Mn2+ /Ir3+ -Doped and CaCO3 -Covered Prussian Blue Nanoparticles with Indocyanine Green Encapsulation for Tumor Microenvironment Modulation and Image-Guided Synergistic Cancer Therapy.

The development of smart theranostic nanoplatforms has gained great interest in effective cancer treatment against the complex tumor microenvironment (TME), including weak acidity, hypoxia, and glutathione (GSH) overexpression. Herein, a TME-responsive nanoplatform named PMICApt /ICG, based on PB:Mn&Ir@CaCO3 Aptamer /ICG, is designed for the competent synergistic photothermal therapy and photodynamic therapy (PDT) under the guidance of photothermal and magnetic resonance imaging. The nanoplatform's aptamer modification targeting the transferrin receptor and the epithelial cell adhesion molecule on breast cancer cells, and the acid degradable CaCO3 shell allow for effective tumor accumulation and TME-responsive payload release in situ. The nanoplatform also exhibits excellent PDT properties due to its ability to generate O2 and consume antioxidant GSH in tumors. Additionally, the synergistic therapy is achieved by a single wavelength of near-infrared laser. RNA sequencing is performed to identify differentially expressed genes, which show that the expressions of proliferation and migration-associated genes are inhibited, while the apoptosis and immune response gene expressions are upregulated after the synergistic treatments. This multifunctional nanoplatform that responds to the TME to realize the on-demand payload release and enhance PDT induced by TME modulation holds great promise for clinical applications in tumor therapy.

Facile one-step synthesis of NIR-Responsive siRNA-Inorganic hybrid nanoplatform for imaging-guided photothermal and gene synergistic therapy.

Diagnosis-guided synergistic treatment based on innovative nanomaterials is of great significance for the development of anti-cancer therapies. However, the low delivery efficiency of therapeutic gene and the inability to trigger release on demand are still major obstacles impeding its wide application. Herein, we report an ultra-fast one-step method within 2 min to prepare a smart carrier, liposome-coated Prussian blue @ gold nano-flower, which is named LPAR after linking with tumor-targeting peptide. The versatile LPAR not only can respond to near-infrared (NIR) light, achieve the selective delivery and the controlled release of siRNA targeting the mutant gene of Kras at its codon-12 from Glycine (G) to Aspartic acid (D) (named as G12D mutant gene) in the malignant pancreatic tumors, but also efficiently convert the absorbed NIR light into the heat to realize gene-photothermal synergistic therapy both in vitro and in vivo. Theoretical simulation results reveal that the outstanding photothermal conversion efficiency of LPAR is mainly due to its higher electric field intensity and power density distributions. Furthermore, the LPAR possesses the capabilities for triple-modal imaging. Therefore, the developed NIR light-responsive LPAR has the potential to be served as a tumor-targeted nano-delivery system for imaging-guided synergistic therapy of cancers.

Protein-Inorganic Hybrid Nanoflowers as Efficient Biomimetic Antibiotics in the Treatment of Bacterial Infection.

Nanozymes have been developed as new generation of biomimetic antibiotics against wound infection. However, most of new-developed nanozymes based on inorganic particles or hybrid ones usually originate from incompatible raw materials or unwanted metal salts, highly limiting their further biomedical usages. To overcome above drawbacks, it is highly required to develop novel nanozymes with great antibacterial activity by using biocompatible reagents and endogenous metal species as raw materials. Here, we demonstrated that bovine serum albumin enwrapped copper phosphate-based protein-inorganic hybrid nanoflowers possessed intrinsic peroxidase-like activity, which could be used as efficient biomimetic antibiotics against bacterial infection via the nanozyme-mediated generation of high toxic reactive oxygen species (ROS). With the admirable peroxidase-like activity, our nanoflowers could efficiently kill drug-resistance bacteria under physiological conditions, improve the wound healing after pathogen-induced infection, as well as avoid the potential tissue injury in time. Comprehensive toxicity exploration of these nanoflowers indicated their high biocompatibility and excellent biosafety. Our current strategy toward the design of protein-inorganic hybrid nanozymes with high biosafety and few side effects could provide a new paradigm for the development of nanozyme-based antibacterial platform in future.