Mitochondria Energy Metabolism Depression as Novel Adjuvant to Sensitize Radiotherapy and Inhibit Radiation Induced-Pulmonary Fibrosis.

Currently, the typical combination therapy of programmed death ligand-1 (PD-L1) antibodies with radiotherapy (RT) still exhibits impaired immunogenic antitumor response in clinical due to lessened DNA damage and acquired immune tolerance via the upregulation of some other immune checkpoint inhibitors. Apart from this, such combination therapy may raise the occurrence rate of radiation-induced lung fibrosis (RIPF) due to enhanced systemic inflammation, leading to the ultimate death of cancer patients (average survival time of about 3 years). Therefore, it is newly revealed that mitochondria energy metabolism regulation can be used as a novel effective PD-L1 and transforming growth factor-β (TGF-β) dual-downregulation method.

Mitochondria-Targeted Nanoadjuvants Induced Multi-Functional Immune-Microenvironment Remodeling to Sensitize Tumor Radio-Immunotherapy.

It is newly revealed that collagen works as a physical barrier to tumor immune infiltration, oxygen perfusion, and immune depressor in solid tumors. Meanwhile, after radiotherapy (RT), the programmed death ligand-1 (PD-L1) overexpression and transforming growth factor-β (TGF-β) excessive secretion would accelerate DNA damage repair and trigger T cell exclusion to limit RT efficacy. However, existing drugs or nanoparticles can hardly address these obstacles of highly effective RT simultaneously, effectively, and easily.

Erratum: Author correction to "Cascade two-stage tumor re-oxygenation and immune re-sensitization mediated by self-assembled albumin-sorafenib nanoparticles for enhanced photodynamic immunotherapy" [Acta Pharm Sin B (2022) 4204-4223].

[This corrects the article DOI: 10.1016/j.apsb.

A Hybrid Nanoadjuvant Simultaneously Depresses PD-L1/TGF-β1 and Activates cGAS-STING Pathway to Overcome Radio-Immunotherapy Resistance.

Currently, certain cancer patients exhibit resistance to radiotherapy due to reduced DNA damage under hypoxic conditions and acquired immune tolerance triggered by transforming growth factor-β1 (TGF-β1) and membrane-localized programmed death ligand-1 (PD-L1). Meanwhile, cytoplasm-distributed PD-L1 induces radiotherapy resistance through accelerating DNA damage repair (DDR). However, the disability of clinically used PD-L1 antibodies in inhibiting cytoplasm-distributed PD-L1 limits their effectiveness.

Metabolic Intervention Liposome Boosted Lung Cancer Radio-Immunotherapy via Hypoxia Amelioration and PD-L1 Restraint.

At present, radiotherapy (RT) still acquires limited success in clinical due to the lessened DNA damage under hypoxia and acquired immune tolerance owing to the amplified programmed death ligand-1 (PD-L1) expression. Incredibly, intracellular PD-L1 expression depression is proven to better sensitize RT by inhibiting DNA damage repair. However, the disability of the clinically used antibodies in disrupting the extracellular PD-L1function still limits the effectiveness of radio-immunotherapy.

Cascade two-stage tumor re-oxygenation and immune re-sensitization mediated by self-assembled albumin-sorafenib nanoparticles for enhanced photodynamic immunotherapy.

As a promising modality for cancer therapy, photodynamic therapy (PDT) still acquired limited success in clinical nowadays due to the extremely serious hypoxia and immunosuppression tumor microenvironment. To ameliorate such a situation, we rationally designed and prepared cascade two-stage re-oxygenation and immune re-sensitization BSA-MHI148@SRF nanoparticles hydrophilic and hydrophobic self-assembly strategy by using near-infrared photodynamic dye MHI148 chemically modified bovine serum albumin (BSA-MHI148) and multi-kinase inhibitor Sorafenib (SRF) as a novel tumor oxygen and immune microenvironment regulation drug. Benefiting from the accumulation of SRF in tumors, BSA-MHI148@SRF nanoparticles dramatically enhanced the PDT efficacy by promoting cascade two-stage tumor re-oxygenation mechanisms: (i) SRF decreased tumor oxygen consumption inhibiting mitochondria respiratory.

Metabolic reprogramming mediated PD-L1 depression and hypoxia reversion to reactivate tumor therapy.

As a promising cancer treatment, photodynamic therapy (PDT) still achieved limited clinical success due to the severe hypoxia and programmed death ligand-1 (PD-L1) over-expressed immunosuppression tumor microenvironment. At present, few methods have been proven to solve these two defects simply and effectively by a single drug or nano-system simultaneously. To ameliorate this situation, we designed and constructed MB@Bu@MnO nanoparticles with two-step oxygen regulation ability and PD-1/PD-L1 axis cascade-disruption capacity via a biomineralization method.

Metformin modified chitosan as a multi-functional adjuvant to enhance cisplatin-based tumor chemotherapy efficacy.

