Prussian blue analog with separated active sites to catalyze water driven enhanced catalytic treatments.

Chemodynamic therapy (CDT) uses the Fenton or Fenton-like reaction to yield toxic ‧OH following H2O2 → ‧OH for tumoral therapy. Unfortunately, H2O2 is often taken from the limited endogenous supply of H2O2 in cancer cells. A water oxidation CoFe Prussian blue (CFPB) nanoframes is presented to provide sustained, external energy-free self-supply of ‧OH from H2O to process CDT and/or photothermal therapy (PTT). Unexpectedly, the as-prepared CFPB nanocubes with no near-infrared (NIR) absorption is transformed into CFPB nanoframes with NIR absorption due to the increased Fe3+-N ≡ C-Fe2+ composition through the proposed proton-induced metal replacement reactions. Surprisingly, both the CFPB nanocubes and nanoframes provide for the self-supply of O2, H2O2, and ‧OH from H2O, with the nanoframe outperforming in the production of ‧OH. Simulation analysis indicates separated active sites in catalyzation of water oxidation, oxygen reduction, and Fenton-like reactions from CFPB. The liposome-covered CFPB nanoframes prepared for controllable water-driven CDT for male tumoral mice treatments.

Atomically dispersed golds on degradable zero-valent copper nanocubes augment oxygen driven Fenton-like reaction for effective orthotopic tumor therapy.

Herein, we employ a galvanic replacement approach to create atomically dispersed Au on degradable zero-valent Cu nanocubes for tumor treatments on female mice. Controlling the addition of precursor HAuCl4 allows for the fabrication of different atomic ratios of AuxCuy. X-ray absorption near edge spectra indicates that Au and Cu are the predominant oxidation states of zero valence. This suggests that the charges of Au and Cu remain unchanged after galvanic replacement. Specifically, Au0.02Cu0.98 composition reveals the enhanced •OH generation following O2 → H2O2 → •OH. The degradable Au0.02Cu0.98 released Cu+ and Cu2+ resulting in oxygen reduction and Fenton-like reactions. Simulation studies indicate that Au single atoms boot zero-valent copper to reveal the catalytic capability of Au0.02Cu0.98 for O2 → H2O2 → •OH as well. Instead of using endogenous H2O2, H2O2 can be sourced from the O2 in the air through the use of nanocubes. Notably, the Au0.02Cu0.98 structure is degradable and renal-clearable.

Polyaniline-Based Glyco-Condensation on Au Nanoparticles Enhances Immunotherapy in Lung Cancer.

Lung cancer is considered among the deadliest cancers with a poor prognosis. Au@PG nanoparticles (NPs) are gold (Au)-based NPs featuring a polyaniline-based glyco structure (PG) generated from the polymerization of ortho-nitrophenyl-ß-d-galactopyranoside (ONPG) with promising M1 macrophage polarization activity, resulting in tumor remodeling and from a cold to a hot microenvironment, which promotes the cytotoxic T cell response and tumor inhibition. The combination of Au@PG NPs and anti-programmed cell death protein 1 (PD-1) therapy improved tumor inhibition and immunosuppression, accompanied by the secretion of immunogenic cytokines. A one-pot synthetic method was developed to achieve glyco-condensation during the formation of Au@PG NPs, which induced macrophage polarization more efficiently than Au@glucose, Au@mannose, and Au@galactose NPs. The switch from M2 to M1 macrophages was dependent on NP size, with smaller Au@PG NPs performing better than larger ones, with effectiveness ranked as follows: 32.2 nm ≈ 29.8 nm < 26.4 nm < 18.3 nm. Cellular uptake by endocytosis induced size-dependent endoplasmic reticulum (ER) stress, which resulted in the activation of spleen tyrosine kinase (SYK), leading to immune modulations and macrophage polarization. Our results suggested the promising potential of Au@PG NPs in lung cancer immunotherapy.

