Pancreatic ductal adenocarcinoma is characterised by a dense desmoplastic stroma composed of stromal cells and extracellular matrix (ECM). This barrier severely impairs drug delivery and penetration. ...Activated pancreatic stellate cells (PSCs) play a key role in establishing this unique pathological obstacle, but also offer a potential target for anti-tumour therapy. Here, we construct a tumour microenvironment-responsive nanosystem, based on PEGylated polyethylenimine-coated gold nanoparticles, and utilise it to co-deliver all-trans retinoic acid (ATRA, an inducer of PSC quiescence) and siRNA targeting heat shock protein 47 (HSP47, a collagen-specific molecular chaperone) to re-educate PSCs. The nanosystem simultaneously induces PSC quiescence and inhibits ECM hyperplasia, thereby promoting drug delivery to pancreatic tumours and significantly enhancing the anti-tumour efficacy of chemotherapeutics. Our combination strategy to restore homoeostatic stromal function by targeting activated PSCs represents a promising approach to improving the efficacy of chemotherapy and other therapeutic modalities in a wide range of stroma-rich tumours.
Iron is an essential element for cell proliferation and homeostasis by engaging in cell metabolism including DNA synthesis, cell cycle, and redox cycling; however, iron overload could contribute to ...tumor initiation, proliferation, metastasis, and angiogenesis. Therefore, manipulating iron metabolisms, such as using iron chelators, transferrin receptor 1 (TFR1) Abs, and cytotoxic ligands conjugated to transferrin, has become a considerable strategy for cancer therapy. However, there remain major limitations for potential translation to the clinic based on the regulation of iron metabolism in cancer treatment. Nanotechnology has made great advances for cancer treatment by improving the therapeutic potential and lowering the side‐effects of the proved drugs and those under various stages of development. Early studies that combined nanotechnology with therapeutic means for the regulation of iron metabolism have shown certain promise for developing specific treatment options based on the intervention of cancer iron acquisition, transportation, and utilization. In this review, we summarize the current understanding of iron metabolism involved in cancer and review the recent advances in iron‐regulatory nanotherapeutics for improved cancer therapy. We also envision the future development of nanotherapeutics for improved treatment for certain types of cancers.
We summarize the current understanding of iron metabolism involved in cancer and review the recent advances in iron‐regulatory nanotherapeutics for improved cancer therapy. We also envision the future development of nanotherapeutics for improved treatment for certain types of cancers.
An effective tumor vaccine vector that can rapidly display neoantigens is urgently needed. Outer membrane vesicles (OMVs) can strongly activate the innate immune system and are qualified as ...immunoadjuvants. Here, we describe a versatile OMV-based vaccine platform to elicit a specific anti-tumor immune response via specifically presenting antigens onto OMV surface. We first display tumor antigens on the OMVs surface by fusing with ClyA protein, and then simplify the antigen display process by employing a Plug-and-Display system comprising the tag/catcher protein pairs. OMVs decorated with different protein catchers can simultaneously display multiple, distinct tumor antigens to elicit a synergistic antitumour immune response. In addition, the bioengineered OMVs loaded with different tumor antigens can abrogate lung melanoma metastasis and inhibit subcutaneous colorectal cancer growth. The ability of the bioengineered OMV-based platform to rapidly and simultaneously display antigens may facilitate the development of these agents for personalized tumour vaccines.
Due to their ability to elicit a potent immune reaction with low systemic toxicity, cancer vaccines represent a promising strategy for treating tumors. Considerable effort has been directed toward ...improving the in vivo efficacy of cancer vaccines, with direct lymph node (LN) targeting being the most promising approach. Here, a click‐chemistry‐based active LN accumulation system (ALAS) is developed by surface modification of lymphatic endothelial cells with an azide group, which provide targets for dibenzocyclooctyne (DBCO)‐modified liposomes, to improve the delivery of encapsulated antigen and adjuvant to LNs. When loading with OVA257–264 peptide and poly(I:C), the formulation elicits an enhanced CD8+ T cell response in vivo, resulting in a much more efficient therapeutic effect and prolonged median survival of mice. Compared to treatment with DBCO‐conjugated liposomes (DL)‐Ag/Ad without the azide targeting, the percent survival of ALAS‐vaccine‐treated mice improves by 100% over 60 days. Altogether, the findings indicate that the novel ALAS approach is a powerful strategy to deliver vaccine components to LNs for enhanced antitumor immunity.
