Nanomedicines whose size can be varied on demand may synchronously achieve excellent tumor accumulation and penetration. In this study, by taking advantage of the pH sensitivity of a boronate ester, we synthesized acid-triggered size-reducing polymer nanoparticles (named PCD) by cross-linking β-cyclodextrin-cored multiarm polymers through the boronate ester. In PCD, the antitumor agent doxorubicin was loaded the pH-sensitive hydrazone linkage.
View Article and Find Full Text PDFPeptides and their conjugates are appealing as molecular scaffolds for constructing supramolecular biomaterials from the bottom up. Through strategic sequence design and interaction modulation, these peptides can self-assemble into diverse nanostructures that can, in turn, mimic the structural and catalytic functions of contemporary proteins. Here, inspired by the histidine brace active site identified in the metalloenzyme, we developed a triblock polypeptide with a hydrophobic polyleucine segment, a hydrophilic polylysine segment, and a terminal oligohistidine segment.
View Article and Find Full Text PDFPhotodynamic therapy (PDT) emerges as a promising strategy for combating bacteria with minimal drug resistance. However, a significant hurdle lies in the ineffectiveness of most photosensitizers against Gram-negative bacteria, primarily attributable to their characteristic impermeable outer membrane (OM) barrier. To tackle this obstacle, we herein report an amphipathic peptide-photosensitizer conjugate (PPC) with intrinsic outer membrane disruption capability to enhance PDT efficiency against Gram-negative bacteria.
View Article and Find Full Text PDFAdv Healthc Mater
September 2024
This work reports a new concept of cancer mask in situ to alter the specific biological functions of cancer cells. Metastatic cancer cells are highly invasive in part due to the presence of the glycan matrix in the cell membrane. Using a rational designed bio-orthogonal reaction, the cancer cell surface is reconstructed in situ by incorporating endogenous polysialic acids in the glycan matrix on the cell membrane to form a mesh-like network, called cancer mask.
View Article and Find Full Text PDFThe miniaturization of biomedical microrobots is crucial for their applications. However, it is challenging to reduce their size while maintaining their biomedical functions. To resolve this contradiction, we propose a semiphysical design concept for developing miniaturized microrobots, in which invisible components such as light beams are utilized to replace most of the physical parts of a microrobot, thus minimizing its physical size without sacrificing its biomedical functions.
View Article and Find Full Text PDFTumor penetration is a critical determinant of the therapy efficacy of nanomedicines. However, the dense extracellular matrix (ECM) in tumors significantly hampers the deep penetration of nanomedicines, resulting in large drug-untouchable areas and unsatisfactory therapy efficacy. Herein, we synthesized a third-generation PAMAM-cored multiarm copolymer and modified the polymer with collagenase to enhance its tumor penetration.
View Article and Find Full Text PDFThe deposition of the extracellular matrix, especially collagen, and the elevated expression levels of reactive oxygen species, including HO, are the main features of fibrosis. Fibrosis can occur in many tissues, such as tumor and liver tissues. The deposition of collagen in the location of lesions not only leads to immunological rejection and supports liver fibrosis and tumor progression, but also provides unique physiological signals with the progression of fibrosis and tumor.
View Article and Find Full Text PDFWhile performing oxygen-related tumour treatments such as chemotherapy and photodynamic therapy, real-time monitoring hypoxia of tumour is of great value and significance. Here, we design a theranostic combination for light-activated ratiometric hypoxia imaging, hypoxia modulating and prodrug activation. This combination consisted of an oxygen-sensitive near-infrared-emitting ratiometric phosphorescence probe and a hypoxia-activated prodrug-loaded covalent organic framework.
View Article and Find Full Text PDFHydrogen sulfide (HS) has shown promise for gas therapy. However, it is still controversial whether HS can remodel the tumor microenvironment (TME) and induce robust antitumor immunity. Here, a tumor-targeting and TME-responsive "smart" lipid nanoparticle (-JK-PS-FA) is presented, which is capable of delivering and releasing HS specifically in tumor tissues for on-demand HS gas and photodynamic immunotherapy.
View Article and Find Full Text PDFThe active delivery of nanodrugs has been a bottleneck problem in nanomedicine. While modification of nanodrugs with targeting agents can enhance their retention at the lesion location, the transportation of nanodrugs in the circulation system is still a passive process. The navigation of nanodrugs with external forces such as magnetic field has been shown to be effective for active delivery, but the existing techniques are limited to specific materials like magnetic nanoparticles.
View Article and Find Full Text PDFBacterial infection poses a significant threat to human health, and the emergence of antibiotic-resistant strains has exacerbated the situation. Antimicrobial photodynamic therapy (aPDT) has emerged as a promising antibiotic-free treatment option that employs reactive oxygen species (ROS) to cause oxidative damage to bacteria and surrounding biomolecules for treating microbial infections. This review summarizes the recent progress in the development of organic photosensitizers, including porphyrins, chlorophyll, phenothiazines, xanthenes and aggregation-induced emission photosensitizers, for aPDT.
View Article and Find Full Text PDFThe early detection of cancers can significantly change outcomes even with existing treatments. However, ~50% of cancers still cannot be detected until they reach an advanced stage, highlighting the great challenges in the early detection. Here, an ultrasensitive deep near-infrared (dNIR) nanoprobe that is successively responsive to tumor acidity and hypoxia is reported.
