Modalities for photo‐triggered anticancer therapy are usually limited by their low penetrative depth. Sonotheranostics especially sonodynamic therapy (SDT), which is different from photodynamic ...therapy (PDT) by the use of highly penetrating acoustic waves to activate a class of sound‐responsive materials called sonosensitizers, has gained significant interest in recent years. The effect of SDT is closely related to the structural and physicochemical properties of the sonosensitizers, which has led to the development of new sound‐activated materials as sonosensitizers for various biomedical applications. This Review provides a summary and discussion of the types of novel sonosensitizers developed in the last few years and outlines their specific designs and the potential challenges. The applications of sonosensitizers with various functions such as for imaging and drug delivery as well as in combination with other treatment modalities would provide new strategies for disease therapy.
A sound approach: Photo‐triggered anticancer therapeutic modalities are usually limited by their low penetrative depth. An alternative approach is sonodynamic therapy (SDT), which uses high‐penetrating acoustic waves to activate sound‐responsive materials. This Review gives a summary and discussion of such sonosensitizers.
Immunogenic cell death (ICD) and tumour-infiltrating T lymphocytes are severely weakened by elevated reactive oxygen species (ROS) in the tumour microenvironment. It is therefore of critical ...importance to modulate the level of extracellular ROS for the reversal of immunosuppressive environment. Here, we present a tumour extracellular matrix (ECM) targeting ROS nanoscavenger masked by pH sensitive covalently crosslinked polyethylene glycol. The nanoscavenger anchors on the ECM to sweep away the ROS from tumour microenvironment to relieve the immunosuppressive ICD elicited by specific chemotherapy and prolong the survival of T cells for personalized cancer immunotherapy. In a breast cancer model, elimination of the ROS in tumour microenvironment elicited antitumour immunity and increased infiltration of T lymphocytes, resulting in highly potent antitumour effect. The study highlights a strategy to enhance the efficacy of cancer immunotherapy by scavenging extracellular ROS using advanced nanomaterials.Reactive oxygen species in the tumour microenvironment can have an immunosuppressive effect. Here, the authors devise a nanoparticle that anchors to the extracellular matrix within tumours and scavenges reactive oxygen species, resulting in an enhanced immune response within the tumour.
We report the development of bioconjugated plasmonic vesicles assembled from SERS-encoded amphiphilic gold nanoparticles for cancer-targeted drug delivery. This new type of plasmonic assemblies with ...a hollow cavity can play multifunctional roles as delivery carriers for anticancer drugs and SERS-active plasmonic imaging probes to specifically label targeted cancer cells and monitor intracellular drug delivery. We have shown that the pH-responsive disassembly of the plasmonic vesicle, stimulated by the hydrophobic-to-hydrophilic transition of the hydrophobic brushes in acidic intracellular compartments, allows for triggered intracellular drug release. Because self-assembled plasmonic vesicles exhibit significantly different plasmonic properties and greatly enhanced SERS intensity in comparison with single gold nanoparticles due to strong interparticle plasmonic coupling, disassembly of the vesicles in endocytic compartments leads to dramatic changes in scattering properties and SERS signals, which can serve as independent feedback mechanisms to signal cargo release from the vesicles. The unique structural and optical properties of the plasmonic vesicle have made it a promising platform for targeted combination therapy and theranostic applications by taking advantage of recent advances in gold nanostructure based in vivo bioimaging and photothermal therapy and their loading capacity for both hydrophilic (nucleic acids and proteins) and hydrophobic (small molecules) therapeutic agents.