A click‐chemistry‐based active lymph node (LN) accumulation system is developed by surface modification of lymphatic endothelial cells with azide groups, which provide targets for dibenzocyclooctyne (DBCO)‐modified liposomes, to improve the delivery of encapsulated cargoes to LNs. When loading with antigens and adjuvants, the formulation elicits an enhanced immune response, resulting in a much more efficient therapeutic effect and prolonged survival of mice.
•The release principle of organic compounds is associated to coal structure during pyrolysis.•The release amounts of PAHs and phenols has different trend as coal rank increased.•The formation ...mechanisms of PAHs and phenols are proposed during coal pyrolysis.
A considerable amount of organic compounds could be released during coal utilization processes, and these compounds could have a significant detrimental effect on the environment and human health if freely discharged. In this study, we investigated the yields of two organic compounds (PAHs and phenols) released during the pyrolysis of coals with different ranks. And then, the formation mechanisms of PAHs and phenols are discussed by means of comparisons the correlation between release principles and coal structure. The results showed that the yields of PAHs and phenols depended to a large extent on coal structure. PAHs are formed not only by thermal breakdown of coal structure, but also by the combination of different low molecule weight compounds with each other. Monohydric phenolic carbon and aromatic ether carbon were likely to be the precursor structure of phenols. The formation of phenol, cresol and xylenol are closely related to the types of free radical (like H or CH3) and the chemical structure of oxygenated aromatic carbon in coal during pyrolysis.
A novel cleavable amphiphilic peptide (CAP) was designed to be specifically responsive to fibroblast activation protein‐α (FAP‐α), a protease specifically expressed on the surface of ...cancer‐associated fibroblasts. The CAP self‐assembled into fiber‐like nanostructures in solution, while the presence of hydrophobic chemotherapeutic drugs readily transformed the assemblies into drug‐loaded spherical nanoparticles. The disassembly of these nanoparticles (CAP‐NPs) upon FAP‐α cleavage resulted in rapid and efficient release of the encapsulated drugs specifically at tumor sites. This Transformers‐like drug delivery strategy could allow them to disrupt the stromal barrier and enhance local drug accumulation. Therapeutic results suggested that drug‐loaded CAP‐NPs hold promising tumor specificity and therapeutic efficacy for various solid tumor models, confirming its potential utility and versatility in antitumor therapy.
A cleavable amphiphilic peptide (CAP) nanocarrier transforms from self‐assembled nanofibers to spherical nanoparticles (NPs) by loading hydrophobic drugs, and cleavage by the tumor‐specific protease, FAP‐α, resulted in specific and efficient release of the encapsulated drugs at tumor sites. This Transformers‐like drug nanocarrier could disrupt the stromal barrier, and enhance local drug accumulation.
Near-infrared plasmonic nanoparticles demonstrate great potential in disease theranostic applications. Herein a nanoplatform, composed of mesoporous silica-coated gold nanorods (AuNRs), is ...tailor-designed to optimize the photodynamic therapy (PDT) for tumor based on the plasmonic effect. The surface plasmon resonance of AuNRs was fine-tuned to overlap with the exciton absorption of indocyanine green (ICG), a near-infrared photodynamic dye with poor photostability and low quantum yield. Such overlap greatly increases the singlet oxygen yield of incorporated ICG by maximizing the local field enhancement, and protecting the ICG molecules against photodegradation by virtue of the high absorption cross section of the AuNRs. The silica shell strongly increased ICG payload with the additional benefit of enhancing ICG photostability by facilitating the formation of ICG aggregates. As-fabricated AuNR@SiO2–ICG nanoplatform enables trimodal imaging, near-infrared fluorescence from ICG, and two-photon luminescence/photoacoustic tomography from the AuNRs. The integrated strategy significantly improved photodynamic destruction of breast tumor cells and inhibited the growth of orthotopic breast tumors in mice, with mild laser irradiation, through a synergistic effect of PDT and photothermal therapy. Our study highlights the effect of local field enhancement in PDT and demonstrates the importance of systematic design of nanoplatform to greatly enhancing the antitumor efficacy.
