Intermittent Fasting Primes the Tumor Microenvironment and Improves Nanomedicine Delivery in Hepatocellular Carcinoma

Fasting has many health benefits, including reduced chemotherapy toxicity and improved efficacy. It is unclear how fasting affects the tumor microenvironment (TME) and tumor-targeted drug delivery. Here the effects of intermittent (IF) and short-term (STF) fasting are investigated on tumor growth, TME composition, and liposome delivery in allogeneic hepatocellular carcinoma (HCC) mouse models. To this end, mice are inoculated either subcutaneously or intrahepatically with Hep-55.1C cells and subjected to IF for 24 d or to STF for 1 d. IF but not STF significantly slows down tumor growth. IF increases tumor vascularization and decreases collagen density, resulting in improved liposome delivery. In vitro, fasting furthermore promotes the tumor cell uptake of liposomes. These results demonstrate that IF shapes the TME in HCC towards enhanced drug delivery. Finally, when combining IF with liposomal doxorubicin treatment, the antitumor efficacy of nanochemotherapy is found to be increased, while systemic side effects are reduced. Altogether, these findings exemplify that the beneficial effects of fasting on anticancer therapy outcomes go beyond modulating metabolism at the molecular level.     

Pd Nanosheet‐Covered Hollow Mesoporous Silica Nanoparticles as a Platform for the Chemo‐Photothermal Treatment of Cancer Cells

A versatile system combining chemotherapy with photothermal therapy for cancer cells using Pd nanosheet‐covered hollow mesoporous silica nanoparticles is reported. While the hollow mesoporous silica core can be used to load anticancer drugs (i.e., doxorubicin) for chemotherapy, the Pd nanosheets on the surface of particles can convert NIR light into heat for photothermal therapy. More importantly, the loading of Pd nanosheets on hollow mesoporous silica nanospheres can dramatically increase the amount of cellular internalization of the Pd nanosheets: almost 11 times higher than the unloaded Pd nanosheets. The as‐prepared nanocomposites efficiently deliver both drugs and heat to cancer cells to improve the therapeutic efficiency with minimal side effects. Compared with chemotherapy or photothermal therapy alone, the combination of chemotherapy and phototherapy can significantly improve the therapeutic efficacy, exhibiting a synergistic effect.     

Nanoparticle Conjugation of Ginsenoside Rg3 Inhibits Hepatocellular Carcinoma Development and Metastasis

Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death worldwide. The prognosis of HCC remains very poor; thus, an effective treatment remains urgent. Herein, a type of nanomedicine is developed by conjugating Fe@Fe₃O₄ nanoparticles with ginsenoside Rg3 (NpRg3), which achieves an excellent coupling effect. In the dimethylnitrosamine‐induced HCC model, NpRg3 application significantly prolongs the survival of HCC mice. Further research indicates that NpRg3 application significantly inhibits HCC development and eliminates HCC metastasis to the lung. Notably, NpRg3 application delays HCC‐induced ileocecal morphology and gut microbial alterations more than 12 weeks during HCC progression. NpRg3 administration elevates the abundance of Bacteroidetes and Verrucomicrobia, but decreases Firmicutes. Twenty‐nine predicted microbial gene functions are enriched, while seven gene functions are reduced after NpRg3 administration. Moreover, the metabolomics profile presents a significant progression during HCC development, but NpRg3 administration corrects tumor‐dominant metabolomics. NpRg3 administration decreases 3‐indolepropionic acid and urea, but elevates free fatty acids. Importantly, NpRg3 application remodels the unbalanced correlation networks between gut microbiota and metabolism during HCC therapy. In conclusion, nanoparticle conjugation of ginsenoside Rg3 inhibits HCC development and metastasis via the remodeling of unbalanced gut microbiota and metabolism in vivo, providing an antitumor therapy strategy.     

