Antibiotic is one of the greatest discoveries in human history. It has drastically promoted modern medicine and extended the average human lifespan. However, antibiotic resistance has become a global ...crisis today and the development of novel antibiotics is highly demanded. The traditional antibiotics not only kill the pathogen but also damage the resident microbiome in the human body, thus promoting antibiotic resistance and elevating the risk of patients for new infection. Here, we fabricated an activable metal-phenolic network nano-antibiotics (PEG-P18-Ag NPs) that can be selectively activated on the site of infection, thus presumably avoiding their impacts on the resident microbiome. We showed that PEG-P18-Ag NPs
per se
do not have any antibacterial activity. However, upon activation by the ultrasound, they triggered the generation of reactive oxygen species. Consequently, PEG-P18-Ag NPs remarkably killed various multi-drug resistant bacteria and established biofilms
in vitro
and
in vivo
. By RNA sequencing, we revealed that activated PEG-P18-Ag NPs produced a profound damaging effect on the bacteria. Collectively, we provided a novel approach for the new generation of antibiotics that selectively target infected bacteria.
Intratumoral CD8+ T cells are crucial for effective cancer immunotherapy, but an immunosuppressive tumor microenvironment (TME) contributes to dysfunction and insufficient infiltration. Drug ...repurposing has successfully led to new discoveries among existing clinical drugs for use as immune modulators to ameliorate immunosuppression in TME and reactivate T‐cell‐mediated antitumor immunity. However, due to suboptimal tumor bioavailability, the full potential of immunomodulatory effects of these old drugs has not been realized. The self‐degradable PMI nanogels carrying two repurposed immune modulators, imiquimod (Imi) and metformin (Met), are reported for TME‐responsive drug release. It remodels the TME through the following aspects: 1) promoting dendritic cells maturation, 2) repolarizing M2‐like tumor‐associated macrophages, and 3) downregulating PD‐L1 expression. Ultimately, PMI nanogels reshaped the immunosuppressive TME and efficiently promote CD8+ T cell infiltration and activation. These results support that PMI nanogels can potentially be an effective combination drug for enhancing the antitumor immune response of anti‐PD‐1 antibodies.
Self‐degradable nanogels with tumor microenvironment (TME)‐responsiveness exhibit unique properties of targeted and rapid drug release, which can revert the immunosuppressive TME to the anti‐tumor state. And the improved immunosuppressive TME can reactivate T‐cell‐mediated antitumor immunity by promoting CD8+ T cell infiltration and activation, which enhances the anticancer activity of current cancer immunotherapy.
Monodisperse rare earth (RE) fluoride colloidal nanocrystals (NCs) including REF(3) (RE = La, Pr, Nd), NaREF(4) (RE = Sm-Ho, Y) and Na(5)RE(9)F(32) (RE = Er, Yb, Lu) have been successfully ...synthesized by a facile one-step method using oleic acid as surfactant and 1-octadecene as solvent. The phase, morphology, size, and photoluminescence properties of as-synthesized NCs were well investigated by X-ray diffraction (XRD), transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HRTEM), Fourier transform infrared spectroscopy (FT-IR), and photoluminescence (PL) spectra. The results reveal that the as-synthesized NCs consist of monodisperse colloidal NCs with narrow size distribution, which can easily disperse in non-polar cyclohexane solvent. The as-prepared NCs exhibit a rich variety of morphologies and different crystal phases (hexagonal or cubic), which may be related to the inherent natures of different rare earth ions. The possible formation mechanism of NCs with diverse architectures has been presented. In addition, representative Yb/Er, Yb/Tm, or Yb/Ho co-doped NaGdF(4) and Na(5)Lu(9)F(32) NCs exhibit intensive multicolor up-conversion (UC) luminescence under a single 980 nm NIR excitation, displaying potential applications in bioimaging and therapy. Moreover, transparent and UC fluorescent NCs-polydimethylsiloxane (PDMS) composites with regular dimensions were also prepared by an in situ polymerization route.
