Nanoradiosentizers with X ray-actuatable supramolecular aptamer building units for programmable immunostimulatory T cell engagement.

The insufficient activation and impaired effector functions of T cells in the immunosuppressive tumor microenvironment (TME) substantially reduces the immunostimulatory effects of radiotherapy. Herein, a multifunctional nanoradiosensitizer is established by integrating molecularly engineered aptamer precursors into cisplatin-loaded liposomes for enhancing radio-immunotherapy of solid tumors. Exposure to ionizing radiation (IR) following the nanoradiosensitizer treatment would induce pronounced immunogenic death (ICD) of tumor cells through cisplatin-mediated radiosensitization while also trigger the detachment of the aptamer precursors, which further self-assemble into PD-L1/PD-1-bispecific aptamer-based T cell engagers (CA) through the bridging effect of tumor-derived ATP to direct T cell binding onto tumor cells in the post-IR TME in a spatial-temporally programmable manner.

Programmable melanoma-targeted radio-immunotherapy via fusogenic liposomes functionalized with multivariate-gated aptamer assemblies.

Radio-immunotherapy exploits the immunostimulatory features of ionizing radiation (IR) to enhance antitumor effects and offers emerging opportunities for treating invasive tumor indications such as melanoma. However, insufficient dose deposition and immunosuppressive microenvironment (TME) of solid tumors limit its efficacy. Here we report a programmable sequential therapeutic strategy based on multifunctional fusogenic liposomes (Lip@AUR-ACP-aptPD-L1) to overcome the intrinsic radio-immunotherapeutic resistance of solid tumors.

Inhibition of glycolysis-driven immunosuppression with a nano-assembly enhances response to immune checkpoint blockade therapy in triple negative breast cancer.

Immune-checkpoint inhibitors (ICI) are promising modalities for treating triple negative breast cancer (TNBC). However, hyperglycolysis, a hallmark of TNBC cells, may drive tumor-intrinsic PD-L1 glycosylation and boost regulatory T cell function to impair ICI efficacy. Herein, we report a tumor microenvironment-activatable nanoassembly based on self-assembled aptamer-polymer conjugates for the targeted delivery of glucose transporter 1 inhibitor BAY-876 (DNA-PAE@BAY-876), which remodels the immunosuppressive TME to enhance ICI response.

DNAzyme Nanoconstruct-Integrated Autonomously-Adaptive Coatings Enhance Titanium-Implant Osteointegration by Cooperative Angiogenesis and Vessel Remodeling.

Orthopedic implants have a high failure rate due to insufficient interfacial osseointegration, especially under osteoporotic conditions. Type H vessels are CD31EMCN capillaries with crucial roles in mediating new bone formation, but their abundance in osteoporotic fracture site is highly limited. Herein, we report a nanoengineered composite coating to improve the in situ osseointegration of a Ti implant for osteoporotic fracture repair, which is realized through inhibiting the stimulator of interferon genes (STING) in endothelial cells (ECs) to stimulate type H vessel formation.

A highly specific aptamer probe targeting PD-L1 in tumor tissue sections: Mutation favors specificity.

Although DNA aptamers can show comparable affinity to antibodies and have the advantage of having high batch-to-batch consistency, they often suffer from unsatisfied specificity for complex samples. The limited library size used for aptamer in vitro isolation (SELEX) has been recognized as one of the major reasons. Programmed cell death-ligand 1 (PD-L1) is both a key protein in cancer diagnostics and also immunotherapy.

PD-L1 aptamer isolation via Modular-SELEX and its applications in cancer cell detection and tumor tissue section imaging.

PD-1/PD-L1 is an important pathway in immunotherapy and a high PD-L1 expression level in tumor tissues is an essential prerequisite for PD-1/PD-L1 blocking-based therapy. The PD-L1 expression level in tumor tissue sections is currently detected via immunohistochemistry (IHC) using anti-PD-L1 antibodies from various resources, which has the disadvantage of inconsistent results. As synthetic affinity ligands, aptamers have good batch-to-batch consistency and have been demonstrated to have great potential for use in biomedical applications.

Speeding up in Vitro Discovery of Structure-Switching Aptamers via Magnetic Cross-Linking Precipitation.

We report here a modified aptamer selection method, magnetic cross-linking precipitation (MCP)-SELEX, for highly efficient library enrichment and aptamer isolation. MCP-SELEX isolates bound aptamers via highly efficient chemical cross-linking between amino groups of target proteins and activated carboxylic acid groups on magnetic beads (>90% coupling efficiency). Importantly, MCP-SELEX avoids surface interferences in conventional target-fixed methods and substantially minimizes nonspecific binding.