Effective endosomal escape remains as the "holy grail" for endocytosis-based intracellular drug delivery. To date, most of the endosomal escape strategies rely on small molecules, cationic polymers, or pore-forming proteins, which are often limited by the systemic toxicity and lack of specificity. We describe here a light-fueled liquid-metal transformer for effective endosomal escape-facilitated cargo delivery via a chemical-mechanical process. The nanoscale transformer can be prepared by a simple approach of sonicating a low-toxicity liquid-metal. When coated with graphene quantum dots (GQDs), the resulting nanospheres demonstrate the ability to absorb and convert photoenergy to drive the simultaneous phase separation and morphological transformation of the inner liquid-metal core. The morphological transformation from nanospheres to hollow nanorods with a remarkable change of aspect ratio can physically disrupt the endosomal membrane to promote endosomal escape of payloads. This metal-based nanotransformer equipped with GQDs provides a new strategy for facilitating effective endosomal escape to achieve spatiotemporally controlled drug delivery with enhanced efficacy.
DNA metallization has witnessed tremendous growth and development, from the initial simple synthesis aimed at manufacturing conductive metal nanowires to the current fabrication of various nanostructures for applications in areas as diverse as nanolithography, energy conversion and storage, catalysis, sensing, and biomedical engineering. To this, our aim here was to present a comprehensive review to summarize the research activities on DNA metallization that have appeared since the concept was first proposed in 1998. We start with a brief presentation of the basic knowledge of DNA and its unique advantages in the template-directed growth of metal nanomaterials, followed by providing a systematic summary of the various synthetic methods developed to date to deposit metals on DNA scaffolds. Then, the leverage of DNAs with different sequences, conformations, and structures for tuning the synthesis of feature-rich metal nanostructures is discussed. Afterwards, the discussion is divided around the applications of these metal nanomaterials in the fields mentioned above, wherein the key role DNA metallization plays in enabling high performance is emphasized. Finally, the current status and some future prospects and challenges in this field are summarized. As such, this review would be of great interest to promote the further development of DNA metallization by attracting researchers from various communities, including chemistry, biology, physiology, material science, and nanotechnology as well as other disciplines.
Nanomedicine development aims to enhance the efficacy, accuracy, safety, and/or compliance of diagnosis and treatment of diseases by leveraging the unique properties of engineered nanomaterials. To this end, a multitude of organic and inorganic nanoparticles have been designed to facilitate drug delivery, sensing, and imaging, some of which are currently in clinical trials or have been approved by the Food and Drug Administration (FDA). In the process, the increasing knowledge in understanding how natural particulates, including cells, pathogens, and organelles, interact with body and cellular systems has spurred efforts to mimic their morphology and functions for developing new generations of nanomedicine formulations. In addition, the advances in bioengineering tools, bioconjugation chemistries, and bio-nanotechnologies have further enabled researchers to exploit these natural particulates for theranostic purposes.
Radical surgery still represents the treatment choice for several malignancies. However, local and distant tumor relapses remain the major causes of treatment failure, indicating that a postsurgery consolidation treatment is necessary. Immunotherapy with checkpoint inhibitors has elicited impressive clinical responses in several types of human malignancies and may represent the ideal consolidation treatment after surgery. Here, we genetically engineered platelets from megakaryocyte (MK) progenitor cells to express the programmed cell death protein 1 (PD-1). The PD-1 platelet and its derived microparticle could accumulate within the tumor surgical wound and revert exhausted CD8 T cells, leading to the eradication of residual tumor cells. Furthermore, when a low dose of cyclophosphamide (CP) was loaded into PD-1-expressing platelets to deplete regulatory T cells (Tregs), an increased frequency of reinvigorated CD8 lymphocyte cells was observed within the postsurgery tumor microenvironment, directly preventing tumor relapse.
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