Nanovehicles can efficiently carry and deliver anticancer agents to tumour sites. Compared with normal tissue, the tumour microenvironment has some unique properties, such as vascular abnormalities, ...hypoxia and acidic pH. There are many types of cells, including tumour cells, macrophages, immune and fibroblast cells, fed by defective blood vessels in the solid tumour. Exploiting the tumour microenvironment can benefit the design of nanoparticles for enhanced therapeutic effectiveness. In this review article, we summarized the recent progress in various nanoformulations for cancer therapy, with a special emphasis on tumour microenvironment stimuli-responsive ones. Numerous tumour microenvironment modulation strategies with promising cancer therapeutic efficacy have also been highlighted. Future challenges and opportunities of design consideration are also discussed in detail. We believe that these tumour microenvironment modulation strategies offer a good chance for the practical translation of nanoparticle formulas into clinic.
Exploiting the tumour microenvironment can benefit the design of nanomaterials for enhanced therapeutic effectiveness.
Summary
Aminoglycosides are one of the oldest classes of antimicrobials that are being used in current clinical practice, especially on multi‐drug resistant Gram‐negative pathogenic bacteria. ...However, the serious side effects at high dosage such as ototoxicity, neuropathy and nephrotoxicity limit their applications in clinical practice. Approaches that potentiate aminoglycoside killing could lower down their effective concentrations to a non‐toxic dosage for clinical treatment. In this research, we screened a compound library and identified sanguinarine that acts synergistically with various aminoglycosides. By checkerboard and dynamical killing assay, we found that sanguinarine effectively potentiated aminoglycoside killing on diverse bacterial pathogens, including Escherichia coli, Acinetobacter baumannii, Klebsiella pneumonia and Pseudomonas aeruginosa. The mechanistic studies showed an elevated intracellular ROS and DNA oxidative level in the bacterial cells treated by a combination of sanguinarine with aminoglycosides. Furthermore, an enhanced level of sanguinarine was observed in bacteria in the presence of aminoglycosides, suggesting that aminoglycosides promote the uptake of sanguinarine. Importantly, sanguinarine was shown to promote the elimination of persister cells and established biofilm cells both in vivo and in vitro. Our study provides a novel insight for approaches to lower down the clinical dosages of aminoglycosides.
Aminoglycosides primarily interact with the bacterial ribosomes and result in protein misfolding and ROS production. Insertion of abnormal proteins into the cell membrane increases the membrane permeability and leads to enhanced uptake of sanguinarine. The sanguinarine acts synergistically with aminoglycoside to generate high level of ROS and results in bacterial death.
Clearly delineating the tumor foci based on multimodal imaging techniques and precisely guiding the minimally invasive therapy are pivotal to completely remove tumors, especially for early ...micro-tumor lesions. Nevertheless, single-mode imaging techniques are difficult to accurately visualize the tumor region, and the mono-therapeutic strategy is hardly a complete removal of the tumor. In this study, we prepare a biodegradable amphiphilic polymer containing poly(aspartic acid). It is further self-assembled with Bi3+ and ultrasmall Fe3O4 to form a multifunctional nanocomplex (Bi/Fe3O4@P3), which served as a CT/MRI dual-imaging contrast agent and enhanced the photothermal/chemodynamic synergistic therapy. In addition, to enhance the photothermal efficiency, the thermal stress also elevated the level of intracellular H2O2, which would facilitate the Fenton reaction between Bi3+/Fe2+ and H2O2 and improve the chemodynamic therapy (CDT) efficacy. Particularly, Bi/Fe3O4@P3 would concurrently deplete the abundant intracellular GSH through the coordination of Bi3+ with GSH to further potentiate the PTT/CDT synergistic tumoricidal efficacy. Therefore, our study was expected to provide a promising theranostic nano-agent and potential comprehensive therapeutic strategy for microtumors.
