Paraptosis‐Inducing Nanomedicine Overcomes Cancer Drug Resistance for a Potent Cancer Therapy

Most chemotherapeutic drugs and their nanomedicine formulations exert anticancer activity by inducing cancer cell apoptosis. However, cancer cells inherently have and acquire many antiapoptosis mechanisms, causing cancer drug resistance and poor prognoses in patients. Herein, a potent paraptosis‐inducing nanomedicine is reported that causes quick nonapoptotic death of cancer cells, overcoming apoptosis‐based resistance and effectively inhibiting drug‐resistant tumor growth. The nanomedicine is composed of micelles made from an amphiphilic 8‐hydroxyquinoline (HQ)‐conjugate block copolymer with polyethylene glycol. Cu²⁺ can catalyze the hydrolysis of the HQ conjugation linker and liberate HQ, and these molecules can form the complex Cu(HQ)₂, a strong proteasome inhibitor effective at inducing cell paraptosis. In vivo, the Cu²⁺‐responsive HQ‐releasing micelles respond to elevated tumor Cu²⁺ levels or externally administered Cu²⁺ and effectively inhibit the growth of human breast adenocarcinoma doxorubicin‐resistant (MCF‐7/ADR) tumors. Compared with other nanomedicines that overcome drug resistance via delivering several agents or even siRNA, this paraptosis‐inducing nanomedicine provides a simple but potent approach to overcoming cancer drug resistance.     

T-Cell-Mimicking Nanoparticles for Cancer Immunotherapy

Cancer immunotherapies, including adoptive T cell transfer and immune checkpoint blockades, have recently shown considerable success in cancer treatment. Nevertheless, transferred T cells often become exhausted because of the immunosuppressive tumor microenvironment. Immune checkpoint blockades, in contrast, can reinvigorate the exhausted T cells; however, the therapeutic efficacy is modest in 70–80% of patients. To address some of the challenges faced by the current cancer treatments, here T-cell-membrane-coated nanoparticles (TCMNPs) are developed for cancer immunotherapy. Similar to cytotoxic T cells, TCMNPs can be targeted at tumors via T-cell-membrane-originated proteins and kill cancer cells by releasing anticancer molecules and inducing Fas-ligand-mediated apoptosis. Unlike cytotoxic T cells, TCMNPs are resistant to immunosuppressive molecules (e.g., transforming growth factor-β1 (TGF-β1)) and programmed death-ligand 1 (PD-L1) of cancer cells by scavenging TGF-β1 and PD-L1. Indeed, TCMNPs exhibit higher therapeutic efficacy than an immune checkpoint blockade in melanoma treatment. Furthermore, the anti-tumoral actions of TCMNPs are also demonstrated in the treatment of lung cancer in an antigen-nonspecific manner. Taken together, TCMNPs have a potential to improve the current cancer immunotherapy.     

Adjuvant‐Loaded Subcellular Vesicles Derived From Disrupted Cancer Cells for Cancer Vaccination

Targeted subunit vaccines for cancer immunotherapy do not capture tumor antigenic complexity, and approaches employing tumor lysate are often limited by inefficient antigen uptake and presentation, and low immunogenicity. Here, whole cancer cells are processed to generate antigen‐rich, membrane‐enclosed subcellular particles, termed “reduced cancer cells”, that reflect the diversity and breadth of the parent cancer cell antigen repertoire, and can be loaded with disparate adjuvant payloads. These vesicular particles enhance the uptake of the adjuvant payload, and potentiate the activation of primary dendritic cells in vitro. Similarly, reduced cancer cell‐associated antigens are more efficiently presented by primary dendritic cells in vitro than their soluble counterparts or lysate control. In mice, vaccination using adjuvant‐loaded reduced cancer cells facilitates the induction of antigen‐specific cellular and humoral immune responses. Taken together, these observations demonstrate that adjuvant‐loaded reduced cancer cells could be utilized in cancer vaccines as an alternative to lysate.     

