.96-Kb interval predicted from 24 recombinants with two co-segregated markers, S423 and S424. CaPPR6 encoding a pentatricopeptide repeat (PPR) protein was suggested as the most likely candidate gene for the CaRfm locus on the basis of sequence alignment as well as genotyping of tightly linked markers. In addition, molecular markers S1597 and S1609, which are immediately adjacent to CaRfm at 15.7 and 57.8-Kb respectively, were developed and applied to marker-assisted selection. The results provided friendly markers for breeding pepper restorer lines and laid the foundation for elucidating the male fertility restoration mechanism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01109-9.

Fine mapping of the major anthracnose resistance QTL AnRGO5 in Capsicum chinense 'PBC932'.

BACKGROUND: Colletotrichum species are the causal agents of anthracnose, a major disease affecting the yield and quality of pepper (Capsicum spp.). Colletotrichum scovillei is widespread in China, has strong pathogenicity and drug resistance, and causes anthracnose disease in pepper fruits that severely reduces production. Previously, an anti-anthracnose locus AnRGO5 was mapped to the P5 chromosome on the basis of analyses of fruit at the green mature stage. The aim of this study was to narrow down the interval of this locus and identify the gene responsible for conferring resistance. RESULTS: On the basis of results of re-sequencing of Capsicum chinense 'PBC932' and C. annuum '77013', we developed Kompetitive allele-specific PCR (KASPar) markers and insertion-deletion (InDel) markers linked to AnRGO5 at the green mature fruit stage and used them to construct a genetic linkage map (42 markers, 24.4 cM in length). Using data obtained in phenotypic and genotypic analyses of BC4S1, BC4S2, and BC4S3 populations, AnRGO5 was located between the markers P5in-2266-404 and P5in-2268-978 within a physical distance of 164 kb. This region contained five genes, including CA05g17730. CA05g17730 encodes 'R1C-3-like' putative late blight resistance protein homologs. The transcript level of CA05g17730 differed between 'PBC932' and '77013'. The structure of the CA05g17730 gene also differed between 'PBC932' and '77013'. CONCLUSIONS: We narrowed down the QTL interval to a region containing five genes. These results will be useful for further research on the mechanisms of resistance to anthracnose, and for marker assisted selection for anthracnose-resistant capsicum lines.

Fine mapping of the male fertility restoration gene CaRf032 in Capsicum annuum L.

KEY MESSAGE: A novel strong candidate gene CA00g82510 for the male fertility restoration locus CaRf032 in Capsicum annuum was identified by genome re-sequencing and recombination analysis. A single dominant locus (CaRf032) for fertility restoration of cytoplasmic male sterility was identified in the strong restorer inbred line IVF2014032 of chili pepper (Capsicum annuum L.). CaRf032 was localized within an 8.81-Mb candidate intervals on chromosome 6 using bulked segregant analysis based on high-throughput sequencing data. Subsequently, the candidate interval was genetically mapped and defined to a 249.41-kb region using an F2 population of 441 individuals generated by crossing the male-sterile line 77013A and the restorer line IVF2014032. To fine map CaRf032, eight newly developed KASP markers were used to genotype 23 recombinants screened from a larger F2 population of 2877 individuals. The CaRf032 locus was localized to a 148.05-kb region between the KASP markers S1402 and S1354, which was predicted to contain 22 open reading frames (ORFs). One ORF with an incomplete sequence was predicted to contain a PPR motif, and its physical position overlapped with the Rf candidate gene CaPPR6_46. The PPR ORF sequence before the gap showed 100% identity with the CA00g82510 locus of the CM334 reference genome. CA00g82510 encodes a protein of 583 amino acids, containing 14 PPR motifs, and shows significantly differential expression between the flower buds of the maintainer line 77013 and the restorer line IVF2014032. These results indicated that CA00g82510 is a strong candidate gene for CaRf032. Five KASP markers, which detected single-nucleotide polymorphisms in CA00g82510 of 77013 and IVF2014032, co-segregated with CaRf032 and showed 64.4% successful genotyping of 38 maintainer and 63 restorer lines.

A predicted NEDD8 conjugating enzyme gene identified as a Capsicum candidate Rf gene using bulk segregant RNA sequencing.

Cytoplasmic male sterility (CMS) is an important tool for producing F1 hybrids, which can exhibit heterosis. The companion system, restorer-of-fertility (Rf), is poorly understood at the molecular level and would be valuable in producing restorer lines for hybrid seed production. The identity of the Rf gene in Capsicum (pepper) is currently unclear. In this study, using bulked segregant RNA sequencing (BSR-seq), a strong candidate Rf gene, Capana06g002866, which is annotated as a NEDD8 conjugating enzyme E2, was identified. Capana06g002866 has an ORF of 555 bp in length encoding 184 amino acids; it can be cloned from F1 plants from the hybridization of the CMS line 8A and restorer line R1 but is not found in CMS line 8A. With qRT-PCR validation, Capana06g002866 was found to be upregulated in restorer accessions compared to sterile accessions. The relative expression in flower buds increased with the developmental stage in F1 plants, while the expression was very low in all flower bud stages of the CMS lines. These results provide new insights into the Rf gene in pepper and will be useful for other crops utilizing the CMS system.

