Tumor Microenvironment Regulation and Cancer Targeting Therapy Based on Nanoparticles.

Although we have made remarkable achievements in cancer awareness and medical technology, there are still tremendous increases in cancer incidence and mortality. However, most anti-tumor strategies, including immunotherapy, show low efficiency in clinical application. More and more evidence suggest that this low efficacy may be closely related to the immunosuppression of the tumor microenvironment (TME). The TME plays a significant role in tumorigenesis, development, and metastasis. Therefore, it is necessary to regulate the TME during antitumor therapy. Several strategies are developing to regulate the TME as inhibiting tumor angiogenesis, reversing tumor associated macrophage (TAM) phenotype, removing T cell immunosuppression, and so on. Among them, nanotechnology shows great potential for delivering regulators into TME, which further enhance the antitumor therapy efficacy. Properly designed nanomaterials can carry regulators and/or therapeutic agents to eligible locations or cells to trigger specific immune response and further kill tumor cells. Specifically, the designed nanoparticles could not only directly reverse the primary TME immunosuppression, but also induce effective systemic immune response, which would prevent niche formation before metastasis and inhibit tumor recurrence. In this review, we summarized the development of nanoparticles (NPs) for anti-cancer therapy, TME regulation, and tumor metastasis inhibition. We also discussed the prospect and potential of nanocarriers for cancer therapy.

Virus-like Particles for TEM Regulation and Antitumor Therapy.

Tumor development and metastasis are intimately associated with the tumor microenvironment (TME), and it is difficult for vector-restricted drugs to act on the TME for long-term cancer immunotherapy. Virus-like particles (VLPs) are nanocage structures self-assembled from nucleic acid free viral proteins. Most VLPs range from 20-200 nm in diameter and can naturally drain into lymph nodes to induce robust humoral immunity. As natural nucleic acid nanocarriers, their surfaces can also be genetically or chemically modified to achieve functions such as TME targeting. This review focuses on the design ideas of VLP as nanocarriers and the progress of their research in regulating TME.

Langmuir-Blodgett Deposition of Cellulose Nanocrystal Surfactants into Ordered Monolayers.

The cellulose nanocrystals (CNCs) are shown to interact with amine-functionalized polyhedral oligomeric silsesquioxane (POSS-NH2) strongly at the water/oil interface, forming the CNC-POSS assemblies, that is, CNC surfactants that decrease the interfacial tension of the water/chloroform greatly. When bringing the CNC aqueous solution and POSS chloroform solution into a Langmuir trough, they form a monolayer of the CNC surfactants. Upon applying a continuous compression, a distinct transition appears in the surface pressure-area curves, and during this transition, the packing of the CNC surfactants in the produced monolayers transits from network-like patterns to ordered alignment.

Ion Interference Therapy of Tumors Based on Inorganic Nanoparticles.

As an essential substance for cell life activities, ions play an important role in controlling cell osmotic pressure balance, intracellular acid-base balance, signal transmission, biocatalysis and so on. The imbalance of ion homeostasis in cells will seriously affect the activities of cells, cause irreversible damage to cells or induce cell death. Therefore, artificially interfering with the ion homeostasis in tumor cells has become a new means to inhibit the proliferation of tumor cells. This treatment is called ion interference therapy (IIT). Although some molecular carriers of ions have been developed for intracellular ion delivery, inorganic nanoparticles are widely used in ion interference therapy because of their higher ion delivery ability and higher biocompatibility compared with molecular carriers. This article reviewed the recent development of IIT based on inorganic nanoparticles and summarized the advantages and disadvantages of this treatment and the challenges of future development, hoping to provide a reference for future research.

Hypoxia-Overcoming Breast-Conserving Treatment by Magnetothermodynamic Implant for a Localized Free-Radical Burst Combined with Hyperthermia.

For the purpose of improving the quality of life and minimizing the psychological morbidity of a mastectomy, breast-conserving treatment (BCT) has become the more preferable choice in breast cancer patients. Meanwhile, tumor hypoxia has been increasingly recognized as a major deleterious factor in cancer therapies. In the current study, a novel, effective, and noninvasive magnetothermodynamic strategy based on an oxygen-independent free-radical burst for hypoxia-overcoming BCT is proposed. Radical precursor (AIPH) and iron oxide nanoparticles (IONPs) are coincorporated within the alginate (ALG) hydrogel, which is formed in situ within the tumor tissue by leveraging the cross-linking effect induced by the local physiological Ca2+ with ALG solution. Inductive heating is mediated by IONPs under AMF exposure, and consequently, regardless of the tumor hypoxia condition, a local free-radical burst is achieved by thermal decomposition of AIPH via AMF responsivity. The combination of magnetic hyperthermia and oxygen-irrelevant free-radical production effectively enhances the in vitro cytotoxic effect and also remarkably inhibits tumor proliferation. This study provides a valuable protocol for an hypoxia-overcoming strategy and also an alternative formulation candidate for noninvasive BCT.