Chemical Structure and Shape Enhance MR Imaging-Guided X-ray Therapy Following Marginative Delivery.

Ineffective site-specific delivery has seriously impeded the efficacy of nanoparticle-based drugs to a disease site. Here, we report the preparation of three different shapes (sphere, scroll, and oblate) to systematically evaluate the impact of the marginative delivery on the efficacy of magnetic resonance (MR) imaging-guided X-ray irradiation at a low dose of 1 Gy. In addition to the shape effect, the therapeutic efficacy is investigated for the first time to be strongly related to the structure effect that is associated with the chemical activity. The enhanced particle-vessel wall interaction of both the flat scroll and oblate following margination dynamics leads to greater accumulation in the lungs, resulting in superior performance over the sphere against lung tumor growth and suppression of lung metastasis. Furthermore, the impact of the structural discrepancy in nanoparticles on therapeutic efficacy is considered. The tetragonal oblate reveals that the feasibility of the charge-transfer process outperforms the orthorhombic scroll and cubic sphere to suppress tumors. Finally, surface area is also a crucial factor affecting the efficacy of X-ray treatments from the as-prepared particles.

Synchronization of Nanoparticle Sensitization and Radiosensitizing Chemotherapy through Cell Cycle Arrest Achieving Ultralow X-ray Dose Delivery to Pancreatic Tumors.

Pancreatic cancer is among the leading causes of cancer-related death and remains a formidable therapeutic challenge. To date, surgical resection and chemotherapy have been the standards of care. Methotrexate (MTX), which is recognized as a refractory drug for pancreatic cells, was conjugated to the surface of LiYF4:Ce3+ nanoparticles (NP-MTX) through a photocleavable linker molecule. When LiYF4:Ce3+ NPs are stimulated by X-rays, they emit light, which induces the photocleavage of the photolabile linker molecule to release MTX. MTX can target pancreatic tumors, which overexpress folic acid (FA) receptors and are internalized into the cell through receptor-mediated endocytosis. The synergistic effect of the NP-MTX treatment initiated by X-ray irradiation occurs due to the combination of nanoparticle sensitization and the radiosensitizing chemotherapy of the photocleaved MTX molecule. This dual sensitization effect mediated by NP-MTX enabled 40% dose enhancement, which corresponded with an increase in the generation of cytotoxic cellular reactive oxygen species (ROS) and enhanced S phase arrest within the cell cycle. The delivery of an ultralow radiation dose of 0.1 Gy resulted in the photocleavage of MTX from NP-MTX, and this strategy demonstrated in vivo efficacy against AsPC-1 and PANC-1 xenografted pancreatic tumors.

1550 nm excitation-responsive upconversion nanoparticles to establish dual-photodynamic therapy against pancreatic tumors.

The second near-infrared biological window b (NIR-IIb, 1500-1700 nm) is recently considered as the promising region for deeper tissue penetration. Herein, a nanocarrier for 1550 nm light-responsive dual-photodynamic therapy (PDT) is developed to efficiently boost singlet oxygen (1O2) generation. The dual-photosensitizers (PSs), rose bengal (RB) and chlorin e6 (Ce6), are carried by the silica-coated core-shell LiYbF4:Er@LiGdF4 upconversion nanoparticles (UCNPs), forming UCNP/RB,Ce6. Following 1550 nm laser irradiation, the upconversion emission of UCNP/RB,Ce6 in both green (∼550 nm) and red (∼670 nm) colors is fully utilized to activate RB and Ce6, respectively. The simultaneous triggering of dual-PS generates an abundant amount of 1O2 resulting in boosted PDT efficacy. This dual-PDT nanocarrier presents an enhanced anticancer effect under single dose treatment in comparison with the single-PS ones from in vitro and in vivo treatments. The marriage between the boosted dual-PDT and 1550 nm light excitation is anticipated to provide a new avenue for non-invasive therapy.