Promising positive liver targeting delivery system based on arabinogalactan-anchored polymeric micelles of norcantharidin.

Liver cancer is the third most common cause of global cancer-related deaths. This study focused on newly developed drug delivery systems with hepatocyte asialoglycoprotein receptor binding targeting the liver. Although norcantharidin (NCTD) is effective in primary liver cancer treatment, its toxicity in the urinary system remains. Positive liver-targeting effect could be achieved by preparing polymer micelles by arabinogalactan on the surface of N-(4-methylimidazole)-hydroxyethyl-chitosan (MHC). HepG2 cells were used to analyze the cytotoxicity, invasion, apoptosis and uptake of NCTD-loaded micelles. The in vivo antitumor efficacy of NCTD-M was evaluated using tumor-bearing nude mice. Successful preparation of NCTD-M was shown. In vivo imaging showed that micelles significantly increased positive liver drug targeting. Laser confocal microscopy showed increased cellular uptake of micelles. NCTD-M also enhanced cell invasion and the proportion of apoptotic cells. Compared with the other groups, the micelles showed better antitumor effects in vivo. Therefore, the positive liver-targeting NCTD-M, which can enhance antitumor efficacy and reduce toxicity, could be a promising and effective therapeutic agent for liver cancer treatment.

Fe3O4@Au composite magnetic nanoparticles modified with cetuximab for targeted magneto-photothermal therapy of glioma cells.

BACKGROUND: Thermoresponsive nanoparticles have become an attractive candidate for designing combined multimodal therapy strategies because of the onset of hyperthermia and their advantages in synergistic cancer treatment. In this paper, novel cetuximab (C225)-encapsulated core-shell Fe3O4@Au magnetic nanoparticles (Fe3O4@Au-C225 composite-targeted MNPs) were created and applied as a therapeutic nanocarrier to conduct targeted magneto-photothermal therapy against glioma cells. METHODS: The core-shell Fe3O4@Au magnetic nanoparticles (MNPs) were prepared, and then C225 was further absorbed to synthesize Fe3O4@Au-C225 composite-targeted MNPs. Their morphology, mean particle size, zeta potential, optical property, magnetic property and thermal dynamic profiles were characterized. After that, the glioma-destructive effect of magnetic fluid hyperthermia (MFH) combined with near-infrared (NIR) hyperthermia mediated by Fe3O4@Au-C225 composite-targeted MNPs was evaluated through in vitro and in vivo experiments. RESULTS: The inhibitory and apoptotic rates of Fe3O4@Au-C225 composite-targeted MNPs-mediated combined hyperthermia (MFH+NIR) group were significantly higher than other groups in vitro and the marked upregulation of caspase-3, caspase-8, and caspase-9 expression indicated excellent antitumor effect by inducing intrinsic apoptosis. Furthermore, Fe3O4@Au-C225 composite-targeted MNPs-mediated combined hyperthermia (MFH+NIR) group exhibited significant tumor growth suppression compared with other groups in vivo. CONCLUSION: Our studies illustrated that Fe3O4@Au-C225 composite-targeted MNPs have great potential as a promising nanoplatform for human glioma therapy and could be of great value in medical use in the future.

Evaluation of in vitro and in vivo antitumor effects of gambogic acid-loaded layer-by-layer self-assembled micelles.

This study aimed to develop a novel type of multilayer micelle using protamine (PRM) and hyaluronic acid (HA) for the delivery of gambogic acid (GA). GA-loaded micelles (GA-M) were simply andrapidly prepared using lecithin/solutol HS15 using a film-dispersion method. PRM and HA were added in sequence to form layer-by-layer self-assembled micelles (HA-PRM-GA-M), in which particle size, zeta potential, particle morphology, drug loading, encapsulation efficiency, and in vitro release were investigated. Surface charge reversal demonstrated that rapid HA detachment exposed PRM, leading to activation of a "proton sponge" effect in the hyaluronidase (HAase)-rich tumor microenvironment. Compared with coumarin 6-loaded micelles (C6-M), more efficient intracellular trafficking was observed for HA-PRM-C6-M, which is associated with the endosomal/lysosomal escaping ability of the exposed PRM. In vivo imaging showed increased enrichment of near infrared fluorescent dye (DIR)-loaded HA-PRM-DIR-M at the tumor site, suggesting that HA enhanced the active tumor targeting of GA. Furthermore, HA-PRM-GA-M showed the stronger antitumor activity than GA and GA-M against human lung adenocarcinoma (A549) tumor xenografts in nude mice. In summary, our findings show the potential of HA-PRM-GA-M as a novel intravenous drug carrier for the treatment of lung cancer.