Ferrous ions doped layered double hydroxide: smart 2D nanotheranostic platform with imaging-guided synergistic chemo/photothermal therapy for breast cancer.

Developing simple and efficient nanotheranostic platforms with behavior responsive to the acid microenvironment of a tumor is of great significance for accurate tumor diagnosis and therapy. In this study, a smart 2D nanotheranostic platform has been successfully fabricated by doping functional ferrous ions into as-synthesized MgAl-layered double hydroxide (LDH) with doxurubicin (DOX) loading to form Fe-LDH/DOX NPs, which achieved magnetic resonance imaging (MRI)-guided synergistic chemo/photothermal therapy for breast cancer. The doping of ferrous ions into Fe-LDH/DOX enabled a strong photo-induced heating ability with a high photothermal conversion efficiency of 45.67%, which could be combined with the antitumor drug DOX to achieve the synergistic effect of photothermal therapy (PTT) and chemotherapy for killing tumor cells. Additionally, its in vitro pH-dependent degradation behavior and T2-weighted MRI effect revealed that the as-prepared Fe-LDH/DOX is sensitive to the tumor acid microenvironment. Most importantly, the growth rate of tumors in 4T1 bearing mice could be effectively inhibited after the synergistic treatment of PTT and chemotherapy by Fe-LDH/DOX. These results show that doping functional metal ions into LDH NPs may open a novel approach to fabricating an LDH NP-based nanotheranostics platform with advanced diagnostic and therapeutic performances.

Gold-iron selenide nanocomposites for amplified tumor oxidative stress-augmented photo-radiotherapy.

The radio-resistance of tumor tissues has been considered a great challenge for cancer radiotherapy (RT).The development of nanoparticle (NP)-based radio-sensitizers can enhance the radio-sensitization of tumor tissues while reducing the side effects to surrounding tissues. However, most of the nano-radiosensitizers show increased radiation deposition with a high-Z element but achieve limited enhancement. Herein, we investigated polyethylene glycol (PEG)-modified gold-iron selenide nanocomposites (Au-FeSe2 NCs) for simultaneously enhancing therapeutic effects in multiple ways. In this study, the high-Z element Au (Z = 79) endows Au-FeSe2 NCs with enhanced X-ray deposition and thus causes more DNA damage. On the other hand, Au-FeSe2 exhibits the ability to produce reactive oxygen species (ROS) by catalyzing endogenous hydrogen peroxide in tumor sites as well as improve the hydrogen peroxide level during ionizing irradiation. Finally, combined with photothermal therapy (PTT), Au-FeSe2 NCs could exhibit a remarkable RT/PTT synergistic effect on tumor treatment.

Tannic acid-based metal phenolic networks for bio-applications: a review.

Tannic acid (TA), a large polyphenolic molecule, has long been known for use in food additives, antioxidants, bio-sorbents, animal feed and adhesives due to its intrinsic properties such as antioxidation, metal chelation, and polymerization. Recently, there has been a renewed interest in fabricating engineered advanced materials with TA modification for novel bio-applications. The modification process involves various interactions/reactions based on its diverse chemical structure, contributed by abundant aromatic rings and hydroxyl groups. In addition, the obtained composites are endowed with retained TA activity and novel enhanced properties. Therefore, the aim of this review is to highlight the recent biomedical application of TA-based metal phenolic networks (TA-MPNs) by focusing on their intrinsic properties and the endowed ability for novel engineered functional composites. The potential contributions of TA-MPNs in "Tumor Theranostics", "Anti-Bacterial Ability", "Wound Repair for Skin Regeneration" and "Bone Tissue Regeneration Applications" are summarized in this paper.

Galvanic replacement reaction for in situ fabrication of litchi-shaped heterogeneous liquid metal-Au nano-composite for radio-photothermal cancer therapy.