Cell-Based Drug Delivery Systems Participate in the Cancer Immunity Cycle for Improved Cancer Immunotherapy

Immunotherapy aims to activate the cancer patient's immune system for cancer therapy. The whole process of the immune system against cancer referred to as the “cancer immunity cycle”, gives insight into how drugs can be designed to affect every step of the anticancer immune response. Cancer immunotherapy such as immune checkpoint inhibitor (ICI) therapy, cancer vaccines, as well as small molecule modulators has been applied to fight various cancers. However, the effect of immunotherapy in clinical applications is still unsatisfactory due to the limited response rate and immune-related adverse events. Mounting evidence suggests that cell-based drug delivery systems (DDSs) with low immunogenicity, superior targeting, and prolonged circulation have great potential to improve the efficacy of cancer immunotherapy. Therefore, with the rapid development of cell-based DDSs, understanding their important roles in various stages of the cancer immunity cycle guides the better design of cell-based cancer immunotherapy. Herein, an overview of how cell-based DDSs participate in cancer immunotherapy at various stages is presented and an outlook on possible challenges of clinical translation and application in future development.     

Photoactivatable Protherapeutic Nanomedicine for Cancer

Therapeutic systems with site-specific pharmaceutical activation hold great promise to enhance therapeutic efficacy while reducing systemic toxicity in cancer therapy. With operational flexibility, noninvasiveness, and high spatiotemporal resolution, photoactivatable nanomedicines have drawn growing attention. Distinct from traditional controlled release systems relying on the difference of biomarker concentrations between disease and healthy tissues, photoactivatable nanomedicines capitalize on the interaction between nanotransducers and light to either trigger photochemical reactions or generate reactive oxygen species (ROS) or heat effect to remotely induce pharmaceutical actions in living subjects. Herein, the recent advances in the development of photoactivatable protherapeutic nanoagents for oncology are summarized. The design strategies and therapeutic applications of these nanoagents are described. Representative examples of each type are discussed in terms of structure, photoactivation mechanism, and preclinical models. Last, potential challenges and perspectives to further develop photoactivatable protherapeutic nanoagents in cancer nanomedicine are discussed.     

Carbon Dots Seek out Cancer

<正>In recent years,carbon nanoparticles called carbon dots(CD),have displayed the ability to photoluminescence when surface functionalized with polymer chains.This phenomenon is similar to the photoluminescence observed in carbon nanotubes and carbon nanodiamonds.While the mechanism of this phenomenon has only been theorized.Researchers have demonstrated the capacity to tailor the optical properties of the carbon dot by     

Targeting Neutrophils for Enhanced Cancer Theranostics

Improving tumor accumulation and delivery efficiency is an important goal of nanomedicine. Neutrophils play a vital role in both chemically mediating inflammatory response through myeloperoxidase (MPO) and biologically promoting metastasis during inflammation triggered by the primary tumor or environmental stimuli. Herein, a novel theranostic nanomedicine that targets both the chemical and biological functions of neutrophils in tumor is designed, facilitating the enhanced retention and sustained release of drug cargos for improved cancer theranostics. 5-hydroxytryptamine (5-HT) is equipped onto nanoparticles (NPs) loaded with photosensitizers and Zileuton (a leukotriene inhibitor) to obtain MPO and neutrophil targeting NPs, denoted as HZ-5 NPs. The MPO targeting property of 5-HT modified NPs is confirmed by noninvasive positron emission tomography imaging studies. Furthermore, photodynamic therapy is used to initiate the inflammatory response which further mediated the accumulation and retention of neutrophil targeting NPs in a breast cancer model. This design renders a greatly improved theranostic nanomedicine for efficient tumor suppression, and more importantly, inhibition of neutrophil-mediated lung metastasis via the sustained release of Zileuton. This work presents a novel strategy of targeting neutrophils for improved tumor theranostics, which may open up new avenues in designing nanomedicine through exploiting the tumor microenvironment.     

