Extensive efforts have been devoted to the development of hybrid structures consisting of biomacromolecules and organic polymers connected through covalent bonds. While the combination of proteins ...and peptides with synthetic macromolecules has been explored in depth, far fewer examples of nucleic acid/polymer hybrids are known. In this Review we give selected examples of this exciting class of materials which can be arranged as linear block copolymer architectures, as side‐chain polymers, or as cross‐linked networks. Emphasis is placed on the fabrication of these materials as well as on their potential applications in nanoscience, diagnostics, and biomedicine.
Nucleic acids have become important building blocks in nanotechnology over the last 30 years. DNA and RNA can sequentially build specific nanostructures, resulting in versatile drug delivery systems. ...Self-assembling amphiphilic nucleic acids, composed of hydrophilic and hydrophobic segments to form micelle structures, have the potential for cancer therapeutics due to their ability to encapsulate hydrophobic agents into their core and position functional groups on the surface. Moreover, DNA or RNA within bio-compatible micelles can function as drugs by themselves. This review introduces and discusses nucleic acid-based spherical micelles from diverse amphiphilic nucleic acids and their applications in cancer therapy.
Induction of antigen-specific immune activation by the maturation of dendritic cells (DCs) is a strategy used for cancer immunotherapy. In this study, we find that FimH, which is an Escherichia coli ...adhesion portion, induces toll-like receptor 4-dependent and myeloid differentiation protein 2-independent DC maturation in mice in vivo. A combined treatment regimen with FimH and antigen promotes antigen-specific immune activation, including proliferation of T cells, production of IFN-γ and TNF-α, and infiltration of effector T cells into tumors, which consequently inhibits tumor growth in mice in vivo against melanoma and carcinoma. In addition, combined therapeutic treatment of anti-PD-L1 antibodies and FimH treatment efficiently inhibits CT26 tumor growth in BALB/c mice. Finally, FimH promotes human peripheral blood DC activation and syngeneic T-cell proliferation and activation. Taken together, these findings demonstrate that FimH can be a useful adjuvant for cancer immunotherapy.
Most previously reported methods for purifying DNA-origami nanostructures rely on agarose-gel electrophoresis (AGE) for separation. Although AGE is routinely used to yield 0.1-1 µg purified DNA ...nanostructures, obtaining >100 µg of purified DNA-origami structure through AGE is typically laborious because of the post-electrophoresis extraction, desalting and concentration steps. Here, we present a readily scalable purification approach utilizing rate-zonal centrifugation, which provides comparable separation resolution as AGE. The DNA nanostructures remain in aqueous solution throughout the purification process. Therefore, the desired products are easily recovered with consistently high yield (40-80%) and without contaminants such as residual agarose gel or DNA intercalating dyes. Seven distinct three-dimensional DNA-origami constructs were purified at the scale of 0.1-100 µg (final yield) per centrifuge tube, showing the versatility of this method. Given the commercially available equipment for gradient mixing and fraction collection, this method should be amenable to automation and further scale up for preparation of larger amounts (e.g. milligram quantities) of DNA nanostructures.
Temperature is one of crucial and integral parts of chemical experiments. Since the properties or shape of the material may change depending on the temperature, the device that measures it plays a ...vital role in an experiment. Such devices commonly used in experiments to this day are unable to perform temperature measurement and data processing simultaneously. Here, we present a low‐price, non‐contact convenient platform capable of solving both problems at the same time, with automatically set different measurement time intervals for each experiment, and shows processed data anywhere real‐time on the Internet. This device can operate within temperature range of −20 and 80 °C with a respectable error range of ±2.5 °C.
An affordable device allows us to simply monitor and immediately display temperature.
Although fucoidan, a well-studied seaweed-extracted polysaccharide, has shown immune stimulatory effects that elicit anticancer immunity, mucosal adjuvant effects via intranasal administration have ...not been studied. In this study, the effect of
-extracted fucoidan (ECF) on the induction of anti-cancer immunity in the lung was examined by intranasal administration. In C57BL/6 and BALB/c mice, intranasal administration of ECF promoted the activation of dendritic cells (DCs), natural killer (NK) cells, and T cells in the mediastinal lymph node (mLN). The ECF-induced NK and T cell activation was mediated by DCs. In addition, intranasal injection with ECF enhanced the anti-PD-L1 antibody-mediated anti-cancer activities against B16 melanoma and CT-26 carcinoma tumor growth in the lungs, which were required cytotoxic T lymphocytes and NK cells. Thus, these data demonstrated that ECF functioned as a mucosal adjuvant that enhanced the immunotherapeutic effect of immune checkpoint inhibitors against metastatic lung cancer.
