Surface-Roughened SERS-Active Single Silver Nanowire for Simultaneous Detection of Intracellular and Extracellular pHs.

The simultaneous and accurate detection of intracellular pH (pHi) and extracellular pH (pHe) is essential for studying the complex physiological activities of cancer cells and exploring pH-related therapeutic mechanisms. Here, we developed a super-long silver nanowire-based surface-enhanced Raman scattering (SERS) detection strategy for simultaneous sensing of pHi and pHe. A surface-roughened silver nanowire (AgNW) with a high aspect ratio is prepared at a nanoelectrode tip using a Cu-mediated oxidation process, which is then modified by pH-sensitive 4-mercaptobenzoic acid (4-MBA) to form 4-MBA@AgNW as a pH sensing probe. With the assistance of a 4D microcontroller, 4-MBA@AgNW is efficient in simultaneously detecting pHi and pHe in both 2D and 3D culture cancer cells by SERS, with minimal invasiveness, high sensitivity, and spatial resolution. Further investigation proves that the surface-roughened single AgNW can also be used in monitoring the dynamic variation of pHi and pHe of cancer cells upon stimulation with anticancer drugs or under a hypoxic environment.

Engineered Platelet-Based Micro/Nanomotors for Cancer Therapy.

Engineered platelets (PLT) can bring new possibilities for diseases treatment due to the specific response for a variety of physiological disease environments. However, the deep penetration of engineered PLT in diseased tissues such as tumor is still an important challenge that restricts the therapeutic effect. Herein, the engineered PLT micromotor (PLT@PDA-DOX) is constructed by a universal self-polymerization modification method of dopamine, and the chemotherapeutic drug doxorubicin (DOX) is loaded by both π-π stacking interaction with polydopamine (PDA) and cellular endocytosis of PLT. The experimental results prove that PLT@PDA-DOX can target to tumor site by the specific binding of PLT with cancer cells, and then the secondary PLT-derived microparticles (PMP@PDA-DOX) are released with the activation of PLT@PDA-DOX by tumor microenvironment (TME). Besides, benefiting from the photothermal conversion capability of PDA, PLT@PDA-DOX micromotors and PMP@PDA-DOX nanomotors are driven by near-infrared light to realize deep penetration. And the PLT-based micro/nanomotors with propulsion capability possess good performance for tumor ablating in vitro and in vivo. In consideration of the operability, mildness, universality of this modification method and the good biocompatibility of PDA, this work may provide a general paradigm for the construction of engineered cells in disease treatment.

Platelet-derived porous nanomotor for thrombus therapy.

The treatment difficulties of venous thrombosis include short half-life, low utilization, and poor penetration of drugs at thrombus site. Here, we develop one kind of mesoporous/macroporous silica/platinum nanomotors with platelet membrane (PM) modification (MMNM/PM) for sequentially targeting delivery of thrombolytic and anticoagulant drugs for thrombus treatment. Regulated by the special proteins on PM, the nanomotors target the thrombus site and then PM can be ruptured under near-infrared (NIR) irradiation to achieve desirable sequential drug release, including rapid release of thrombolytic urokinase (3 hours) and slow release of anticoagulant heparin (>20 days). Meantime, the motion ability of nanomotors under NIR irradiation can effectively promote them to penetrate deeply in thrombus site to enhance retention ratio. The in vitro and in vivo evaluation results confirm that the synergistic effect of targeting ability from PM and motion ability from nanomotors can notably enhance the thrombolysis effect in both static/dynamic thrombus and rat model.

Systematic Research and Evaluation Models of Nanomotors for Cancer Combined Therapy.

Limited tumor permeability of therapeutic agents is a great challenge faced by current cancer therapy methods. Herein, a kind of near infrared light (NIR)-driven nanomotor with autonomous movement, targeted ability, hierarchical porous structure, multi-drugs for cancer chemo/photothermal therapy is designed, prepared and characterized. Further, we establish a method to study the interaction between nanomotors and cells, along with their tumor permeability mechanism, including 2D cellular models, 3D multicellular tumor spheroids and in vivo models. In vivo tumor elimination results verify that the movement behaviour of the nanomotors can greatly facilitate them to eliminate tumor through multiple therapeutic methods. This work tries to establish systematic research and evaluation models, providing strategies to understand the relationship between motion behaviour and tumor permeation efficiency of nanomotors in depth.