二维材料MXene的储能性能与应用

能量存储和转化器件是现代社会的重要基础。随着清洁能源、便携式电子设备及电动汽车的快速发展,人们对储能器件性能的要求越来越高。储能材料是决定储能器件性能的重要因素。通常,储能材料需满足具有可逆的氧化还原反应、易于电解液离子脱嵌、尽可能多地提供氧化还原位点、良好的导电能力等要求。近年来,二维材料因比表面积大、离子传输路径短等特点而得到广泛关注,在储能领域也具有巨大的发展潜力。只有原子量级厚度的二维材料,表面活性位点多,力学性能优良,正契合储能器件对电极材料的要求。MXene是一类新型二维材料,通式为Mn+1XnTx,其中M代表过渡族金属元素,X为碳和/或氮,T代表MXene在制备过程中产生的官能团(-F、-OH、-O等),n一般为1～4。自2011年首次报道以来,MXene在储能领域就被寄予厚望。MXene含有碳原子层,所以具有类似石墨烯的良好导电性;而过渡金属层使其表现出类似过渡金属氧化物的性能;同时,表面多样的官能团赋予MXene良好的亲水性。这种独特的性能组合,使得MXene电荷响应速度快,具有赝电容特征且循环性能稳定,成为储能领域的研究焦点。另外,便携式储能器件要求更高的体积容量与体积能量密度,而MXene与碳基电极材料相比堆积密度高,可有效降低器件体积,拓展应用范围。目前,MXene及其复合材料已经在超级电容器、锂/钠/镁离子二次电池、锂硫电池、锌-空气电池、储氢等诸多储能领域展现出实用价值。但是,MXene容易发生塌陷和堆垛,影响其作为电极材料的性能。因此,需将MXene进行插层、改性、掺杂或与其他材料复合,以阻止MXene堆叠,减小离子扩散阻力,并增加离子吸附位点,从而提高其电化学性能。而且,不同的能量存储和转化装置对MXene的合成方法和结构特征有不同的要求,鉴于MXene能源应用相关研究的大量呈现,有必要对其进行全面总结与分析,以期推动MXene在该领域的发展。本文旨在综述MXene在制备、结构、性能及其在储能方面的最新研究动态与发展方向,并讨论面临的挑战。     

2D Transition Metal Carbides (MXenes) for Carbon Capture

Global warming caused by burning of fossil fuels is indisputably one of mankind's greatest challenges in the 21st century. To reduce the ever‐increasing CO₂ emissions released into the atmosphere, dry solid adsorbents with large surface‐to‐volume ratio such as carbonaceous materials, zeolites, and metal–organic frameworks have emerged as promising material candidates for capturing CO₂. However, challenges remain because of limited CO₂/N₂ selectivity and long‐term stability. The effective adsorption of CO₂ gas (≈12 mol kg^?1) on individual sheets of 2D transition metal carbides (referred to as MXenes) is reported here. It is shown that exposure to N₂ gas results in no adsorption, consistent with first‐principles calculations. The adsorption efficiency combined with the CO₂/N₂ selectivity, together with a chemical and thermal stability, identifies the archetype Ti₃C₂ MXene as a new material for carbon capture (CC) applications.     

Mesoporous Silica Supported Silver–Bismuth Nanoparticles as Photothermal Agents for Skin Infection Synergistic Antibacterial Therapy

The emergence of multidrug resistant bacteria has resulted in plenty of stubborn nosocomial infections and severely threatens human health. Developing novel bactericide and therapeutic strategy is urgently needed. Herein, mesoporous silica supported silver–bismuth nanoparticles (Ag‐Bi@SiO₂ NPs) are constructed for synergistic antibacterial therapy. In vitro experiments indicate that the hyperthermia originating from Bi NPs can disrupt cell integrity and accelerate the Ag ions release, further exhibiting an excellent antibacterial performance toward methicillin‐resistant Staphylococcus aureus (MRSA). Besides, under laser irradiation, Ag‐Bi@SiO₂ NPs at 100 µg mL^?1 can effectively obliterate mature MRSA biofilm and cause a 69.5% decrease in the biomass, showing a better therapeutic effect than Bi@SiO₂ NPs with laser (26.8%) or Ag‐Bi@SiO₂ NPs without laser treatment (30.8%) groups. More importantly, in vivo results confirm that ≈95.4% of bacteria in abscess are killed and the abscess ablation is accelerated using the Ag‐Bi@SiO₂ NPs antibacterial platform. Therefore, Ag‐Bi@SiO₂ NPs with photothermal‐enhanced antibacterial activity are a potential nano‐antibacterial agent for the treatment of skin infections.     

In Vivo Bio‐Safety Evaluations and Diagnostic/Therapeutic Applications of Chemically Designed Mesoporous Silica Nanoparticles

