Targeting Senescent Alveolar Type 2 Cells with a Gene-Editable FePt Dual-Atom Catalyst for Mitigating Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) remains an age-related, fatal, incurable, epithelial-driven fibrotic lung disease despite the availability of approved antifibrotic drugs. The medical need for effective antipulmonary fibrotic therapies is thus very high. A promising therapeutic intervention for IPF is to target key cellular senescence processes in alveolar type 2 (AT2) cells.

Reactive oxygen species responsive nanomotors for gene edited metabolic disruption and immunotherapy.

While gene-editing-based tumor therapy holds promise, conventional passive-diffusion vectors face limited penetration in dense solid tumors. Here, we developed a ROS-driven gene editing nanomotor (RDN@PL), which takes hemin as the core and encapsulates CRISPR/Cas9 plasmids targeting LDHA (A glycolysis key enzyme). In tumor microenvironments, RDN@PL consumes extracellular ROS to fuel self-diffusiophoresis, achieving higher intratumoral accumulation than passive particles.

Polyamine-Depleting Hydrogen-Bond Organic Frameworks Unleash Dendritic Cell and T Cell Vigor for Targeted CRISPR/Cas-Assisted Cancer Immunotherapy.

Polyamines have tantalized cancer researchers as a potential means to rein in the rampant growth of cancer cells. However, clinical trials in recent decades have disappointed in delivering notable progress. Herein, a microfluidic-assisted synthetic hydrogen-bond organic framework (HOF) as a polyamine-depleting nanoplatforms designed to unleash the vigor of both dendritic cells (DCs) and T cells for precision cancer immunotherapy is reported.

Self-Metallized Whole Cell Vaccines Prepared by Microfluidics for Bioorthogonally Catalyzed Antitumor Immunotherapy.

Tumor whole cell, carrying a complete set of tumor-associated antigens and tumor-specific antigens, has shown great potential in the construction of tumor vaccines but is hindered by the complex engineering means and limited efficacy to cause immunity. Herein, we provided a strategy for the self-mineralization of autologous tumor cells with palladium ions in microfluidic droplets, which endowed the engineered cells with both immune and catalytic functions, to establish a bioorthogonally catalytic tumor whole-cell vaccine. This vaccine showed strong inhibition both in the occurrence and recurrence of tumor by invoking the immediate antitumor immunity and building a long-term immunity.

Self-Generating Gold Nanocatalysts in Autologous Tumor Cells for Targeted Catalytic Immunotherapy.

Employing tumor whole cells for tumor immunotherapy is a promising tumor therapy proposed in the early stage, but its therapeutic efficacy is weakened by the methods of eliminating pathogenicity and the mass ratio of the effective antigen carried by itself. Here, by adding gold ion to live cancer cells in the microfluidic droplets, this work obtains dead tumor whole cells with NIR-controlled catalytic ability whose pathogenicity is removed while plenary tumor antigens, major structure, and homing ability are reserved. The engineered tumor cell (Cell-Au) with the addition of prodrug provides O in an O-free Russell mechanism, which serves better in a hypoxic tumor microenvironment.

Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy.

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/HO-mediated/starvation multimodal cancer therapy.

Activation of the cGAS-STING pathway combined with CRISPR-Cas9 gene editing triggering long-term immunotherapy.

Effective activation of cGAS-STING pathway combined with immune checkpoint blockade (ICB) within the immunosuppressive tumor microenvironment to induce stronger immune responsiveness yet remains challenging. CRISPR-Cas9 gene editing technology, which offers the benefits of permanence and irreversibility, could recognize the target genome sequence with sgRNA (Guide RNA) and guide the Cas9 protease to knock down the target gene. Herein, a nanoplatform (HMnMPH) for dual activation of cGAS-STING pathway in combination with CRISPR-Cas9 gene editing to silence programmed death ligand 1 (PD-L1) to trigger long-term immunotherapy was reported.

DNAzyme-Assisted Nano-Herb Delivery System for Multiple Tumor Immune Activation.