Combination therapy with multiple chemotherapeutic agents is the main approach for cancer treatment in the clinic. Polyphenol-based materials are found in our diet, demonstrate good biocompatibility, ...and prevent numerous diseases. In this study, we encapsulate two drugs in a single polyphenol-based polymer with Fe
3+
or Mn
2+
ions as the cross-linker for cancer therapy. The combination index of two drugs is an essential parameter to evaluate drug combinations. The amphiphilic polymer poly(ethylene glycol)-
block
-polydopamine (PEG-PDA) was prepared by RAFT polymerization. The nanoparticles were prepared
via
self-assembly with Fe
3+
or Mn
2+
ions. Both doxorubicin (DOX) and simvastatin (SV) were encapsulated in the core of the nanoparticles. The cell viability and combination index were evaluated
in vitro
. The tumor accumulation of the nanoparticles was investigated by positron-emission tomography (PET) and magnetic resonance (MR) imaging. The as-prepared nanoparticles exhibited high drug loading capacity. The drug loaded nanoparticles could kill cancer cells effectively with a combination index <1. Both PET and MRI revealed that the nanoparticles showed long blood circulation time and high tumor accumulation. The nanoparticles could inhibit tumor inhibition
via
intravenous injection of nanoparticles. The polyphenol-based nanoplatform may serve as a promising theranostic candidate for clinical application.
A smart nanoplatform with doxorubicin (DOX) and simvastatin (SV) was fabricated by encapsulating both drugs in a polyphenol-based polymer for chemotherapy and MRI/PET imaging.
Nanomedicine integrates different functional materials to realize the customization of carriers, aiming at increasing the cancer therapeutic efficacy and reducing the off‐target toxicity. However, ...efforts on developing new drug carriers that combine precise diagnosis and accurate treatment have met challenges of uneasy synthesis, poor stability, difficult metabolism, and high cytotoxicity. Metal‐phenolic networks (MPNs), making use of the coordination between phenolic ligands and metal ions, have emerged as promising candidates for nanomedicine, most notably through the service as multifunctional theranostic nanoplatforms. MPNs present unique properties, such as rapid preparation, negligible cytotoxicity, and pH responsiveness. Additionally, MPNs can be further modified and functionalized to meet specific application requirements. Here, the classification of polyphenols is first summarized, followed by the introduction of the properties and preparation strategies of MPNs. Then, their recent advances in biomedical sciences including bioimaging and anti‐tumor therapies are highlighted. Finally, the main limitations, challenges, and outlooks regarding MPNs are raised and discussed.
Metal‐phenolic networks (MPNs) are promising nanoplatforms for biomedical application due to the fast, simple, and stable coordination between metal ions and phenolic ligands. A comprehensive introduction of polyphenols, including natural polyphenol and artificial polyphenol derivatives, and the fabrication and properties of MPNs are provided. Their recent advances and problems in the biomedical field are also discussed.
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•Biomedical applications of metal-organic frameworks (MOFs) are reviewed.•Development, synthesis, and modification of MOFs are introduced briefly.•MOFs serve as nanoplatform for ...bioimaging including CT, MRI, PET, and optical imaging.•MOFs-based synergistic cancer chemotherapy provides superadditive antitumor effect.
Metal-organic frameworks (MOFs) are a novel class of porous materials made from metal ions and organic ligands, and have been widely explored as multifunctional nanoplatforms. MOFs present unique physicochemical characteristics, such as large surface area, tunable size and structure, and easy modification, thereby making them promising candidates for drug delivery, biomedical imaging, and therapeutic applications. Simultaneous utilization of organic linkers and various metal ions as the coordination centers provides possibility to generate multifunctional MOFs with a number of advantages. This feature article summarizes the development and modification of MOFs with emphasis on the recent progress of chemotherapy-based synergistic combination therapy and bioimaging techinques, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and optical imaging (OI). Future prospects and challenges of MOFs in the research of translational medicine are also discussed.
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