The remarkable progress of nanotechnology and its application in biomedicine have greatly expanded the ranges and types of biomaterials from traditional organic material‐based nanoparticles (NPs) to inorganic biomaterials or organic/inorganic hybrid nanocomposites due to the unprecedented advantages of the engineered inorganic material‐based NPs. Colloidal mesoporous silica NPs (MSNs), one of the most representative and well‐established inorganic materials, have been promoted into biology and medicine, and shifted from extensive in vitro research towards preliminary in vivo assays in small‐animal disease models. In this comprehensive review, the recent progresses in chemical design and engineering of MSNs‐based biomaterials for in vivo biomedical applications has been detailed and overviewed. Due to the intrinsic structural characteristics of elaborately designed MSNs such as large surface area, high pore volume and easy chemical functionalization, they have been extensively investigated for therapeutic, diagnostic and theranostic (concurrent diagnosis and therapy) purposes, especially in oncology. Systematic in vivo bio‐safety evaluations of MSNs have revealed the evidences that the in vivo bio‐behaviors of MSNs are strongly related to their preparation prodecures, particle sizes, geometries, surface chemistries, dosing parameters and even administration routes. In vivo pharmacokinetics and pharmacodynamics further demonstrated the effectiveness of MSNs as the passively and/or actively targeted drug delivery systems (DDSs) for cancer chemotherapy. Especially, the advance of nano‐synthetic chemistry enables the production of composite MSNs for advanced in vivo therapeutic purposes such as gene delivery, stimuli‐responsive drug release, photothermal therapy, photodynamic therapy, ultrasound therapy, or anti‐bacteria in tissue engineering, or as the contrast agents for biological and diagnostic imaging. Additionally, the critical issues and potential challenges related to the chemical design/synthesis of MSNs‐based “magic bullet” by advanced nano‐synthetic chemistry and in vivo evaluation have been discussed to highlight the issues scientists face in promoting the translation of MSNs‐based DDSs into clinical trials.     

Iron‐Oxide‐Based Nanovector for Tumor Targeted siRNA Delivery in an Orthotopic Hepatocellular Carcinoma Xenograft Mouse Model

Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Small interfering RNA (siRNA) holds promise as a new class of therapeutics for HCC, as it can achieve sequence‐specific gene knockdown with low cytotoxicity. However, the main challenge in the clinical application of siRNA lies in the lack of effective delivery approaches that need to be highly specific and thus incur low or no systemic toxicity. Here, a nonviral nanoparticle‐based gene carrier is presented that can specifically deliver siRNA to HCC. The nanovector (NP‐siRNA‐GPC3 Ab) is made of an iron oxide core coated with chitosan‐polyethylene glycol (PEG) grafted polyethyleneimine copolymer, which is further functionalized with siRNA and conjugated with a monoclonal antibody (Ab) against human glypican‐3 (GPC3) receptor highly expressed in HCC. A rat RH7777 HCC cell line that coexpresses human GPC3 and firefly luciferase (Luc) is established to evaluate the nanovector. The nanoparticle‐mediated delivery of siRNA against Luc effectively suppresses Luc expression in vitro without notable cytotoxicity. Significantly, NP‐siLuc‐GPC3 Ab administered intravenously in an orthotopic model of HCC is able to specifically bound to tumor and induce remarkable inhibition of Luc expression. The findings demonstrate the potential of using this nanovector for targeted delivery of therapeutic siRNA to HCC.     

Renal Clearable Catalytic 2D Au–Porphyrin Coordination Polymer Augmented Photothermal-Gas Synergistic Cancer Therapy

As a gasotransmitter, carbon monoxide (CO) possesses antitumor activity by reversing the Warburg effect at higher concentrations. The targeted delivery of carbon monoxide-releasing molecules (CORMs) using nanomaterials is an appealing option for CO administration, but how to maintain CO above the threshold concentration in tumor tissue remains a challenge. Herein, a nanozyme-catalyzed cascade reaction is proposed to promote CO release for high-efficacy photothermal therapy (PTT)-combined CO therapy of cancer. A gold-based porphyrinic coordination polymer nanosheet (Au⁰–Por) is synthesized to serve as a carrier for CORM. It also possesses excellent glucose oxygenase-like activity owing to ultrasmall zero-valent gold atoms on the nanosheet. The catalytically generated H₂O₂ can efficiently catalyze CORM decomposition, which enables in situ generation of sufficient CO for gas therapy. In vivo, the Au⁰–Por nanosheets-enhanced photoacoustic imaging (PAI) and fluorescence imaging collectively demonstrate high tumor-targeting efficiency and nanomaterial retention. Proven to have augmented therapeutic efficacy, the nanoplatform can also be easily degraded and excreted through the kidney, indicating good biocompatibility. Thus, the application of rational designed Au⁰–Por nanosheet with facile approach and biodegradable property to PAI-guided synergistic gas therapy can provide a strategy for the development of biocompatible and highly effective gaseous nanomedicine.     

