Achieving the activation of drugs within cellular systems may provide targeted therapies. Here we construct a tumour-selective cascade activatable self-detained system (TCASS) and incorporate imaging ...probes and therapeutics. We show in different mouse models that the TCASS system accumulates in solid tumours. The molecules show enhanced accumulation in tumour regions via the effect of recognition induced self-assembly. Analysis of the molecular penetration in tumour tissue shows that in vivo self-assembly increases the penetration capability compared to typical soft or hard nanomaterials. Importantly, the in vivo self-assembled molecules exhibit a comparable clearance pathway to that of small molecules, which are excreted from organs of the reticuloendothelial system (liver and kidney), while are relatively slowly eliminated from tumour tissues. Finally, this system, combined with the NIR probe, shows high specificity and sensitivity for detecting bladder cancer in isolated intact patient bladders.
Topological structures of bio-architectonics and bio-interfaces play major roles in maintaining the normal functions of organs, tissues, extracellular matrix, and cells. In-depth understanding of ...natural self-assembly mechanisms and mimicking functional structures provide us opportunities to artificially control the natural assemblies and their biofunctions. Here, we report an intracellular enzyme-catalyzed polymerization approach for efficient synthesis of polypeptides and in situ construction of topology-controlled nanostructures. We reveal that the phase behavior and topological structure of polypeptides are encoded in monomeric peptide sequences. Next, we elucidate the relationship between polymerization dynamics and their temperature-dependent topological transition in biological conditions. Importantly, the linearly grown elastin-like polypeptides are biocompatible and aggregate into nanoparticles that exhibit significant molecular accumulation and retention effects. However, 3D gel-like structures with thermo-induced multi-directional traction interfere with cellular fates. These findings allow us to exploit new nanomaterials in living subjects for biomedical applications.
A peptide‐conjugated poly(β‐amino ester) that self‐assembles into micelle‐like nanoparticles is prepared by a convenient and modular supramolecular approach. The polymer–beclin‐1 (P‐Bec1) ...nanoparticles display enhanced cytotoxicity to breast cancer cells through induction of autophagy. This approach overcomes two major limitations of the haploinsufficient tumor suppressor Bec1 compared to small‐molecule drugs: poor delivery to tumors owing to enzymatic degradation, and unstable, non‐specific bio‐distribution and targeting in the tumor tissues.
Posterior capsule opacification (PCO) is the most common complication after cataract surgery. So far, the only method for PCO treatment is the precisely focused laser surgery. However, it causes ...severe complications such as physical damages and neuron impairments. Here, a nanostructured photothermal ring integrated intraocular lens (Nano‐IOLs) is reported, in which the rim of commercially available IOLs (C‐IOLs) is decorated with silica coated Au nanorods (Au@SiO2), for high‐efficient prevention of PCO after cataract surgery. The Nano‐IOLs is capable of eliminating the residual lens epithelial cells (LECs) around Nano‐IOLs under mild laser treatment and block the formation of disordered LECs fibrosis, which eventually leads to the loss of vision. The Nano‐IOLs shows good biocompatibility as well as extraordinary region‐confined photothermal effect. In vivo studies reveal that PCO occurrence in rabbit models is about 30%–40% by using Nano‐IOLs, which is significantly lower than the control group that treated with C‐IOLs (100% PCO occurrence) 30 d postsurgery. To the best of our knowledge, it is the first example to integrate nanotechnology with intraocular implants aiming to clinically relevant PCO. Our findings indicate that spatial controllability of photothermal effect from nanomaterials may provide a unique way to intervene the PCO‐induced loss of vision.
An intraocular lens with a Au@SiO2 nanorod‐modified rim (Nano‐IOLs) is reported. Compared to the commercially available IOLs, these Nano‐IOLs retain the intrinsic biocompatibility and optical properties and meanwhile exhibit extraordinary region‐confined photothermal effect. In vitro and rabbit experimental results confirm that the Nano‐IOLs can effectively kill LECs near to the rim and effectively prevent the occurrence of posterior capsule opacification.
Abstract Immunotherapy has shown a promising effect for a variety of cancers. However, the immune treatment efficiency of solid tumor is limited due to barely infiltration of immune cells in solid ...tumor. Researchers realized conversion of tumor supportive macrophages to tumor against ones was an effective method to induce the functional reverse of macrophage and contributed to the subsequent antitumor response. The current challenge in the field is that while making use of cytokines usually coupled with poor-distribution and systemic side effects. As a solution to this issue, we designed and synthesized microenvironment-responsive nanoparticles (P) with IL-12 payload (IL-12⊂P1), the IL-12⊂P1 which could adopt by systemic administration and release IL-12 in the tumor microenvironment, the local-responsive property of IL-12⊂P1 re-educate tumor-associated macrophages (TAMs) subsequently. Particularly, it illustrated great therapeutic effects which derived from functional conversion of macrophages. Our strategy was to design a microenvironment-responsive material for local macrophage reverse modification which could overcome the physiological barrier of solid tumor. The shifting of macrophages by IL-12⊂P1 realized immunomodulation in microenvironment for cancer therapy with negligible cytotoxicity. We expected that regulating the function of TAMs by pH-responsive nanomaterials would be a promising therapeutic approach for cancer immunotherapy.
