Residence structures, systems, and related methods are generally provided. Certain embodiments comprise administering (e.g., orally) a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. The residence structure may be, in some cases, a gastric residence structure. In some embodiments, the structures and systems described herein comprise one or more materials configured for high levels of active substances (e.g., a therapeutic agent) loading, high active substance and/or structure stability in acidic environments, mechanical flexibility and strength in an internal orifice (e.g., gastric cavity), easy passage through the GI tract until delivery to at a desired internal orifice (e.g., gastric cavity), and/or rapid dissolution/degradation in a physiological environment (e.g., intestinal environment) and/or in response to a chemical stimulant (e.g., ingestion of a solution that induces rapid dissolution/degradation). In certain embodiments, the structure has a modular design, combining a material configured for controlled release of therapeutic, diagnostic, and/or enhancement agents with a structural material necessary for gastric residence but configured for controlled and/or tunable degradation/dissolution to determine the time at which retention shape integrity is lost and the structure passes out of the gastric cavity. For example, in certain embodiments, the residence structure comprises a first elastic component, a second component configured to release an active substance (e.g., a therapeutic agent), and, optionally, a linker. In some such embodiments, the linker may be configured to degrade such that the residence structure breaks apart and is released from the location internally of the subject after a predetermined amount of time.

The present disclosure discloses preparation and application of a novel multifunctional nanocomposite material with new photosensitizer, and belongs to the technical field of photodynamic therapy and the field of biomedicine. The photosensitizer multifunctional nanocomposite material provided by the present disclosure is prepared by self-assembly of cercosporin and an acid-sensitive copolymer multifunctional material with liver tumor cell targeting ability and traceability, wherein the acid-sensitive copolymer multifunctional material can be a copolymer of poly(N,N-dimethylaminoethyl methacrylate) and poly-3-azido-2-hydroxypropyl methacrylate covalently linked by galactose-modified rhodamine B. The photosensitizer multifunctional nanocomposite material disclosed by the present disclosure can specifically recognize liver tumor cells and be endocytosed into the cells through galactose-asialoglycoprotein receptor interaction, and can trigger the release of the photosensitizer cercosporin under acidic pH conditions to exert photodynamic therapy efficiency. The novel photosensitizer multifunctional nanocomposite material has a good application prospect in targeted photodynamic therapy of tumor cells.

Embodiments of systems, methods, and compositions provided herein relate to hollow beads encapsulating single cells. Some embodiments include performing multiple co-assays on a single cell encapsulated within a hollow bead, including nucleic acid sequencing, preparing nucleic acid libraries, determining methylation status, identifying genomic variants, or protein analysis.

Embodiments of systems, methods, and compositions provided herein relate to hollow beads encapsulating single cells. Some embodiments include performing multiple co-assays on a single cell encapsulated within a hollow bead, including nucleic acid sequencing, preparing nucleic acid libraries, determining methylation status, identifying genomic variants, or protein analysis.

CNS metastases are a major cause of cancer deaths with few therapeutic options for treatment. Monoclonal anti-body-based therapy is one of the most successful therapeutic strategies for cancer; however, its efficacy is limited against CNS metastases due to insufficient CNS delivery. Here, we show significantly improved antibody delivery to the CNS using novel timed-release nanocapsules that encapsulate individual antibodies within a crosslinked phosphorylcholine polymer and gradually release cargo through hydrolysable crosslinkers. A single course of rituximab (RTX) nanocapsule treatment elevates RTX levels in the CNS by nearly 10-fold compared to native RTX. We improved control of CNS metastases in a murine xenograft model of non-Hodgkin lymphoma; moreover, using a xenograft humanized BLT mouse model, lymphomas were eliminated with a single course of RTX nanocapsule treatment. This approach is useful for treatment of cancers with CNS metastases and is generalizable for delivery of any antibody to the CNS.

CNS metastases are a major cause of cancer deaths with few therapeutic options for treatment. Monoclonal anti-body-based therapy is one of the most successful therapeutic strategies for cancer; however, its efficacy is limited against CNS metastases due to insufficient CNS delivery. Here, we show significantly improved antibody delivery to the CNS using novel timed-release nanocapsules that encapsulate individual antibodies within a crosslinked phosphorylcholine polymer and gradually release cargo through hydrolysable crosslinkers. A single course of rituximab (RTX) nanocapsule treatment elevates RTX levels in the CNS by nearly 10-fold compared to native RTX. We improved control of CNS metastases in a murine xenograft model of non-Hodgkin lymphoma; moreover, using a xenograft humanized BLT mouse model, lymphomas were eliminated with a single course of RTX nanocapsule treatment. This approach is useful for treatment of cancers with CNS metastases and is generalizable for delivery of any antibody to the CNS.

The present disclosure relates to a hypoxia-inducing cryogel, comprising one or more polymer and one or more hypoxia-inducing agent. The present disclosure additionally relates to a hypoxia-inducing construct, comprising a cryogel and a support. Methods of reducing concentration of oxygen in a medium, comprising contacting the medium with a hypoxia-inducing cryogel (HIC) or a hypoxia-inducing construct are disclosed. Additionally, methods of inducing hypoxia in a cell, comprising contacting the cell with a medium, wherein the medium comprises a HIC or a hypoxia-inducing construct are disclosed.

The present disclosure relates to a hypoxia-inducing cryogel, comprising one or more polymer and one or more hypoxia-inducing agent. The present disclosure additionally relates to a hypoxia-inducing construct, comprising a cryogel and a support. Methods of reducing concentration of oxygen in a medium, comprising contacting the medium with a hypoxia-inducing cryogel (HIC) or a hypoxia-inducing construct are disclosed. Additionally, methods of inducing hypoxia in a cell, comprising contacting the cell with a medium, wherein the medium comprises a HIC or a hypoxia-inducing construct are disclosed.

The invention is directed to extracellular matrix replacement (EMR)-drug conjugates, EMR-fluorescent label conjugates, EMR-cell compositions; to methods of making the EMR-drug conjugates, EMR-fluorescent label conjugates, or EMR-cell compositions; to pharmaceutical compositions comprising the EMR-drug conjugates, EMR-fluorescent label conjugates, or EMR-cell combinations; and to methods of treating wounds using the EMR-drug conjugates, EMR-fluorescent label conjugates, or EMR-cell compositions. The invention is also directed to cure-in-place (CIP) EMRs, to methods of making the CIP EMRs, to pharmaceutical compositions comprising the CIP EMRs, and methods of treating wounds using the CIP EMRs.

The disclosure describes poly(β-thioester) polymers and polymeric nanoparticles, pharmaceutical compositions comprising these materials, their use in the treatment of cancer and infectious disease, and machine learning methods for identifying and selecting them.