Cascade-responsive size/charge bidirectional-tunable nanodelivery penetrates pancreatic tumor barriers.

The pancreatic tumor microenvironment presents multiple obstacles for polymer-based drug delivery systems, limiting tumor penetration and treatment efficacy. Here, we engineer a hyaluronidase/reactive oxygen species cascade-responsive size/charge bidirectional-tunable nanodelivery (btND, G/R@TKP/HA) for co-delivery of gemcitabine and KRAS siRNA, capable of navigating through tumor barriers and augmenting anticancer efficiency. When penetrating the tumor stroma barrier, the hyaluronic acid shell of the nanodelivery undergoes degradation by hyaluronidase in an extracellular matrix, triggering size tuning from large to small and charge tuning from negative to positive, thereby facilitating deeper penetration and cellular internalization.

AIE-based nanoaggregate tracker: high-fidelity visualization of lysosomal movement and drug-escaping processes.

High-fidelity imaging and long-term visualization of lysosomes are crucial for their functional evaluation, related disease detection and active drug screening. However, commercial aggregation-caused quenching probes are not conducive to precise lysosomal imaging because of their inherent drawbacks, like easy diffusion, short emission and small Stokes shift, let alone their long-term tracing due to rapid photobleaching. Herein we report a novel aggregation-induced emission (AIE)-based TCM-PI nanoaggregate tracker for direct visualization of lysosomes based on the building block of tricyano-methylene-pyridine (TCM), wherein introduced piperazine (PI) groups behave as targeting units to lysosomes upon protonation, and the self-assembled nanostructure contributes to fast endocytosis for enhanced targeting ability as well as extended retention time for long-term imaging.

Tumour targeted contrast enhanced ultrasound imaging dual-modal microbubbles for diagnosis and treatment of triple negative breast cancer.

At present, the treatment of triple negative breast cancer (TNBC) is a worldwide problem, urgently requiring early precise diagnosis and effective treatment methods. In our study, we designed a type of tumour targeted dual-modal microbubbles, paclitaxel (PTX)-loaded RGD-lipid microbubbles (PTX@RGD-MBs), combined with ultrasonic targeted microbubble destruction (UTMD) to precisely diagnose TNBC and to improve the curative effect. As the first-line drug, PTX, lacking specific tumour targeting and the ability to be effectively internalized by TNBC cells, is still not effective in killing TNBC cells.