Vesicular structures with compartmentalized, water-filled cavities, such as liposomes of natural and synthetic amphiphiles, have tremendous potential applications in nanomedicine. When block ...copolymers self-assemble, the result is polymersomes with tailored structural properties and built-in releasing mechanisms, controlled by stimuli-responsive polymer building blocks. More recently, chemists are becoming interested in multifunctional hybrid vesicles containing inorganic nanocrystals with unique optical, electronic, and magnetic properties. In this Account, we review our recent progress in assembling amphiphilic plasmonic nanostructures to create a new class of multifunctional hybrid vesicles and applying them towards cancer diagnosis and therapy. Localized surface plasmon resonance (LSPR) gives plasmonic nanomaterials a unique set of optical properties that are potentially useful for both biosensing and nanomedicine. For instance, the strong light scattering at their LSPR wavelength opens up the applications of plasmonic nanostructures in single particle plasmonic imaging. Their superior photothermal conversion properties, on the other hand, make them excellent transducers for photothermal ablation and contrast agents for photoacoustic imaging. Of particular note for ultrasensitive detection is that the confined electromagnetic field resulting from excitation of LSPR can give rise to highly efficient surface enhanced Raman scattering (SERS) for molecules in close proximity. We have explored several ways to combine well-defined plasmonic nanocrystals with amphiphilic polymer brushes of diverse chemical functionalities. In multiple systems, we have shown that the polymer grafts impart amphiphilicity-driven self-assembly to the hybrid nanoparticles. This has allowed us to synthesize well-defined vesicles in which we have embedded plasmonic nanocrystals in the shell of collapsed hydrophobic polymers. The hydrophilic brushes extend into external and interior aqueous environment to stabilize the vesicular structure. More importantly, we have demonstrated that strong interparticle coupling greatly enhances the optical properties (scattering, photothermal conversion, and SERS) in plasmonic vesicles. In combination with the loading capacity of the vesicles, this technology can provide unique opportunities for integrated diagnosis and therapy, multimodality combination therapy, and imaging-guided therapy. One key property differentiating the plasmonic vesicles from other vesicular structures containing nanocrystals is that we can tailor the interparticle coupling and disintegration of the plasmonic vesicles by altering structural parameters and conformational changes of the covalently bound polymer brushes. This gives us tremendous flexibility to engineer plasmonic vesicles for ultrasensitive detection and targeted therapy. Through bringing together advances in nanochemistry, polymer chemistry, self-assembly, and nanophotonics, we expect to further expand our capability of tailoring optical and structural characteristics of plasmonic vesicles to address challenges in medical settings.
Exploring and understanding biological and pathological changes are of great significance for early diagnosis and therapy of diseases. Optical sensing and imaging approaches have experienced major ...progress in this field. Particularly, an emergence of various functional optical nanoprobes has provided enhanced sensitivity, specificity, targeting ability, as well as multiplexing and multimodal capabilities due to improvements in their intrinsic physicochemical and optical properties. However, one of the biggest challenges of conventional optical nanoprobes is their absolute intensity-dependent signal readout, which causes inaccurate sensing and imaging results due to the presence of various analyte-independent factors that can cause fluctuations in their absolute signal intensity. Ratiometric measurements provide built-in self-calibration for signal correction, enabling more sensitive and reliable detection. Optimizing nanoprobe designs with ratiometric strategies can surmount many of the limitations encountered by traditional optical nanoprobes. This review first elaborates upon existing optical nanoprobes that exploit ratiometric measurements for improved sensing and imaging, including fluorescence, surface enhanced Raman scattering (SERS), and photoacoustic nanoprobes. Next, a thorough discussion is provided on design strategies for these nanoprobes, and their potential biomedical applications for targeting specific biomolecule populations (e.g. cancer biomarkers and small molecules with physiological relevance), for imaging the tumor microenvironment (e.g. pH, reactive oxygen species, hypoxia, enzyme and metal ions), as well as for intraoperative image guidance of tumor-resection procedures.
Ferroptosis, a new form of regulated cell death that is iron‐ and reactive oxygen species dependent, has attracted much attention in the research communities of biochemistry, oncology, and especially ...material sciences. Since the first demonstration in 2012, a series of strategies have been developed to induce ferroptosis of cancer cells, including the use of nanomaterials, clinical drugs, experimental compounds, and genes. A plethora of research work has outlined the blueprint of ferroptosis as a new option for cancer therapy. However, the published ferroptosis‐related reviews have mainly focused on the mechanisms and pathways of ferroptosis, which motivated this contribution to bridge the gap between biological significance and material design. Therefore, it is timely to summarize the previous efforts on the emerging strategies for inducing ferroptosis and shed light on future directions for using such a tool to fight against cancer. Here, the current strategies of cancer therapy based on ferroptosis will be elaborated, the design considerations and the advantages and limitations are highlighted, and finally a future perspective on this emerging field is given.
Iron‐ and indirect iron‐based nanomaterials can be developed for ferroptosis‐based cancer therapy via release of their own iron or loaded endogenous iron in lysosomes after endocytosis, which can employ the Fenton reaction to produce reactive oxygen species and induce lipid peroxidation. Such systems are reviewed for application in cancer therapy.