NaCl Nanoparticles as a Cancer Therapeutic

Many inorganic nanoparticles are prepared and their behaviors in living systems are investigated. Yet, common electrolytes such as NaCl are left out of this campaign. The underlying assumption is that electrolyte nanoparticles will quickly dissolve in water and behave similarly as their constituent salts. Herein, this preconception is challenged. The study shows that NaCl nanoparticles (SCNPs) but not salts are highly toxic to cancer cells. This is because SCNPs enter cells through endocytosis, bypassing cell regulations on ion transport. When dissolved inside cancer cells, SCNPs cause a surge of osmolarity and rapid cell lysis. Interestingly, normal cells are much more resistant to the treatment due to their relatively low sodium levels. Unlike conventional chemotherapeutics, SCNPs cause immunogenic cell death or ICD. In vivo studies show that SCNPs not only kill cancer cells, but also boost an anticancer immunity. The discovery opens up a new perspective on nanoparticle‐based therapeutics.     

肺癌细胞微团的低温保存实验

细胞微团、细胞聚集体所构建的三维细胞模型在肿瘤研究领域中逐渐成为更合适的体外研究模型,但目前对于细胞微团的低温保存方法尚不完善.本文研究了A549肺癌细胞的接种密度以及培养天数对肺癌细胞微团尺寸及生长状态的影响,结果表明:接种密度为2×104个/mL,培养三天的肺癌细胞微团状态良好,可形成致密的结构,微团直径为344....     

SPION@APTES@FA-PEG@Usnic Acid Bionanodrug for Cancer Therapy

In this work, we aimed to develop stable usnic acid (UA)-conjugated superparamagnetic iron oxide nanoparticles (SPIONs) as a potential drug carrier for in vitro analysis of MCF-7 (breast cancer cell line), HeLa (cervix cancer cell line), L929 (mouse fibroblast cell line), U87 (glioblastoma cell line, brain cancer), and A549 (human lung cancer cell line) cell lines. SPIONs were synthesized via the polyol method and functionalized with APTES using the Stöber method. Carboxylated polyethylene glycol (PEG-COOH), folic acid (FA), and carboxylated luteolin (CL) were conjugated on the surface via a carboxylic/amine group using the nanoprecipitation method, respectively. X-ray powder diffraction analysis confirmed the purity of the product with crystallite size of around 11 nm. Fourier-transformed infrared spectrophotometer (FT-IR) analyses explained the conjugation of all functional groups to the surface of SPIONs. The percentages of inorganic and organic content in the products were investigated via thermal gravimetric analyzer (TGA). For morphological analysis, a transmission electron microscope (TEM) was used. The superparamagnetic property of the product was also confirmed by vibrating sample magnetometer (VSM).     

Attacking Cancer Tumors with Tiny Discs

<正>The idea that magnetic particles could be used to target cancer tumors has been in the research community for several decades.The general principle is that drugs intended to destroy targeted cells could be attached to magnetic particles and guided to the appropriate places in the human body using external magnetic fields.     

Organic Dye Based Nanoparticles for Cancer Phototheranostics

Phototheranostics, which simultaneously combines photodynamic and/or photothermal therapy with deep‐tissue diagnostic imaging, is a promising strategy for the diagnosis and treatment of cancers. Organic dyes with the merits of strong near‐infrared absorbance, high photo‐to‐radical and/or photothermal conversion efficiency, great biocompatibility, ready chemical structure fine‐tuning capability, and easy metabolism, have been demonstrated as attractive candidates for clinical phototheranostics. These organic dyes can be further designed and fabricated into nanoparticles (NPs) using various strategies. Compared to free molecules, these NPs can be equipped with multiple synergistic functions and show longer lifetime in blood circulation and passive tumor‐targeting property via the enhanced permeability and retention effect. In this article, the recent progress of organic dye‐based NPs for cancer phototheranostic applications is summarized, which extends the anticancer arsenal and holds promise for clinical uses in the near future.     

