Wood structure-inspired injectable lignin-based nanogels as blood-vessel-embolic sustained drug-releasing stent for interventional therapies on liver cancer.

An embolic reagent with easy injection, well-controlled target embolization, and sustained release of chemotherapy drugs is urgently needed for successful trans-arterial chemo-embolization (TACE) treatment. However, the development of a highly effective embolic reagent is still challenged. Here, inspired and guided by the structural supporting properties and defense mechanisms of wood cell walls, an ideal lignin-based embolic nanogel (DOX-pN-KL) was explored. Based on the mechanical support of branched lignin and the π-π stacking force between the lignin aromatic ring with anti-tumor drug doxorubicin (DOX), DOX-pN-KL showed the highest mechanical strength among the reported thermosensitive embolization nanogel and performed high drug-loading and favorable sustained-release. Moreover, further TACE treatment and tumor microenvironment evaluation of VX2 tumor-bearing rabbits showed that this nanogel can completely block all levels of vessels in long term and continuously release DOX, thus having effective inhibition on tumor growth and metastasis. DOX-pN-KL is expected to be a promising alternative reagent for interventional therapy.

Radiofrequency-Activated Pyroptosis of Bi-Valent Gold Nanocluster for Cancer Immunotherapy.

Pyroptosis is gasdermin-mediated programmed necrosis that exhibits promising potential application in cancer immunotherapy, and the main challenge lies in how to provoke specific pyroptosis of tumor cells. Here, biGC@PNA with a precisely stoichiometric ratio of Au(I) ion/Au(0) atom induced pyroptosis of tumor cells by its radiofrequency (RF)-heating effect. An in vitro/in vivo assay on 4T1 tumor cells indicates RF-activated pyroptosis of tumor cells elicits a robust ICD effect, enhancing the synergistic antitumor efficacy of biGC@PNA with decitabine, significantly suppressing tumor metastasis and relapse by provoking systemic antitumor immune responses. Utilizing RF-activated pyroptotic immune responses, biGC@PNA efficiently enhances the antitumor efficacy of αPD-1 immunotherapy under RF irradiation and provides a promising strategy for improving cancer immunotherapy by the noninvasive RF field with high clinical transformation potential.

NIR-triggered ligand-presenting nanocarriers for enhancing synergistic photothermal-chemotherapy.

Surface PEGylation of nanomedicine is effective for prolonging blood circulation time and facilitating the EPR effect, whereas the hydrophilic stealth surface inhibits effective cellular uptake and hinders active targeting. To address the dilemma, herein, a NIR light-triggered dePEGylation/ligand-presenting strategy based on thermal decomposition of azo bonds is developed, whereby Dox/Pz-IR nanoparticle is self-assembled from thermo-labile azo molecule-linked long PEG chain polymer (Pz-IR), cRGD-conjugated IR783 with short PEG chains (rP-IR) and doxorubicin. The long PEG chains could mask cRGD peptides in the blood circulation, preventing serum degradation and nonspecific interaction with normal cells. Once exposed to NIR laser, the PEG corona is stripped off owing to the rupture of azo bonds through the photothermal effect of IR783, and the masked cRGD peptides are exposed, which remarkably enhances cellular uptake by tumor cells and improves tumor accumulation. Dox/Pz-IR achieves the optimal synergy of photothermal-chemotherapy at mild temperature through progressive tumor accumulation, precisely regulated photothermal effect and NIR-PTT induced pulsated drug release. The strategy of NIR photo-driven dePEGylation/targeting offers a new approach to overcoming the "PEG dilemma", and provides a noval avenue for programmed tumor-targeted drug delivery.

Calorimetric lateral flow immunoassay detection platform based on the photothermal effect of gold nanocages with high sensitivity, specificity, and accuracy.

BACKGROUND: Lateral flow assays (LFA) play an increasingly important role in the rapid detection of various pathogens, pollutants, and toxins. PURPOSE: To overcome the drawbacks of low sensitivity and poor quantification in LFA, we developed a new calorimetric LFA (CLFA) using gold nanocages (GNCs) due to their high photothermal conversion efficiency, good stability of photophysical properties, and stronger penetrating ability of NIR light. METHODS: Thiol-polyethylene glycol-succinyl imide ester (HS-PEG-NHS) was modified onto GNCs, and the complex was conjugated with an antibody. Subsequently, the antibody-conjugated GNCs were analyzed by UV/Vis spectrophotometer, transmission electron microscope, high-resolution transmission electron microscope with energy dispersive spectrometer, dynamic light scattering instrument, and Atom force microscope. The GNC-based CLFA of alpha-fetoprotein (AFP) and zearalenone (ZEN), a food toxin, required nitrocellulose strips, a NIR laser source, and an infrared camera. RESULTS: The GNC-labeled CLFA platform technique exhibited detection sensitivity, qualitative specificity, and quantitative accuracy. The superior performance of the technique was evident both in sandwich format detection of biomacromolecules (eg, AFP protein) or competitive format detection of small molecules (eg, ZEN). After optimizing various test parameters, GNC-labeled CLFA provided ca. 5-6-fold enhanced sensitivity, higher correlativity (R 2>0.99), and more favorable recovery (82-115%) when compared with visual LFA. CONCLUSION: GNC-labeled CLFA may be a promising detection platform with high sensitivity, specificity, and precision.

Rational design of temperature-sensitive blood-vessel-embolic nanogels for improving hypoxic tumor microenvironment after transcatheter arterial embolization.

Transcatheter arterial embolization (TAE) plays an important role in clinical tumor therapy by accomplishing vessel-casting embolization of tumor arteries at all levels and suppressing tumor collateral circulation and vascular re-canalization. In this study, we describe smart blood-vessel-embolic nanogels for improving the anti-tumor efficacy of TAE therapy on hepatocellular carcinoma (HCC). Methods: In this study, an in vitro model composed of two microfluidic chips was used for simulating the tumor capillary network and analyzing artery-embolization properties. Also, blood-vessel-casting embolization of renal arteries was evaluated in normal rabbits. Using a VX2 tumor-bearing rabbit model, the therapeutic efficacy of TAE on HCC was investigated for tumor growth, necrosis, and proliferation. Neovascularization and collateral circulation were evaluated by immunofluorescent detection of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and CD31 following the TAE therapy of VX2 tumor-bearing rabbits. Results: Sufficient embolization of all eight levels of micro-channels was achieved in a tumor-vessel-mimetic model with two microfluidic chips using PIBI-2240, and was further confirmed in renal arteries of normal rabbit. Effective inhibition of tumor collateral circulation and vascular re-canalization was observed in VX2 tumor-bearing rabbits due to the reduced expression levels of HIF-1α, VEGF, and CD31. Conclusions: The exceptional anti-tumor effect of PIBI-2240 observed in this study suggested that it is an excellent blood-vessel-embolic material for tumor TAE therapy.