Achieving Immune Activation by Suppressing the IDO1 Checkpoint with Sono-Targeted Biobromination for Antitumor Combination Immunotherapy.

Indoleamine-2,3-dioxygenase-1 (IDO1) pathogenically suppresses immune cell infiltration and promotes tumor cell immune escape by overmetabolizing tryptophan to -formyl kynurenine in the tumor microenvironment (TME). However, it remains challenging for IDO1 immune checkpoint inhibitors to achieve a significant potency of progression-free survival. Here, we developed a breakthrough in IDO1 inhibition by sono-targeted biobromination reaction using immunostimulating hypobromic--phenylperoxydibenzoic acid-linked metallic organic framework nanomedicine (H-MOF NM) to remodel the TME from debrominated hypoxia into hypobromated normoxia and activate the IDO1 immune pathway with and remarkable antitumor efficacy.

Inhibition of thioredoxin reductase and upregulation of apoptosis genes for effective anti-tumor sono-chemotherapy using a -organosilica nanomedicine.

The thioredoxin system is involved in cancer development and therefore is a promising target for cancer chemotherapy. Thioredoxin reductase (TrxR) is a key component of the thioredoxin (Trx) system, and is overexpressed in many cancers to inhibit apoptosis-related proteins. Alternatively, inhibition of thioredoxin reductase and upregulation of apoptosis factors provide a therapeutic strategy for anti-tumor treatment.

Integrated organosilica nanomedicine enables sonoimaging, sonochemistry and antitumor sonodynamic therapy.

Sonography with its non-invasive and deep tissue-penetrating characteristics, not only contributes to promising developments in clinical disease diagnosis but also obtains acknowledgments as a prospective therapeutic approach in the field of tumor treatment. However, it remains a challenge for sonography simultaneously to achieve efficient imaging and therapeutic functionality. Here, we present an innovative integrated diagnosis and treatment paradigm by developing the nanomedicine of percarbamide-bromide-mesoporous organosilica spheres (MOS) with RGD peptide modification (PBMR) by loading percarbamide and bromide in MOS which were prepared by a one-step O/W microemulsion method.

Hydrogen Therapy Reverses Cancer-Associated Fibroblasts Phenotypes and Remodels Stromal Microenvironment to Stimulate Systematic Anti-Tumor Immunity.

Tumor microenvironment (TME) plays an important role in the tumor progression. Among TME components, cancer-associated fibroblasts (CAFs) show multiple tumor-promoting effects and can induce tumor immune evasion and drug-resistance. Regulating CAFs can be a potential strategy to augment systemic anti-tumor immunity.

Bimetallic Organic Frameworks of High Piezovoltage for Sono-Piezo Dynamic Therapy.

Piezoelectric materials produce charges to directly act on cancer medium or promote the generation of reactive oxygen species (ROS) for novel tumor therapy triggered by sonography. Currently, piezoelectric sonosensitizers are mainly used to catalyze ROS generation by the band-tilting effect for sonodynamic therapy. However, it remains a challenge for piezoelectric sonosensitizers to produce high piezovoltages to overcome the bandgap barrier for direct charge generation.

Polydopamine Nanoparticles Targeting Ferroptosis Mitigate Intervertebral Disc Degeneration Via Reactive Oxygen Species Depletion, Iron Ions Chelation, and GPX4 Ubiquitination Suppression.

Intervertebral disc degeneration (IVDD)-induced lower back pain (LBP) is a common problem worldwide. The underlying mechanism is partially accredited to ferroptosis, based on sequencing analyses of IVDD patients from the gene expression omnibus (GEO) databases. In this study, it is shown that polydopamine nanoparticles (PDA NPs) inhibit oxidative stress-induced ferroptosis in nucleus pulposus (NP) cells in vitro.

Prussian Blue Nanoparticles Stabilize SOD1 from Ubiquitination-Proteasome Degradation to Rescue Intervertebral Disc Degeneration.

Discography often destroys the hypoxic environment in the intervertebral disc and accelerates intervertebral disc degeneration (IVDD). Therefore, it often fails to meet the requirements for application in clinical practice. This technology mainly increases the reactive oxygen species (ROS) in the IVD.

Activatable nanomedicine for overcoming hypoxia-induced resistance to chemotherapy and inhibiting tumor growth by inducing collaborative apoptosis and ferroptosis in solid tumors.

Hypoxia has been firmly correlated to the drug resistance of solid tumors. Alleviation of hypoxia by tumor reoxygenation is expected to sensitize the chemotherapy toward solid tumors. Alternatively, ferroptosis provides a therapeutic strategy to overcome apoptotic resistance and multidrug resistance of solid tumors, collaboratively strengthening the chemotherapy toward hypoxic tumors.

An ultrasound activated oxygen generation nanosystem specifically alleviates myocardial hypoxemia and promotes cell survival following acute myocardial infarction.

Hypoxemia after acute myocardial infarction (AMI) causes severe damage to cardiac cells and induces cardiac dysfunction. Protection of cardiac cells and reconstruction of cardiac functions by re-introducing oxygen into the infarcted myocardium represents an efficient approach for the treatment of AMI. However, the established methods for oxygen supplementation mainly focus on systemic oxygen delivery, which always results in inevitable oxidative stress on normal tissues.

Ir/Cu Dual Catalysis: Enantio- and Diastereodivergent Access to α,α-Disubstituted α-Amino Acids Bearing Vicinal Stereocenters.

We describe a fully stereodivergent synthesis of a range of α,α-disubstituted α-amino acids via an Ir/Cu-catalyzed α-allylation of readily available imine esters. The introduction of a Cu-Phox complex-activated imine ester into the chiral iridium-catalyzed allylic allylation process is crucial for its high reactivity and excellent enantio- and diastereoselectivity (up to >99% ee and >20:1 dr). Importantly, the two chiral catalysts allow for full control over the configuration of the stereocenters, affording all stereoisomers of the desired products.