The design of bright NIR‐II luminescent nanomaterials that enable efficient labelling of proteins without disturbing their physiological properties in vivo is challenging. We developed an efficient ...strategy to synthesize bright NIR‐II gold nanoclusters (Au NCs) protected by biocompatible cyclodextrin (CD). Leveraging the ultrasmall size of Au NCs (<2 nm) and strong macrocycle‐based host–guest chemistry, the as‐synthesized CD‐Au NCs can readily label proteins/antibodies. Moreover, the labelled proteins/antibodies enable highly efficient in vivo tracking during blood circulation, without disturbing their biodistribution and tumor targeting ability, thus leading to a sensitive tumor‐targeted imaging. CD‐Au NCs are stable in the harsh biological environment and show good biocompatibility and high renal clearance efficiency. Therefore, the NIR‐II biolabels developed in this study provide a promising platform to monitor the physiological behavior of biomolecules in living organisms.
Bright NIR‐II Au nanoclusters (NCs) were rationally synthesized by using biocompatible cyclodextrin (CD) as the ligands. The renal‐clearable CD‐Au NCs can readily label proteins/antibodies via strong macrocycle‐based host–guest chemistry and enable highly efficient in vivo tracking during blood circulation, without disturbing their biodistribution and tumor targeting ability, thus leading to a sensitive tumor‐targeted NIR‐II visualization.
Chemodynamic therapy (CDT) utilizes iron‐initiated Fenton chemistry to destroy tumor cells by converting endogenous H2O2 into the highly toxic hydroxyl radical (.OH). There is a paucity of ...Fenton‐like metal‐based CDT agents. Intracellular glutathione (GSH) with .OH scavenging ability greatly reduces CDT efficacy. A self‐reinforcing CDT nanoagent based on MnO2 is reported that has both Fenton‐like Mn2+ delivery and GSH depletion properties. In the presence of HCO3−, which is abundant in the physiological medium, Mn2+ exerts Fenton‐like activity to generate .OH from H2O2. Upon uptake of MnO2‐coated mesoporous silica nanoparticles (MS@MnO2 NPs) by cancer cells, the MnO2 shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn2+, resulting in GSH depletion‐enhanced CDT. This, together with the GSH‐activated MRI contrast effect and dissociation of MnO2, allows MS@MnO2 NPs to achieve MRI‐monitored chemo–chemodynamic combination therapy.
Self‐reinforcing weapon: The Fenton‐like Mn2+ delivery and glutathione (GSH) depletion abilities of MnO2 allow it to exert enhanced chemodynamic efficacy in cancer treatment. An activatable theranostic platform based on multifunctional MnO2‐coated mesoporous silica nanoparticles (MS@MnO2 NPs) has been developed for MRI‐monitored combination chemotherapy and chemodynamic therapy (CDT). ADS=antioxidant defense system.
The use of hydrogel‐based bone adhesives has the potential to revolutionize the clinical treatment of bone repairs. However, severe deficiencies remain in current products, including cytotoxicity ...concerns, inappropriate mechanical strength, and poor fixation performance in wet biological environments. Inspired by the unique roles of glue molecules in the robust mechanical strength and fracture resistance of bone, a design strategy is proposed using novel mineral–organic bone adhesives for strong water‐resistant fixation and guided bone tissue regeneration. The system leveraged tannic acid (TA) as a phenolic glue molecule to spontaneously co‐assemble with silk fibroin (SF) and hydroxyapatite (HA) in order to fabricate the inorganic–organic hybrid hydrogel (named SF@TA@HA). The combination of the strong affinity between SF and TA along with sacrificial coordination bonds between TA and HA significantly improves the toughness and adhesion strength of the hydrogel by increasing the amount of energy dissipation at the nanoscale. This in turn facilitated adequate and stable fixation of bone fracture in wet biological environments. Furthermore, SF@TA@HA promotes the regeneration of bone defects at an early stage in vivo. This work presents a type of bioinspired bone adhesive that is able to provide stable fracture fixation and accelerated bone regeneration during the bone remodeling process.
A biocompatible and high‐performance bone adhesive is developed for fracture fixation and healing in wet biological environments via mimicking the critical role of glue molecules in natural bone. The system leverages tannic acid as a phenolic glue molecule to co‐assemble with inorganic mineral and organic protein for achieving high strength and fracture toughness.
PDF