The ubiquitin-proteasome system is an essential regulator of several cellular pathways involving oncogenes. Deubiquitination negatively regulates target proteins or substrates linked to both ...hereditary and sporadic forms of cancer. The deubiquitinating enzyme ubiquitin-specific protease 14 (USP14) is associated with proteasomes where it trims the ubiquitin chain on the substrate. Here, we found that USP14 is highly expressed in patients with lung cancer. We also demonstrated that USP14 inhibitors (IU1-47 and siRNA-USP14) significantly decreased cell proliferation, migration, and invasion in lung cancer. Remarkably, we found that USP14 negatively regulates lung tumorigenesis not only through apoptosis but also through the autophagy pathway. Our findings suggest that USP14 plays a crucial role in lung tumorigenesis and that USP14 inhibitors are potent drugs in lung cancer treatment.
Abstract We introduce a versatile carrier system for in vitro and in vivo immune stimulation based on soft matter DNA nanoparticles (NPs). The incorporation of lipid-modified nucleotides into DNA ...strands enables the formation of micelles of uniform size. In a single self-assembly step, the micelles can be equipped with immune adjuvant (CpG) motifs and fluorescent probes. The immunological effects of CpG confined at the NP surface were studied in a comprehensive manner in animal experiments. Dose-dependent activation of spleen dendritic cells (DCs) by CpG-conjugated NP was observed, which was accompanied by the pronounced up-regulation of co-stimulatory molecule and cytokine production.
Developing effective drug delivery systems plays an important role in improving the therapeutic outcomes of anticancer agents. In this study, we investigated the potential of a micellar delivery ...system modified with semi-interpenetrating polymer networks (sIPN) to enhance the therapeutic efficacy of doxorubicin (Dox), a widely used chemotherapeutic agent. The sIPN-modified micelles were prepared by loading polymerizable tetraacrylate moiety into the core of sodium dodecyl benzene sulfonate (SDBS) micelles. To evaluate the stability of SDBS-micelle and SDBS-sIPN, we assessed the stability of the micellar structure under critical micelle temperature conditions. The results demonstrated that incorporating sIPN significantly enhanced the structural stability of the micelles, particularly in response to acrylate unit concentrations, leading to the 60 days continuous release of Dox. Furthermore, we examined the ability of SDBS-micelle-Dox and SDBS-sIPN-Dox to induce apoptosis and necrosis in HeLa cells. Annexin V/PI double staining and flow cytometry analysis revealed that SDBS-sIPN-Dox exhibited a sustained release profile of Dox, resulting in a reduced apoptotic response compared to free Dox and SDBS-micelle-Dox in the given time. These findings highlight the potential of the sIPN-modified micellar delivery system as an efficient drug delivery platform, enabling sustained release and minimizing adverse side effects associated with immediate drug release. The sustained release profile achieved through incorporation of sIPN structures holds great promise for improving the therapeutic outcomes of anticancer agents.
Graphical Abstract
This study involved the fabrication of semi-interpenetrating polymer network (sIPN)-stabilized micelles using an FDAapproved surfactant and loading anti-cancer drug inside. The stability of the resulting stabilized micelle and the prolonged release of the drug, doxorubicin, were evaluated. The findings underscore the potential of sIPN-stabilized micelles as an effective drug delivery platform, capable of providing sustained release and improving therapeutic outcomes for anticancer drugs.
Efficient cancer therapy is sought not only for primary tumor treatment but also for the prevention of metastatic cancer growth. Immunotherapy has been shown to prevent cancer metastasis by inducing ...antigen-specific immune responses. Indocyanine green (ICG) has a peak spectral absorption at about 800 nm, which makes it a photothermal reagent for direct treatment of solid tumors by photothermal therapy (PTT). Since PTT alone cannot fully induce antigen-specific immune response for prevention of cancer metastasis, the combination of PTT and immunotherapy has been developed as a new strategy of cancer treatment.
Thermal responsive liposomes (TRL) were synthesized by incorporating ICG into the lipid bilayer and encapsulating the water-soluble immune stimulatory molecule polyinosinic:polycytidylic acid (poly I:C) in the hydrophilic core. The poly I:C- and ICG-containing TRLs (piTRLs) were analyzed according to size, and their photothermal effect was evaluated following laser irradiation at 808 nm. Moreover, the temperature-dependent release of poly I:C was also measured. For cancer therapy, CT-26 (carcinoma) and B16 (melanoma) cells were subcutaneously inoculated to build the 1st transplanted tumor in BALB/c and C57BL/6 mice, respectively. These mice received a 2nd transplantation with the same cancer cells by intravenous inoculation, for evaluation of the anti-metastatic effects of the liposomes after PTT.
Near-infrared (NIR) laser irradiation increased the temperature of piTRLs and effectively released poly I:C from the liposomes. The increased temperature induced a photothermal effect, which promoted cancer cell apoptosis and dissolution of the 1st transplanted tumor. Moreover, the released poly I:C from the piTRL induced activation of dendritic cells (DCs) in tumor draining lymph node (tdLN). Cancer cell apoptosis and DC-activation-mediated cancer antigen-specific immune responses further prevented growth of lung metastatic cancer developed following intravenous transplantation of cancer cells.
These results demonstrated the potential usage of a piTRL with laser irradiation for immuno-photothermal therapy against various types of cancer and their metastases.
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