Immunology-Guided Biomaterial Design for Mucosal Cancer Vaccines

Cancer of mucosal tissues is a major cause of worldwide mortality for which only palliative treatments are available for patients with late-stage disease. Engineered cancer vaccines offer a promising approach for inducing antitumor immunity. The route of vaccination plays a major role in dictating the migratory pattern of lymphocytes, and thus vaccine efficacy in mucosal tissues. Parenteral immunization, specifically subcutaneous and intramuscular, is the most common vaccination route. However, this induces marginal mucosal protection in the absence of tissue-specific imprinting signals. To circumvent this, the mucosal route can be utilized, however degradative mucosal barriers must be overcome. Hence, vaccine administration route and selection of materials able to surmount transport barriers are important considerations in mucosal cancer vaccine design. Here, an overview of mucosal immunity in the context of cancer and mucosal cancer clinical trials is provided. Key considerations are described regarding the design of biomaterial-based vaccines that will afford antitumor immune protection at mucosal surfaces, despite limited knowledge surrounding mucosal vaccination, particularly aided by biomaterials and mechanistic immune–material interactions. Finally, an outlook is given of how future biomaterial-based mucosal cancer vaccines will be shaped by new discoveries in mucosal vaccinology, tumor immunology, immuno-therapeutic screens, and material–immune system interplay.     

影像组学在肺癌中的应用研究进展

影像组学是从医学图像中提取大量的定量影像学特征,通过捕获整个肿瘤位置、范围、形态等和从3D图像中提取影像信息,旨在从临床影像学数据中提取肿瘤表型信息.已有大量研究表明,影像组学在肺癌的诊断和治疗中具有较大优势,影像组学已经发展成为辅助诊断、分析和预测肺癌转移的工具,现就影像组学在肺癌中的应用研究进展进行综述.     

2D Nanomaterials for Cancer Theranostic Applications

2D nanomaterials with unique nanosheet structures, large surface areas, and extraordinary physicochemical properties have attracted tremendous interest. In the area of nanomedicine, research on graphene and its derivatives for diverse biomedical applications began as early as 2008. Since then, many other types of 2D nanomaterials, including transition metal dichalcogenides, transition metal carbides, nitrides and carbonitrides, black phosphorus nanosheets, layered double hydroxides, and metal–organic framework nanosheets, have been explored in the area of nanomedicine over the past decade. In particular, a large surface area makes 2D nanomaterials highly efficient drug delivery nanoplatforms. The unique optical and/or X-ray attenuation properties of 2D nanomaterials can be harnessed for phototherapy or radiotherapy of cancer. Furthermore, by integrating 2D nanomaterials with other functional nanoparticles or utilizing their inherent physical properties, 2D nanomaterials may also be engineered as nanoprobes for multimodal imaging of tumors. 2D nanomaterials have shown substantial potential for cancer theranostics. Herein, the latest progress in the development of 2D nanomaterials for cancer theranostic applications is summarized. Current challenges and future perspectives of 2D nanomaterials applied in nanomedicine are also discussed.     

Tumor-Targeting Glycol Chitosan Nanoparticles for Cancer Heterogeneity

Nanomedicine is extensively employed for cancer treatment owing to its unique advantages over conventional drugs and imaging agents. This increased attention to nanomedicine, however, has not fully translated into clinical utilization and patient benefits due to issues associated with reticuloendothelial system clearance, tumor heterogeneity, and complexity of the tumor microenvironment. To address these challenges, efforts are being made to modify the design of nanomedicines, including optimization of their physiochemical properties, active targeting, and response to stimuli, but these studies are often performed independently. Combining favorable nanomedicine designs from individual studies may improve therapeutic outcomes, but, this is difficult to achieve as the effects of different designs are interconnected and often conflicting. Glycol chitosan nanoparticles (CNPs) are shown to accumulate in tumors, suggesting that this type of nanoparticle may constitute a good basis for the additional modification of nanoparticles. Here, multifunctional glycol CNPs designed to overcome multiple obstacles to their use are described and key factors influencing in vivo targeted delivery, targeting strategies, and interesting stimulus-responsive designs for improving cancer nanomedicine are discussed.