As a promising therapeutic strategy against cancer, immunotherapy faces critical challenges, especially in solid tumors. Immune checkpoint blockade therapy, particularly blocking the interaction of the programmed cell death 1 (PD1)-PD1 ligand 1 (PD-L1) axis, can reverse the suppression of T cells so as to destroy tumor cells and exert antitumor effects. Here, a strategy of multiple activation of immune pathways is developed, to provide supporting evidence for potential antitumor therapies.

Synergistic Lysosomal Impairment and ER Stress Activation for Boosted Autophagy Dysfunction Based on Te Double-Headed Nano-Bullets.

To overcome the autophagy compromised mechanism of protective cellular processes by "eating"/"digesting" damaged organelles or potentially toxic materials with autolysosomes in tumor cells, lysosomal impairment can be utilized as a traditional autophagy dysfunction route for tumor therapy; however, this conventional one-way autophagy dysfunction approach is always limited by the therapeutic efficacy. Herein, an innovative pharmacological strategy that can excessively provoke autophagy via endoplasmic reticulum (ER) stress is implemented along with lysosomal impairment to enhance autophagy dysfunction. In this work, the prepared tellurium double-headed nanobullets (TeDNBs) with controllable morphology are modified with human serum albumin (HSA) which facilitates internalization by tumor cells.

SO prodrug doped nanorattles with extra-high drug payload for "collusion inside and outside" photothermal/pH triggered - gas therapy.

Recent years have witnessed the blooming of gas therapy nanoplatforms, which emerged as a promising area for cancer therapy. However, uncontrolled or inadequate generation of gas and unclear therapeutic mechanisms, which were still regarded as big challenges to apply gas therapy into clinical. Here in, a gas treatment based on sulfur dioxide (SO) prodrug doped nanorattles was explored, which could not only inhibit superficial tumor but also deep tumor.

Boosted photocatalytic activity induced NAMPT-Regulating therapy based on elemental bismuth-humic acids heterojunction for inhibiting tumor proliferation/migration/inflammation.

Due to the highly complex biological formation procedure, tumor is still difficult to be treated efficiently and always associated with proliferation, migration and inflammation during treatment. Herein, a novel strategy of boosted photocatalytic activity induced NAMPT-regulating therapy is used for tumors inhibition based on FK866 loaded bismuth-humic acids heterojunction (Bi-HA/FK866). With the reduction function of HA, Bi (Ⅲ) can be reduced to elemental Bi, which can be excited by NIR laser to form electron-hole pair due to the narrow bandgap.

Enhanced Bax upregulating in mitochondria for deep tumor therapy based on SO prodrug loaded Au-Ag hollow nanotriangles.

Nowadays, limited deep tumor penetration and lower therapeutic effect are still the major obstacle in nanomedicines for cancer therapy. Here, we developed high-efficiency nanocomposites, SO prodrug (BTS) loaded Au-Ag hollow nanotriangles (Au-Ag-BTS HTNs), which could not only synergistically upregulate Bax expression in mitochondria, but also be triggered by acidic tumor microenvironment to generate SO for deep tumor therapy. Upon NIR laser irradiation, Au-Ag hollow nanotriangles (Au-Ag HTNs) produced plenty of heat for photothermal therapy (PTT), while the acidic condition in tumor cells induced on-demand SO release from BTS for deep tumor therapy.

Photothermally activatable PDA immune nanomedicine combined with PD-L1 checkpoint blockade for antimetastatic cancer photoimmunotherapy.

Photothermal therapy (PTT) has shown promising potential and bright prospects in damaging primary tumors; however, it is limited to metastatic and recrudescent tumors as PTT requires straightforward light irradiation. Moreover, metastatic and recrudescent tumor immunosuppression due to host T-cell antitumor activity is dramatically impeded because of programmed cell death 1 ligand (PD-L1) and programmed cell death receptor 1 (PD-1) pathways and immune checkpoint blockade (ICB) therapy. In this work, we demonstrate that PTT combined with ICB could not only eliminate primary tumors, but also prevent tumor metastasis to the lungs/liver.