With tremendous research advances in biomedical application, liquid metals (LM) also offer fantastic chemistry for synthesis of novel nano-composites. Herein, as a pioneering trial, litchi-shaped heterogeneous eutectic gallium indium-Au nanoparticles (EGaIn-Au NPs), served as effective radiosensitizer and photothermal agent for radio-photothermal cancer therapy, have been successfully prepared using in situ interfacial galvanic replacement reaction. The enhanced photothermal conversion efficiency and boosted radio-sensitization effect could be achieved with the reduction of Au nanodots onto the eutectic gallium indium (EGaIn) NPs surface. Most importantly, the growth of tumor could be effectively inhibited under the combined radio-photothermal therapy mediated by EGaIn-Au NPs. Inspired by this approach, in situ interfacial galvanic replacement reaction may open a novel strategy to fabricate LM-based nano-composite with advanced multi-functionalities.

Dihydroartemisinin loaded layered double hydroxide nanocomposites for tumor specific photothermal-chemodynamic therapy.

With the inspiration to develop new cancer nanotherapeutics by repurposing old drugs, in the current study, a novel two dimensional nanomedicine namely Mn doped, dihydroartemisinin (DHA) loaded layered double hydroxide (MnMgFe-LDH/DHA) with peroxide self-supplying properties for enhanced photothermal-chemodynamic therapy was proposed. Such nanostructures could be synthesized by a simple coprecipitation method, and the as-prepared MnMgFe-LDH/DHA exhibits excellent photothermal properties with a photothermal conversion efficiency up to 10.7%. Besides, the in situ reaction between the released DHA and Fe2+/Mn2+ produced by the degradation of LDH can lead to a burst of intracellular reactive oxygen species (ROS) by Fenton-like reactions. Furthermore, the in vivo experiments demonstrate that MnMgFe-LDH/DHA exhibits a remarkable chemodynamic/photothermal therapy (CDT/PTT) synergistic effect on tumor treatment with negligible damage to normal tissues. Finally, this research provides a smart strategy to construct a DHA repurposing nanomedicine for tumor specific treatment.

3D Printing of Conductive Tissue Engineering Scaffolds Containing Polypyrrole Nanoparticles with Different Morphologies and Concentrations.

Inspired by electrically active tissues, conductive materials have been extensively developed for electrically active tissue engineering scaffolds. In addition to excellent conductivity, nanocomposite conductive materials can also provide nanoscale structure similar to the natural extracellular microenvironment. Recently, the combination of three-dimensional (3D) printing and nanotechnology has opened up a new era of conductive tissue engineering scaffolds exhibiting optimized properties and multifunctionality. Furthermore, in the case of two-dimensional (2D) conductive film scaffolds such as periosteum, nerve membrane, skin repair, etc., the traditional preparation process, such as solvent casting, produces 2D films with defects of unequal bubbles and thickness frequently. In this study, poly-l-lactide (PLLA) conductive scaffolds incorporated with polypyrrole (PPy) nanoparticles, which have multiscale structure similar to natural tissue, were prepared by combining extrusion-based low-temperature deposition 3D printing with freeze-drying. Furthermore, we creatively integrated the advantages of 3D printing and solvent casting and successfully developed a 2D conductive film scaffold with no bubbles, uniform thickness, and good structural stability. Subsequently, the effects of concentration and morphology of PPy nanoparticles on electrical properties and mechanical properties of 3D conductive scaffolds and 2D conductive films scaffolds have been studied, which provided a new idea for the design of both 2D and 3D electroactive tissue engineering scaffolds.

[Research Progress in Analytical Technology for Heavy Metals in Atmospheric Particles].

Atmospheric particles have become the primary atmospheric pollutions, of which the heavy metals, owing to non-degradability and hysteresis, a serious threat to human life and natural environment, have become a hot research issue currently. The analytical methods of heavy metals in atmospheric particles are summarized in the present review, including atomic absorption spectrometry, inductively coupled plasma atomic emission spectrometry, inductively coupled plasma mass spectrometry, neutron activation analysis, fluorescence spectrometry, glow discharge atomic emission spectrometry, microwave plasma atomic emission spectrometry, and laser induced breakdown spectroscopy, and some proposals are tried to make for improving the shortcomings of these technologies: continuum source Atomic absorption spectrometry for simultaneously measuring multi-elements, atomic emission spectrometry for direct determination of particulates, high resolution laser ablation inductively coupled plasma mass spectrometry for determination of solid samples, low scattering synchrotron fluorescence spectrum for determination of atmospheric particulate matter and k0 neutron activation analysis for determination of radioactive elements in the troposphere Analysis techniques of heavy metals in atmospheric particulate matter are promoted to develop toward being real-time, fast, low- detection-limit, direct-measurement and simple-operation due to the spatial and temporal distribution difference of the heavy metals in atmospheric particles and human requirement for improvement of ambient air quality as well as rapid development of modern instrument science and technology.