Pd/Cu dual catalysis: highly enantioselective access to α-substituted α-amino acids and α-amino amides.

The asymmetric allylation of glycine iminoesters has been accomplished through a synergistic Pd/Cu catalyst system, affording a range of α-substituted α-amino acids in high yields and with excellent enantioselectivities (88 → 99% ee). The introduction of a Cu-P,N-metallocenyl complex-activated glycine iminoester to the chiral palladium-catalyzed allylic allylation process is crucial owing to its high reactivity and excellent enantioselectivities. Importantly, this Pd/Cu dual catalysis strategy can be used for the asymmetric allylic alkylation of prochiral glycine amide derivatives, which could be further utilized to synthesize biologically important vicinal diamines.

Cooperative bimetallic catalysis in asymmetric allylic substitution.

Synergistic catalysis is gaining increasing attention due to its advantages over traditional catalytic methodologies, such as improved catalytic activity, broader substrate scope, increased selectivity and lower cost. Methodologies involving the synergistic combination of metal catalysts and organocatalysts have been intensively studied. Given the clear benefits of bimetallic catalyst systems consisting of two distinct metal catalysts, cooperative bimetallic catalysis has proved to be successful for a number of difficult asymmetric transformations.

Stereoselective and Site-Specific Allylic Alkylation of Amino Acids and Small Peptides via a Pd/Cu Dual Catalysis.

We report a stereoselective and site-specific allylic alkylation of Schiff base activated amino acids and small peptides via a Pd/Cu dual catalysis. A range of noncoded α,α-dialkyl α-amino acids were easily synthesized in high yields and with excellent enantioselectivities (up to >99% ee). Furthermore, a direct and highly stereoselective synthesis of small peptides with enantiopure α-alkyl or α,α-dialkyl α-amino acids residues incorporated at specific sites was accomplished using this dual catalyst system.

Direct use of allylic alcohols and allylic amines in palladium-catalyzed allylic amination.

Allylic alcohols and allylic amines were directly utilized in a Pd-catalyzed hydrogen-bond-activated allylic amination under mild reaction conditions in the absence of any additives. The cooperative action of a Pd-catalyst and a hydrogen-bonding solvent is most likely responsible for its high reactivity. The catalytic system is compatible with a variety of functional groups and can be used to prepare a wide range of linear allylic amines in good to excellent yields.

Lysosomes activating chain reactions against cancer cells with a pH-switched prodrug/procatalyst co-delivery nanosystem.

Conventional chemotherapy uses potent toxic drugs to destroy cancer cells and always causes severe systemic toxicity in patients. In this respect, a smart and pH-switched prodrug/procatalyst co-delivery nanosystem is developed which is non-toxic toward normal cells and is inert during its delivery in the vasculature, while responsively functions in acidic lysosomes inside cancer cells. Synthetically, non-toxic artemisinin (ART) was used as the prodrug and loaded into the inner space of hollow mesoporous silica (HMS) nanoparticles (NPs).

Efficient free radical generation against cancer cells by low-dose X-ray irradiation with a functional SPC delivery nanosystem.

Tumor hypoxia is a negative prognostic factor in cancer radiotherapy, due in part to its role in causing resistance to radiotherapy. It has attracted extensive critical attention to radiation sensitizers by using active oxygen to improve radiotherapy outcome. Active oxygen delivery functional materials are promising candidates to transport active oxygen to tumor cells.

Ultra-trace silver-doped hydroxyapatite with non-cytotoxicity and effective antibacterial activity.

Hydroxyapatite (HAp) nanocrystals as the main inorganic component in hard tissue have been extensively studied for bone regeneration and dental implant treatment. However, failure of surgical reconstruction often occurs owing to the lack of effective antibacterial ability of HAp. It is still a challenge to develop artificial HAp with both efficient antibacterial ability and proper biological properties.

Lysosome-controlled efficient ROS overproduction against cancer cells with a high pH-responsive catalytic nanosystem.

Excess reactive oxygen species (ROS) have been proved to damage cancer cells efficiently. ROS overproduction is thus greatly desirable for cancer therapy. To date, ROS production is generally uncontrollable and outside cells, which always bring severe side-effects in the vasculature.

Selective intracellular free radical generation against cancer cells by bioactivation of low-dose artesunate with a functionalized mesoporous silica nanosystem.

Excessive free radicals are noxious for living organisms and lead to cell death. Destruction of malignant cells by reactive free radicals has been widely used in cancer treatment. A key consideration is how to allow targeted free radical attack on cancer cells and avoid unwanted side-effects.

Controlled free radical generation against tumor cells by pH-responsive mesoporous silica nanocomposite.

Free radicals are toxic entities known to cause cellular damage and to mediate cell death. We herein develop a controlled free radical generation strategy for cancer therapy via pH-responsive release of benzoyl peroxide (BPO) in tumor cells and producing free radicals to mediate cell death. BPO as the free radical resource was encapsulated into a chitosan (Cs)-coated mesoporous silica nanocomposite (BPO@HMSNs-Cs).

Effective cancer cell killing by hydrophobic nanovoid-enhanced cavitation under safe low-energy ultrasound.

β-Cyclodextrin (β-CD)-capped mesoporous silica nanoparticles with hydrophobic internal nanovoids were prepared and used for effective cancer cell killing in synergistic combination with low-energy ultrasound (≤1.0 W cm(-2) , 1 MHz). The water-dispersible nanoparticles with hydrophobic internal nanovoids can be taken up by cancer cells and subsequently evoke a remarkable cavitation effect under irradiation with mild low-energy ultrasound (≤1.