The encapsulation of molecular cargo within well-defined supramolecular architectures is highly challenging. Synthetic hosts are desirable because of their well-defined nature and addressability. Encapsulation of biomacromolecules within synthetic hosts is especially challenging because of the former's large size, sensitive nature, retention of functionality post-encapsulation and demonstration of control over the cargo. Here we encapsulate a fluorescent biopolymer that functions as a pH reporter within synthetic, DNA-based icosahedral host without molecular recognition between host and cargo. Only those cells bearing receptors for the DNA casing of the host–cargo complex engulf it. We show that the encapsulated cargo is therefore uptaken cell specifically in Caenorhabditis elegans. Retention of functionality of the encapsulated cargo is quantitatively demonstrated by spatially mapping pH changes associated with endosomal maturation within the coelomocytes of C. elegans. This is the first demonstration of functionality and emergent behaviour of a synthetic host–cargo complex in vivo.

Functionalization of quantum dots (QDs) with a single biomolecular tag using traditional approaches in bulk solution has met with limited success. DNA polyhedra consist of an internal void bounded by a well-defined three-dimensional structured surface. The void can house cargo and the surface can be functionalized with stoichiometric and spatial precision. Here, we show that monofunctionalized QDs can be realized by encapsulating QDs inside DNA icosahedra and functionalizing the DNA shell with an endocytic ligand. We deployed the DNA-encapsulated QDs for real-time imaging of three different endocytic ligands—folic acid, galectin-3 (Gal3) and the Shiga toxin B-subunit (STxB). Single-particle tracking of Gal3- or STxB-functionalized QD-loaded DNA icosahedra allows us to monitor compartmental dynamics along endocytic pathways. These DNA-encapsulated QDs, which bear a unique stoichiometry of endocytic ligands, represent a new class of molecular probes for quantitative imaging of endocytic receptor dynamics.

Nanotechnology has increasingly emerged as a promising tool for exploring new approaches, from treating complex conditions to early detection of the onset of multiple disease states.

Cancer is a highly heterogeneous disease and remains a global health challenge affecting millions of human lives worldwide. Despite advancements in conventional treatments like surgery, chemotherapy, and immunotherapy, the rise of multidrug resistance, tumor recurrence, and their severe side effects and the complex nature of the tumor microenvironment (TME) necessitates innovative therapeutic approaches. Recently, stimulus-responsive nanomedicines designed to target TME characteristics (e.g., pH alterations, redox conditions, enzyme secretion) have gained attention for their potential to enhance anticancer efficacy while minimizing the adverse effects of chemotherapeutics/bioactive compounds. Among the various nanocarriers, hydrogels are intriguing due to their high-water content, adjustable mechanical characteristics, and responsiveness to external and internal stimuli, making them promising candidates for cancer therapy. These properties make hydrogels an ideal nanocarrier for controlled drug release within the TME. This review comprehensively surveys the latest advancements in the area of stimulus-responsive hydrogels for cancer therapy, exploring various stimuli-responsive mechanisms, including biological (e.g., pH, redox), chemical (e.g., enzymes, glucose), and physical (e.g., temperature, light), as well as dual- or multi-stimuli responsiveness. Furthermore, this review addresses the current developments and challenges in hydrogels in cancer treatment. Our aim is to provide readers with a comprehensive understanding of stimulus-responsive hydrogels for cancer treatment, offering novel perspectives on their development for cancer therapy and other medical applications.