Nuclear delivery and accumulation are very important for many anticancer drugs that interact with DNA or its associated enzymes in the nucleus. However, it is very difficult for neutrally and negatively charged anticancer drugs such as 10-hydroxycamptothecine (HCPT). Here we report a simple strategy to construct supramolecular nanomedicines for nuclear delivery of dual synergistic anticancer drugs. Our strategy utilizes the coassembly of a negatively charged HCPT-peptide amphiphile and the positively charged cisplatin. The resulting nanomaterials behave as the "Trojan Horse" that transported soldiers (anticancer drugs) across the walls of the castle (cell and nucleus membranes). Therefore, they show improved inhibition capacity to cancer cells including the drug resistant cancer cell and promote the synergistic tumor suppression property in vivo. We envision that our strategy of constructing nanomaterials by metal chelation would offer new opportunities to develop nanomedicines for combination chemotherapy.
Promising vaccine adjuvants of self‐assembling peptide hydrogels for protein ovalbumin (OVA) are introduced in this study. The hydrogels are formed by the enzyme of phosphatase, and the vaccine adjuvant potency of both l‐ and d‐peptide hydrogels is evaluated. The results indicate that, compared with the clinically used alum adjuvant, both l‐ and d‐peptide hydrogels can increase the IgG production of OVA for about 1.3 and 3.8 times, respectively. Both gels can enhance antigen uptake and induce dendritic cell maturation, and promote and prolong accumulation of antigen in lymph node, as well as evoke germinal center formation. However, the d‐peptide hydrogel with OVA exhibits a slightly more efficient accumulation of OVA in the lymph nodes and seems preventing tumor growth more significantly than its l‐counterpart. With the good biocompatibility and degradability of peptide hydrogels, the hydrogels described in this study have big potential for the production of protein vaccines for immunotherapy against different diseases.
Nano-materials formed by the self-assembly of small molecules are very promising for drug delivery, regenerative medicine, and detection of important analytes due to their unique properties, such as self-assembled multivalency, biocompatibility, and fast response to external stimuli. This tutorial review focuses on their applications in detection of important analytes. Self-assembling small molecules can show fast response to external stimuli. Therefore, the gel-sol/sol-gel phase transitions of supramolecular hydrogels that can be easily identified by naked eyes have been applied for the detection of enzymes and enzyme-involving analytes. The supramolecular hydrogels can also provide semi-wet environments that can retain the activity of enzymes and recognition properties of molecular probes. Thus, they provide good platforms for the detection of many biologically and environmentally important analytes. Besides, self-assembling small molecules show big differences in fluorescence or the F-NMR signal between their self-assembled and un-assembled stages. Such small molecules can be rationally designed through the integration of fluorescent dyes or fluorine containing molecules in the self-assembling small molecules. Therefore, extensive recent research efforts have been made to explore their detection applications based on the dis-assembly triggered fluorescence/F-NMR signal turn on or the self-assembly/aggregation induced fluorescence turn on. We believe that the research efforts made to this field will ultimately lead to the development of useful nano-materials for detection applications.
An ideal radiosensitizer holding an enhanced tumor retention can play an incredible role in enhancing tumor radiotherapy. Herein, a strategy of acid‐triggered aggregation of small‐sized gold nanoparticles (GNPs) system within tumor is proposed and the resulting GNPs aggregates are applied as a radiosensitizer in vitro and in vivo. The GNPs system with the acid‐triggered aggregation achieves an enhanced GNPs accumulation and retention in cancer cells and tumors in the form of the resulted GNPs aggregates. As a consequence, the radiosensitization effect shows significant improvement in cancer radiotherapy, which is shown in the studies of DNA breakage and the comet assay, and the sensitizer enhancement ratio (SER) value of the GNPs system (1.730) with MCF‐7 cancer cells is much larger than that of the single GNPs (1.16). In vivo antitumor studies reveal that the GNPs system also enhances the sensitivity of MCF‐7 tumor xenograft to radiotherapy. Furthermore, the GNPs aggregates improve the signal of small GNPs in vivo photoacoustic imaging. This study provides a new strategy and insights into fabricating nanoaggregates to magnify the radiosensitive efficiency of nanosystems in cancer radiotherapy.
