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.
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.
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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Despite tremendous advances in gas therapy, there are major concerns about the inevitable concentration of toxicity and the ability to perform real-time tracking of drug delivery. ...Second near-infrared (NIR-II) window absorbing nanoplatforms hold great promise for precision medicine because of their excellent tissue penetration of light and non-invasive nature. In this study, we engineered an NIR-II laser-activated theranostic agent (named CP-bF@PEG) that was composed of amphiphilic polymers (Pluronic F127, with polyethylene glycol, PEG, moieties) coated with an NIR-II-absorbing conjugated polymer (PTTBBT, CP) and nitric oxide (NO) donor (benzofuroxan, bF), which served as an NIR-II photothermal inducer and NO nanogenerator. Under deep tissue penetration of NIR-II laser irradiation, CP-bF@PEG was found to possess fluorescence imaging ability to accurately identify tumor and excellent photothermal effect. Moreover, CP-bF@PEG could generate NO via glutathione activation in the tumor microenvironment in a controllable manner. This NIR-II-absorbing polymer for high-contrast NIR-II fluorescence imaging-guided precision photothermal therapy achieved synergistic effects with NO therapy, as evidenced by pronounced tumor therapeutic efficacy and few side effects. This nanotheranostic agent is a highly promising candidate for high-contrast NIR-II imaging-guided precision photothermal therapy combined with gas therapy against cancer.
Polyphenols, the phenolic hydroxyl group‐containing organic molecules, are widely found in natural plants and have shown beneficial effects on human health. Recently, polyphenol‐containing ...nanoparticles have attracted extensive research attention due to their antioxidation property, anticancer activity, and universal adherent affinity, and thus have shown great promise in the preparation, stabilization, and modification of multifunctional nanoassemblies for bioimaging, therapeutic delivery, and other biomedical applications. Additionally, the metal−polyphenol networks, formed by the coordination interactions between polyphenols and metal ions, have been used to prepare an important class of polyphenol‐containing nanoparticles for surface modification, bioimaging, drug delivery, and disease treatments. By focusing on the interactions between polyphenols and different materials (e.g., metal ions, inorganic materials, polymers, proteins, and nucleic acids), a comprehensive review on the synthesis and properties of the polyphenol‐containing nanoparticles is provided. Moreover, the remarkable versatility of polyphenol‐containing nanoparticles in different biomedical applications, including biodetection, multimodal bioimaging, protein and gene delivery, bone repair, antibiosis, and cancer theranostics is also demonstrated. Finally, the challenges faced by future research regarding the polyphenol‐containing nanoparticles are discussed.
The synthesis, properties, and biomedical applications of polyphenol‐containing nanomaterials are comprehensively reviewed. The problems in the current polyphenol‐based nanosystems and the future research directions in this field are also discussed.
Recently, lanthanide nanoparticles have aroused widespread interest in cancer theranostics by virtue of their excellent photoresponsive performance in deep‐seated tumors. The abundant ladder‐like ...energy levels, controllable emission profiles, and unique photoluminescence properties make lanthanide nanoparticles highly efficient for deep skin‐penetration of near‐infrared (NIR) light, concentrating light energy in tumors with negligible scattering and minimal autofluorescence from biological tissues. High‐Z radio‐sensitization of lanthanide elements endows lanthanide nanoparticles with a high X‐ray attenuation coefficient, making them effective nanoprobes for X‐ray‐excited bioimaging and synchronous radiotherapy‐related treatments. In this review, comprehensive progressions including the synthesis, structural characteristics of lanthanide nanoparticles, and distinct optical excitation mechanisms with NIR and X‐ray triggers, are summarized. Advances in NIR‐excited and X‐ray‐triggered cancer imaging methods and therapies are described in detail, wherein NIR‐induced luminescence from upconversion nanoparticles and downconversion nanoparticles are introduced separately based on some typical sensitization. Finally, the challenges and opportunities of lanthanide nanoparticles as light‐triggered cancer theranostic candidates are discussed, whose translation from bench to bedside still has a long journey to go.
This review summarizes and discusses the on‐going efforts in optimizing lanthanide nanoparticles to respond to high skin‐penetration near‐infrared (NIR) and X‐ray stimuli, achieving high‐resolution imaging and precise spatiotemporal treatment of deep‐seated/untouchable tumors. Concurrently, orientations from basic concepts, distinct optical conversion mechanisms, to practical merits of NIR/X‐ray‐excited lanthanide nanoparticles have been introduced to facilitate the comprehensive understanding of deep‐seated tumor treatment.
Nanomedicine has revolutionized cancer therapeutic strategies but has not completely changed the outcomes of tricky tumors that evolve a sophisticated immunosuppressive tumor microenvironment (TME) ...such as acidification. Here, a metal-phenolic network-based nanocomplex embedded with lactate oxidase (LOX) and a mitochondrial respiration inhibitor atovaquone (ATO) was constructed for immunosuppressive TME remodeling and sonodynamic therapy (SDT). In this nanocomplex, the sonosensitizer chlorin e6-conjugated polyphenol derivative can induce the generation of tumor lethal reactive oxygen species upon ultrasound irradiation. LOX served as a catalyst for intracellular lactic acid exhaustion, and ATO led to mitochondrial dysfunction to decrease oxygen consumption. This nanocomplex reversed the tumor immunosuppressive status by alleviating tumor hypoxia and acidic TME, achieving the characteristic enhancement of SDT and the inhibition of tumor proliferation and metastasis.
To integrate photodynamic therapy (PDT) with photothermal therapy (PTT) and chemotherapy for enhanced antitumor efficiency, we developed a mild and rational route to synthesize novel multifunctional ...GdOF:Ln@SiO2 (Ln = 10%Yb/1%Er/4%Mn) mesoporous capsules using strong up-conversion luminescent (UCL) GdOF:Ln as cores and mesoporous silica layer as shells, followed by modification with varied functional groups onto the framework. It was found that due to the codoped Yb/Er/Mn in GdOF, the markedly enhanced red emission can efficiently transfer energy to the conjugated PDT agent (ZnPc) which produces high singlet oxygen, and the incorporated carbon dots outside the shell can generate obvious thermal effect under 980 nm laser irradiation and also prevent the premature leaking of ZnPc. Simultaneously, the as-produced thermal effect can obviously enhance the doxorubicin (DOX) release, which greatly improves the chemotherapy, resulting in a synergistic therapeutic effect. The system exhibits drastically enhanced therapeutic efficiency against tumor growth, as demonstrated both in vitro and in vivo. Especially, the doped rare earth ions in the host endow the material with excellent UCL imaging, magnetic resonance imaging (MRI), and computed tomography (CT) imaging properties, thus realizing the target of multimodal imaging guided multiple therapies.
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
or Mn
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
or Mn
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.
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