View Article and Find Full Text PDFInflammation plays an important role in the occurrence and development of disease; dysregulation of inflammatory progression often leads to disease such as tissue sclerosis, cancers, stroke, etc. Optical imaging technology, due to its higher sensitivity and resolution, can provide finer images for the observation of inflammation. Many optical probes have been developed as contrast agents for optical imaging techniques in different diseases.
View Article and Find Full Text PDFACS Appl Bio Mater
June 2023
Size is one of the crucial factors influencing the biological properties of nanomedicines. However, the size control of nanomaterials is still very challenging, and the size effect on their biological properties is worth studying. Herein, we present the synthesis and size control of a series of multiarm block copolymers with the third-generation PAMAM (G3 PAMAM) as the core.
View Article and Find Full Text PDFAdjuvant whole-breast radiotherapy is essential for breast cancer patients who adopted breast-conserving surgery (BCS) to reduce the risk of local recurrences, which however suffer from large-area and highly destructive ionizing radiation-induced adverse events. To tackle this issue, an afterglow/photothermal bifunctional polymeric nanoparticle (APPN) is developed that utilizes nonionizing light for precise afterglow imaging-guided post-BCS adjuvant second near-infrared (NIR-II) photothermal therapy. APPN consists of a tumor cell targeting afterglow agent, which is doped with a NIR dye as an afterglow initiator and a NIR-II light-absorbing semiconducting polymer as a photothermal transducer.
View Article and Find Full Text PDFImmunotherapy has offered new opportunities to treat head and neck squamous cell carcinoma (HNSCC); however, its clinical applications are hindered by modest therapeutic outcomes and the "always-on" pharmacological activity of immunomodulatory agents. Strategies for precise spatiotemporal activation of antitumor immunity can tackle these issues but remain challenging. Herein, a semiconducting polymeric nanoagonist (SPNM) with in situ sono-activatable immunotherapeutic effects for precision sono-immunotherapy of HNSCC is reported.
View Article and Find Full Text PDFCancer theranostics that combines cancer diagnosis and therapy is a promising approach for personalized cancer treatment. However, current theranostic strategies suffer from low imaging sensitivity for visualization and an inability to target the diseased tissue site with high specificity, thus hindering their translation to the clinic. In this study, we have developed a tumor microenvironment-responsive hybrid theranostic agent by grafting water-soluble, low-fouling fluoropolymers to pH-responsive zeolitic imidazolate framework-8 (ZIF-8) nanoparticles by surface-initiated RAFT polymerization.
View Article and Find Full Text PDFUnimolecular polymer nanomaterials (UPNs) have well-defined structures, desirable stability and designable functional groups, and hence exhibit great application potential in drug delivery. However, the syntheses of UPNs are generally time-consuming and tedious, which greatly limit their applications. In this paper, we present the preparation of a β-cyclodextrin-cored star-shaped polymer with 21 poly(-butyl acrylate) arms.
View Article and Find Full Text PDFTumor vascular disrupting therapy has offered promising opportunities to treat cancer in clinical practice, whereas the overall therapeutic efficacy is notably limited due to the off-target effects and repeated dose toxicity of vascular disrupting agents (VDAs). To tackle this problem, a VDA-free biomimetic semiconducting polymer nanoparticle (SPN ) is herein reported for precise tumor vascular disruption through two-stage light manipulation. SPN consists of a semiconducting polymer nanoparticle as the photothermal agent camouflaged with platelet membranes that specifically target disrupted vasculature.
View Article and Find Full Text PDFIn recent years, tumor immunotherapy has achieved significant success in tumor treatment based on immune checkpoint blockers and chimeric antigen receptor T-cell therapy. However, about 70-80% of patients with solid tumors do not respond to immunotherapy due to immune evasion. Recent studies found that some biomaterials have intrinsic immunoregulatory effects, except serve as carriers for immunoregulatory drugs.
View Article and Find Full Text PDFIntegrating the imaging techniques of near-infrared fluorescence (NIRF) and photoacoustic (PA) can make up for each other and provide more useful medical information. Ratiometric imaging activated by disease-associated biomarkers can further augment imaging specificity. However, very few studies have employed the NIRF/PA dual-modal ratiometric imaging to improve the accuracy and specificity of disease diagnosis to date.
View Article and Find Full Text PDFACS Appl Bio Mater
December 2022
Fluorination has been widely applied to improving the properties of small-molecule drugs. However, relatively little is known about the effects of fluorination on the drug delivery property of nanomaterials. In this paper, we synthesized a fluoroalkane-modified cylindrical polymer brush (CPB) BCPB-F and an alkane-modified analogue BCPB-H.
View Article and Find Full Text PDFDue to their homing effects, cell and cell membrane-derived nanocarriers have been widely used to enhance drug target delivery. Inspired by the protein-anchored cell membrane architecture, we here report a tumor-targeted liposome, dtDLP, which was constructed through the electrostatic interaction between dendritic lipopeptide liposomes and a dual-targeted recombinant protein, achieving superior tumor homing, cellular endocytotic and penetration abilities. The dual-targeted recombinant protein consists of an anti-epidermal growth factor receptor single domain antibody and a peptide ligand for the integrin αβ.
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