Ultra-small BiS nanodot-doped reversible Fe(ii/iii)-based hollow mesoporous Prussian blue nanocubes for amplified tumor oxidative stress-augmented photo-/radiotherapy.

Improving the generation of reactive oxygen species (ROS) while consuming glutathione (GSH) is the main method for amplifying intracellular oxidative stress. However, in previous studies, it was normally necessary to combine two or more materials to achieve the effect of destroying the intracellular redox homeostasis. This made the preparation process relatively complicated.

Rod-shape MSN@MoS Nanoplatform for FL/MSOT/CT Imaging-Guided Photothermal and Photodynamic Therapy.

Rod-shape nanoplatform have received tremendous attention owing to their enhanced ability for cell internalization and high capacity for drug loading. MoS, widely used in electronic devices, electrocatalysis, sensor and energy-storage, has been studied as photothermal agents over the years. However, the efficacy of rod-shape MoS based photothermal agents for photothermal therapy has not been studied before.

Glutathione-Mediated Clearable Nanoparticles Based on Ultrasmall GdO for MSOT/CT/MR Imaging Guided Photothermal/Radio Combination Cancer Therapy.

Recently, multifunctional clearable inorganic theranostic nanoparticles have been attracting more and more attention. Protein-based nanoparticles can be cleared by the hepatobiliary system efficiently. In this work, ultrasmall gadolinium oxide (GdO) nanoparticles, which possess the advantage of high longitudinal relaxation rate, were coated with bovine serum albumin (BSA).

MSOT/CT/MR imaging-guided and hypoxia-maneuvered oxygen self-supply radiotherapy based on one-pot MnO-mSiO@Au nanoparticles.

Radiotherapy (RT) is one of the most widely applied treatments for cancer therapy in clinics. Herein, we constructed innovative multifunctional nanotheranostic MnO2-mSiO2@Au-HA nanoparticles (MAHNPs) based on one-pot MnO2-mSiO2 nanohybrids (MNHs) and gold nanoparticles (AuNPs) for multispectral optoacoustic tomography (MSOT)/computed tomography (CT) and magnetic resonance (MR) imaging-guided hypoxia-maneuvered radiotherapy. The MNHs were prepared via a facile one-pot approach, which avoided the leakage of MnO2 nanoparticles and increased the synthetic efficiency.

Rodlike MSN@Au Nanohybrid-Modified Supermolecular Photosensitizer for NIRF/MSOT/CT/MR Quadmodal Imaging-Guided Photothermal/Photodynamic Cancer Therapy.

Recently, rodlike nanomaterials with specific aspect ratio for efficient cellular uptake have received enormous attention. For functional nanomaterials, such as photothermal agents, large surface areas for their rod-shaped exterior that increase the amount of light absorbed would lead to a higher absorption coefficient as well as drug-loading property. In this project, we coated rodlike mesoporous silica with gold nanoshells (MSNR@Au hybrid), modifying them with ultrasmall gadolinium (Gd)-chelated supramolecular photosensitizers, TPPS (MSNR@Au-TPPS(Gd)), which could be applied to near-infrared fluorescence/multispectral optoacoustic tomography/computed tomography/magnetic resonance imaging and imaging-guided remotely controlled photothermal (PTT)/photodynamic (PDT) combined antitumor therapy.

Ultrasmall MoS Nanodots-Doped Biodegradable SiO Nanoparticles for Clearable FL/CT/MSOT Imaging-Guided PTT/PDT Combination Tumor Therapy.

Recently, we developed ultrasmall molybdenum disulfide (MoS) quantum dots for computed tomography (CT) and multispectral optoacoustic tomography (MSOT) imaging-guided photothermal therapy (PTT). But, due to rapid body elimination and limited blood circulation time, the tumor uptake of the dots is low. In our study, this problem was solved via designing an amino-modified biodegradable nanomaterial based on MoS quantum-dots-doped disulfide-based SiO nanoparticles (denoted MoS@ss-SiO) for multimodal application.