Smart nanorobots have emerged as novel drug delivery platforms in nanomedicine, potentially improving anti‐cancer efficacy and reducing side effects. In this study, an intelligent tumor ...microenvironment‐responsive nanorobot is developed that effectively delivers CpG payloads to Toll‐like receptor 9 (TLR9)‐positive tumors to induce autophagy‐mediated cell death for immunotherapy. The nanorobots are fabricated by co‐self‐assembly of two amphiphilic triblock polymer peptides: one containing the matrix metallopeptidase 2 (MMP2)‐cleaved GPLGVRGS motif to control the mechanical opening of the nanorobots and provide targeting capability for TLR‐9‐positive tumors and the other consisting of an arginine‐rich GRRRDRGRS sequence that can condense nuclear acid payloads through electrostatic interactions. Using multiple tumor‐bearing mouse models, it is investigated whether the intravenous injection of CpG‐loaded nanorobots could effectively deliver CpG payloads to TLR‐9‐positive tumors and elicit anti‐tumor immunity through TLR9 signaling and autophagy. Therefore, besides being a commonly used adjuvant for tumor vaccination, CpG‐loaded nanorobots can effectively reprogram the tumor immunosuppressive microenvironment and suppress tumor growth and recurrence. This nanorobot‐based CpG immunotherapy can be considered a feasible approach to induce anti‐tumor immunity, showing great therapeutic potential for the future treatment of TLR9‐positive cancers.
In this study, an intelligent tumor microenvironment‐responsive nanorobot is developed that effectively delivers CpG payloads to Toll‐like receptor 9 (TLR9)‐positive tumors to induce autophagy‐mediated cell death for immunotherapy.
Layered double hydroxides (LDH) are a class of functional anionic clays that typically consist of orthorhombic arrays of metal hydroxides with anions sandwiched between the layers. Due to their ...unique properties, including high chemical stability, good biocompatibility, controlled drug loading, and enhanced drug bioavailability, LDHs have many potential applications in the medical field. Especially in the fields of bioimaging and tumor therapy. This paper reviews the research progress of LDHs and their nanocomposites in the field of tumor imaging and therapy. First, the structure and advantages of LDH are discussed. Then, several commonly used methods for the preparation of LDH are presented, including co‐precipitation, hydrothermal and ion exchange methods. Subsequently, recent advances in layered hydroxides and their nanocomposites for cancer imaging and therapy are highlighted. Finally, based on current research, we summaries the prospects and challenges of layered hydroxides and nanocomposites for cancer diagnosis and therapy.
This paper reviews scientific and technological advances in LDH‐based nanomaterials for tumour imaging and therapy, including an analysis of their structures and advantages, a detailed description of their synthesis methods, and a discussion of their cutting‐edge potential and future directions in tumour diagnosis and therapy.
Immunotherapy has shown promising treatment effects for a variety of cancers. However, the immune treatment efficiency for solid tumors is limited owing to insufficient infiltration of immune cells ...into solid tumors. The conversion of tumor-supportive macrophages to tumor-suppressive macrophages, inducing the functional reversal of macrophages, is an effective method and contributes to a subsequent antitumor response. The current challenge in the field is the poor distribution and systemic side effects associated with the use of cytokines. As a solution to this issue, we designed and synthesized microenvironment-responsive nanoparticles (P) with IL-12 payload (IL-12⊂P1). These nanoparticles could promote the systemic administration and release of IL-12 in the tumor microenvironment, and the locally responsive property of IL-12⊂P1 could subsequently re-educate tumor-associated macrophages (TAMs). In particular, our results illustrated the great therapeutic effects derived from the functional conversion of macrophages. Our strategy was to design a microenvironment-responsive material for local macrophage modification to overcome the physiological barrier of solid tumors. The shifting of macrophage phenotypes via IL-12⊂P1 achieved immunomodulation in the microenvironment for cancer therapy, with negligible cytotoxicity. We expect that the functional regulation of TAMs by pH-responsive nanomaterials is a promising therapeutic approach for cancer immunotherapy.
A universal strategy for efficient, mild, and purification‐free synthesis and in situ screening of functional polymer‐peptide nanomaterials is described. More than 1000 polymer–peptide conjugates ...(PPCs) with various chemical structures, compositions, and therapeutic efficacy are created. According to this strategy, the structure–function relationship of the PPCs is revealed, and the antitumor efficacies of the top performing PPCs are evaluated in vivo.
Autophagy plays a crucial role in the metabolic process. So far, conventional methods are incapable of rapid, precise, and real-time monitoring of autophagy in living objects. Herein, we describe an ...in situ intracellular self-assembly strategy for quantitative and temporal determination of autophagy in living objectives. The intelligent building blocks (DPBP) are composed by a bulky dendrimer as a carrier, a bis(pyrene) derivative (BP) as a signal molecule, and a peptide linker as a responsive unit that can be cleaved by an autophagy-specific enzyme, i.e., ATG4B. DPBP maintains the quenched fluorescence with monomeric BP. However, the responsive peptide is specifically tailored upon activation of autophagy, resulting in self-aggregation of BP residues which emit a 30-fold enhanced fluorescence. By measuring the intensity of fluorescent signal, we are able to quantitatively evaluate the autophagic level. In comparison with traditional techniques, such as TEM, Western blot, and GFP-LC3, the reliability and accuracy of this method are finally validated. We believe this in situ intracellular self-assembly strategy provides a rapid, effective, real-time, and quantitative method for monitoring autophagy in living objects, and it will be a useful tool for autophagy-related fundamental and clinical research.
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