Rational Design of Multi-Stimuli-Responsive Nanoparticles for Precise Cancer Therapy

Stimuli-responsive nanoparticles with target capacity are of great interest in drug delivery for cancer therapy. However, the challenge is to achieve highly smart release with precise spatiotemporal control for cancer therapy. Herein, we report the preparation and properties of multi-stimuli-responsive nanoparticles through the co-assembly of a 3-arm star quaterpolymer with a near-infrared (NIR) photothermal agent and chemotherapeutic compound. The nanoparticles can exhibit NIR light/pH/reduction–responsive drug release and intracellular drug translocation in cancer cells, which further integrate photoinduced hyperthermia for synergistic anticancer efficiency, thereby leading to tumor ablation without tumor regrowth. Thus, this rational design of nanoparticles with multiple responsiveness represents a versatile strategy to provide smart drug delivery paradigms for cancer therapy

Light-Responsive Nanoparticles for Highly Efficient Cytoplasmic Delivery of Anticancer Agents

Stimuli-responsive nanostructures have shown great promise for intracellular delivery of anticancer compounds. A critical challenge remains in the exploration of stimuli-responsive nanoparticles for fast cytoplasmic delivery. Herein, near-infrared (NIR) light-responsive nanoparticles were rationally designed to generate highly efficient cytoplasmic delivery of anticancer agents for synergistic thermo-chemotherapy. The drug-loaded polymeric nanoparticles of selenium-inserted copolymer (I/D-Se-NPs) were rapidly dissociated in several minutes through reactive oxygen species (ROS)-mediated selenium oxidation upon NIR light exposure, and this irreversible dissociation of I/D-Se-NPs upon such a short irradiation promoted continuous drug release. Moreover, I/D-Se-NPs facilitated cytoplasmic drug translocation through ROS-triggered lysosomal disruption and thus resulted in highly preferable distribution to the nucleus even in 5 min postirradiation, which was further integrated with light-triggered hyperthermia for achieving synergistic tumor ablation without tumor regrowth

Dual-Targeted Metal Ion Network Hydrogel Scaffold for Promoting the Integrated Repair of Tendon–Bone Interfaces

The tendon–bone interface has a complex gradient structure vital for stress transmission and pressure buffering during movement. However, injury to the gradient tissue, especially the tendon and cartilage components, often hinders the complete restoration of the original structure. Here, a metal ion network hydrogel scaffold, with the capability of targeting multitissue, was constructed through the photopolymerization of the LHERHLNNN peptide-modified zeolitic imidazolate framework-8 (LZIF-8) and the WYRGRL peptide-modified magnesium metal–organic framework (WMg-MOF) within the hydrogel scaffold, which could facilitate the directional migration of metal ions to form a dynamic gradient, thereby achieving integrated regeneration of gradient tissues. LZIF-8 selectively migrated to the tendon, releasing zinc ions to enhance collagen secretion and promoting tendon repair. Simultaneously, WMg-MOF migrated to cartilage, releasing magnesium ions to induce cell differentiation and facilitating cartilage regeneration. Infrared spectroscopy confirmed successful peptide modification of nano ZIF-8 and Mg-MOF. Fluorescence imaging validated that LZIF-8/WMg-MOF had a longer retention, indirectly confirming their successful targeting of the tendon–bone interface. In summary, this dual-targeted metal ion network hydrogel scaffold has the potential to facilitate synchronized multitissue regeneration at the compromised tendon–bone interface, offering favorable prospects for its application in the integrated reconstruction characterized by the gradient structure