Chemo-photodynamic combination therapy has been received widespread attention in cancer treatment due to its excellent characteristics, such as reducing the adverse side effects of chemo-drugs and improving the therapeutic effects for various cancers. In this study, RGD and DOX was conjugated to PEG by thiol-ene addition and Schiff's base reaction, respectively, to prepare the targeted and pH-sensitive antitumor prodrug nanoparticles (RGD-PEG-DOX NPs, RGD-NPs). Subsequently, the photosensitizer chlorin e6 (Ce6) was encapsulated into RGD-NPs, thus obtaining a simple and efficient chemo-photodynamic combination platform (RGD-PEG-DOX/Ce6 NPs, RGD-NPs/Ce6). This nanoparticle possessed high drug loading property of both the chemo-drug and photosensitizer and could simultaneously release them under the mild acidic microenvironment of cancer cells, which was expected to realize the synchronization therapy of chemotherapy and photodynamic therapy (PDT). Compared with free DOX and Ce6, RGD-NPs/Ce6 could significantly improve the cellular uptake capacities of DOX and Ce6, resulting in the increased contents of ROS in cancer cells and effective cytotoxicity for tumor cells (MDA-MB-231 cells and MCF-7 cells) upon a laser radiation. The in vivo experiment showed that RGD-NPs/Ce6 displayed superior tumor targeting, accumulation, and retention ability than the other groups (free DOX, free Ce6 and NPs/Ce6), and thus significantly enhancing the antitumor effect in vivo with a laser radiation. In addition, the cardiotoxicity induced by DOX was thoroughly wiped out after being loaded and delivered by the nanoparticles according to the pathological analysis. Therefore, the targeted chemo-photodynamic combination therapeutic platform may be a promising candidate for enhanced cancer therapy.
We demonstrate that the incorporation of one or two amino acids of phenylalanine (F) or 4-fluoro phenylalanine ((f)F) will greatly lower the background fluorescence intensities of conventional quenched probes with quenchers. This enhanced quenching effect was due to the synergetic effect of the aggregation caused quenching and the presence of a quencher. Such strategy will not greatly affect the enzyme recognition properties to the probes. We also demonstrated that our self-assembled nanoprobe with the enhanced quenching effect showed a better performance in cells for the detection of cell apoptosis than the unassembled probes. Our study demonstrates that using molecular self-assembly can optimize and improve the performance of molecular probes and it provides a simple but very useful strategy to boost the signal-to-noise ratios of fluorescence probes.
Purpose The titanium mesh cage (TMC) is a typical metal cage device which has been widely used in cervical reconstruction for decades. Nano-hydroxyapatite/polyamide-66 (n-HA/PA66) cage is a novel biomimetic non-metal cage device growing in popularity in many medical centres in recent years. There has been no comparison of the efficacy between these two anterior reconstructing cages. The purpose of this study was to compare the radiographic and clinical outcomes of these two different devices. Methods Sixty-seven eligible patients with single-level ACCF using TMC or n-HA/PA66 cage for cervical degenerative diseases, with four-year minimum follow-up, were included in this prospective non-randomised comparative study. Their radiographic (cage subsidence, fusion status, segmental sagittal alignment [SSA]) and clinical (VAS and JOA scales) data before surgery and at each follow-up was recorded completely. Results The fusion rate of the n-HA/PA66 group was higher than TMC at one year after surgery (94 % vs. 84 %) though their finial fusion rates were similar (97 % vs. 94 %). Finial n-HA/PA66 cage subsidence was 1.5 mm with 6 % of severe subsidence over three millimetres, which was significantly lower than the respective 2.9 mm and 22 % of TMC (P <0.0001). Lastly, SSA, VAS and JOA in TMC group were worse than in the n-HA/PA66 group (P =0.235, 0.034 and 0.007, respectively). ConclusionsThe n-HA/PA66 cage is associated with earlier radiographic fusion, less subsidence and better clinical results than TMC within four years after one-level ACCF. With the added benefit of radiolucency, the n-HA/PA66 cage may be superior to TMC in anterior cervical construction.
CDA may result in better mid- to long-term functional recovery and a lower rate of subsequent surgical procedures than ACDF would. A review of the literature showed that only an insufficient number of studies had investigated adjacent segment disease; therefore, it is mandatory that adequate future research should focus in this direction.
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