Systematic Engineering of Uniform,Highly Efficient,Targeted and Shielded Viral‐Mimetic Nanoparticles

In the past decades, numerous types of nanomedicines have been developed for the efficient and safe delivery of nucleic acid‐based drugs for cancer therapy. Given that the destination sites for nucleic acid‐based drugs are inside cancer cells, delivery systems need to be both targeted and shielded in order to overcome the extracellular and intracellular barriers. One of the major obstacles that has hindered the translation of nanotechnology‐based gene‐delivery systems into the clinic has been the complexity of the design and assembly processes, resulting in non‐uniform nanocarriers with unpredictable surface properties and efficiencies. Consequently, no product has reached the clinic yet. In order to address this shortcoming, a multifunctional targeted biopolymer is genetically engineered in one step, eliminating the need for multiple chemical conjugations. Then, by systematic modulation of the ratios of the targeted recombinant vector to PEGylated peptides of different sizes, a library of targeted–shielded viral‐mimetic nanoparticles (VMNs) with diverse surface properties are assembled. Through the use of physicochemical and biological assays, targeted–shielded VMNs with remarkably high transfection efficiencies (>95%) are screened. In addition, the batch‐to‐batch variability of the assembled targeted–shielded VMNs in terms of uniformity and efficiency is examined and, in both cases, the coefficient of variation is calculated to be below 20%, indicating a highly reproducible and uniform system. These results provide design parameters for engineering uniform, targeted–shielded VMNs with very high cell transfection rates that exhibit the important characteristics for in vivo translation. These design parameters and principles could be used to tailor‐make and assemble targeted–shielded VMNs that could deliver any nucleic acid payload to any mammalian cell type.     

Enhanced Photothermal Therapy through the In Situ Activation of a Temperature and Redox Dual‐Sensitive Nanoreservoir of Triptolide

Photothermal therapy (PTT) has attracted tremendous attention due to its noninvasiveness and localized treatment advantages. However, heat shock proteins (HSPs) associated self‐preservation mechanisms bestow cancer cells thermoresistance to protect them from the damage of PTT. To minimize the thermoresistance of cancer cells and improve the efficacy of PTT, an integrated on‐demand nanoplatform composed of a photothermal conversion core (gold nanorod, GNR), a cargo of a HSPs inhibitor (triptolide, TPL), a mesoporous silica based nanoreservoir, and a photothermal and redox di‐responsive polymer shell is developed. The nanoplatform can be enriched in the tumor site, and internalized into cancer cells, releasing the encapsulated TPL under the trigger of intracellular elevated glutathione and near‐infrared laser irradiation. Ultimately, the liberated TPL could diminish thermoresistance of cancer cells by antagonizing the PTT induced heat shock response via multiple mechanisms to maximize the PTT effect for cancer treatment.     

Synergistic Targeting of Cancer and Associated Angiogenesis Using Triple‐Targeted Dual‐Drug Silica Nanoformulations for Theragnostics

The targeting and therapeutic efficacy of dye‐ and dual‐drug‐loaded silica nanoparticles, functionalized with triple targeting ligands specific towards cancer and neoangiogenesis simultaneously, are discussed. This synergized, high‐precision, multitarget concept culminates in an elevated uptake of nanoparticles by cancer and angiogenic cells with amplified proficiency, thereby imparting superior therapeutic efficacy against breast cancer cells and completely disabling the migration and angiogenic sprouting ability of activated endothelial cells. The exceptional multimodal efficiency achieved by this single therapeutic nanoformulation holds promise for the synergistic targeting and treatment of the yet elusive cancer and its related angiogenesis in a single, lethal shot.     

Targeted hepatocellular carcinoma therapy: transferrin modified,self-assembled polymeric nanomedicine for co-delivery of cisplatin and doxorubicin

Background: Targeted hepatocellular carcinoma (HCC) therapy was carried out to improve the efficacy of liver cancers. The aim of this study was to develop transferrin (Tf) modified, self-assembled polymeric nanoparticles for co-delivery doxorubicin (DOX) and cisplatin (DDP), to achieve combination tumor therapy.

Methods: Tf modified polyethylene glycol (PEG) containing DOX prodrug (Tf-PEG-DOX) was synthesized. DDP containing poly(lactic-co-glycolic) acid (PLGA) materials (PLGA-DDP) were prepared. Tf modified DOX and DDP loaded PLGA nanoparticles (Tf-DOX/DDP NPs) were prepared by using nanoprecipitation method. The particles sizes, zeta potentials, drug loading effects were characterized. The cytotoxicity of the NPs was evaluated in human hepatoma carcinoma cell lines (HepG2 cells), and in vivo anti-tumor was observed in mice bearing human HepG2 cells model.

Results: Tf-DOX/DDP NPs displayed higher cytotoxicity and enhanced antitumor activity both in vitro and in vivo over their non-modified and single drug loaded counterparts.

Conclusion: Tf-DOX/DDP NPs can achieve outstanding anti-tumor activity due to the combination effect of two drugs and the active targeting ability of Tf ligands. The self-assembled polymeric nanomedicine could act as an efficient therapy method for HCC treatment.