•A novel application of Mo/HZSM-5 on improving BTEXN yield was investigated in situ.•The yield of BTEXN from coal pyrolysis was increased remarkably by HZSM-5 and Mo/HZSM-5.•The conditions and ...principle of Mo/HZSM-5 improving BTEXN yield were obtained.
The effect of Mo/HZSM-5 and HZSM-5 on the yield of aromatic hydrocarbons such as BTEXN (benzene, toluene, ethylbenzene, xylene, naphthalene) during Pingshuo Coal flash pyrolysis at different temperatures was analyzed using Py-GC/MS. It shows that both HZSM-5 and Mo/HZSM-5 can remarkably increase the yield of BTEXN. HZSM-5 shows the highest catalytic activity at 900°C, the total BTEXN yield increases from 116ng/mg at 500°C to a maximum of 7000ng/mg at 900°C, and then decreases with further increase of temperature. The maximum yield with HZSM-5 obtained at 900°C is more than three times that without HZSM-5. However, Mo/HZSM-5 has the potential to yield more BTEXN, as the maximum yield of BTEXN is 7020ng/mg at 800°C. The results indicate that Mo has been loaded on the HZSM-5 zeolite as MoO3. As a result, Mo/HZSM-5 can promote the aromatization of olefins and alkanes, dehydroxylation of phenolic compounds, as well as aromatization of CH4. Thus, Mo/HZSM-5 is more suitable for the catalytic conversion of the gaseous products from coal pyrolysis into BTEXN.
Fibrotic stroma, a critical character of pancreatic tumor microenvironment, provides a critical barrier against the penetration and efficacy of various antitumor drugs. Therefore, new strategies are ...urgently needed to alleviate the fibrotic mass and increase the drug perfusion within pancreatic cancer tissue. In our current work, we developed a β-cyclodextrin (β-CD) modified matrix metalloproteinase-2 (MMP-2) responsive liposome, integrating antifibrosis and chemotherapeutic drugs for regulation of pancreatic stellate cells (PSCs), a key source of the fibrosis, and targeted delivery of cytotoxic drugs for pancreatic cancer therapy. These liposomes disassembed into two functional parts upon MMP-2 cleavage at the tumor site. One part was constituted by the β-CDs and the antifibrosis drug pirfenidone, which was kept in the stroma and inhibited the expression of collagen I and TGF-β in PSCs, down-regulating the fibrosis and decreasing the stromal barrier. The other segment, the RGD peptide-modified-liposome loading the chemotherapeutic drug gemcitabine, targeted and killed pancreatic tumor cells. This integrated nanomedicine, showing an increased drug perfusion without any overt side effects, may provide a potential strategy for improvement of the pancreatic cancer therapy.
Phenols from coal pyrolysis are extremely precious chemicals, understanding the factors that influence the amounts and species of phenols during coal pyrolysis is of vital importance. In this study, ...the concentrations of seven species of phenols in the coal extracts were analyzed by GC/MS. Then, the phenols obtained from the pyrolysis of four different coals were characterized by using a flash pyrolysis-GC/MS in-situ. In addition, the amounts of phenols from coal pyrolysis at 400–1000°C with the heating rate of 10°C/ms were calculated. Results show that the total amount of phenols during the pyrolysis of lignite (coal A) was higher than those of long-flame coal (coal B), bituminous coal (coal C), and anthracite (coal D) at 800°C. The main source of phenols is the thermal decomposition of the oxygen-containing structures, particularly aryl ether, rather than the volatilization of the already existing phenols in the raw coal. The formation of phenols, dominated by phenol and cresols, is facilitated during the coal pyrolysis at 600–800°C, otherwise, certain phenols may be decomposed at higher temperatures. Moreover, there is close correlation between the release amount of phenols and the specific surface area of the coal during coal pyrolysis.
•The source of phenols was proposed during coal pyrolysis.•Phenols of lignite is the highest (2316μg/g) during different rank coal pyrolysis.•Most phenols were formed by the thermal cracking of aryl ether at 600–800°C.•Phenols amount is augmented with the increasing SSA during coal pyrolysis.
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