Recently, it was newly revealed that the DNA damage induced by cis‑platinum (Cis-Pt) mediated chemotherapy was significantly impaired by the highly expressed programmed death ligand-1 (PD-L1) in tumor cells. Besides, the efficacy of Cis-Pt was also limited due to its severe side effects, especially enhanced drug efflux induced by multidrug resistance protein 1 (MDR-1) and increased tumor metastasis. Up to now, few drugs or carbohydrates could simultaneously solve these defects of Cis-Pt mediated chemotherapy.

Tumor Selective Metabolic Reprogramming as a Prospective PD-L1 Depression Strategy to Reactivate Immunotherapy.

Currently, the role of the lysosome, endoplasmic reticulum, or dictyosome in the transcription and translation of programmed cell death ligand 1 (PD-L1) is well revealed, but the role and function of mitochondria in the PD-L1 expression in tumors is still not fully researched, making it hard to offer a novel PD-L1 regulation strategy. In this research, it is newly revealed that mitochondria oxidative phosphorylation (OXPHOS) depression can be used as an effective PD-L1 down-regulation method. To offer an ideal and high-effective tumor mitochondria-targeted OXPHOS depression nanosystem, IR-LND is prepared by conjugating mitochondria-targeted heptamethine cyanine dye IR-68 with mitochondrial complexes I and II depression agent lonidamine (LND), which then further self-assembled with albumin (Alb) to form IR-LND@Alb nanoparticles.

Chitosan biguanide induced mitochondrial inhibition to amplify the efficacy of oxygen-sensitive tumor therapies.

At present, the tumor's poor oxygen perfusion and limited tumor drug permeation are the major bottlenecks that limit the therapeutic effectiveness of the oxygen-sensitive antitumor therapies, like doxorubicin (Dox)-mediated chemotherapy and photodynamic therapy (PDT). To our best knowledge, the abnormal tumor mitochondria oxidative phosphorylation (OXPHOS) was the vital cause of such phenomenon, which induced the hypoxia tumor microenvironment and enhanced drug efflux from tumor cells via enhanced multidrug resistance protein 1 (MDR-1) expression. In this study, it was newly revealed that biguanide-modified chitosan (Bi-Ch) possessed ideal mitochondria depression capacity, leading to the following decreased dosage needed to disrupt mitochondrial function to reverse tumor hypoxia and depress MDR-1 expression.

Chitosan oligosaccharide regulates AMPK and STAT1 pathways synergistically to mediate PD-L1 expression for cancer chemoimmunotherapy.

After regular chemotherapy, the expression of programmed cell death ligand 1 (PD-L1) in almost all kinds of cancers is significantly increased, leading to reduced efficacy of T cell mediated immune killing in tumors. To solve this, a lot of PD-L1 antibodies were produced and used, but their high cost and serious toxic side effects still limit its usage. Recently, small molecule compounds that could effectively regulate PD-L1 expression possess the edges to solve the problems of PD-L1 antibodies.

Selectively down-regulated PD-L1 by albumin-phenformin nanoparticles mediated mitochondrial dysfunction to stimulate tumor-specific immunological response for enhanced mild-temperature photothermal efficacy.

Background: Mild-temperature photothermal therapy (mild-PTT) has emerged as a highly promising antitumor strategy by triggering immunogenic cell death (ICD) to elicit both innate and adaptive immune responses for tumor control. However, mild-PTT still leads to the risk of tumor recurrence or metastasis because it could hardly completely eradicate tumors due to its impaired immunological efficacy owing to the enhanced PD-L1 expression in tumor cells after treatment.

Results: In this study, we described a hydrogen peroxide (HO) responsive manganese dioxide mineralized albumin nanocomposite loading with mitochondria function inhibitor phenformin (PM) and near-infrared photothermal dye indocyanine green (ICG) by modified two-step biomineralization method.

Effective tumor vessel barrier disruption mediated by perfluoro-N-(4-methylcyclohexyl) piperidine nanoparticles to enhance the efficacy of photodynamic therapy.

Currently, limited tumor drug permeation, poor oxygen perfusion and immunosuppressive microenvironments are the most important bottlenecks that significantly reduce the efficacy of photodynamic therapy (PDT). The main cause of these major bottlenecks is the platelet activation maintained abnormal tumor vessel barriers. Thus, platelet inhibition may present a new way to most effectively enhance the efficacy of PDT.

Metformin Liposome-Mediated PD-L1 Downregulation for Amplifying the Photodynamic Immunotherapy Efficacy.

Photodynamic therapy (PDT) is a promising strategy for cancer treatment. It can not only generate reactive oxygen species (ROS) to cause the chemical damage of tumor cells in the presence of enough oxygen but also promote the antitumor immunity of T cells through enhancing the production of interferon γ (IFN-γ). However, one phenomenon is ignored so far that the enhanced production of IFN-γ caused by PDT may significantly increase the expression of programmed death-ligand 1 (PD-L1) on the tumor cell membrane and thus could inhibit the immune killing effects of T cells.

Erratum: Two-stage oxygen delivery for enhanced radiotherapy by perfluorocarbon nanoparticles: Erratum.

[This corrects the article DOI: 10.7150/thno.27598.

Biocompatible Hydrogels Based on Food Gums with Tunable Physicochemical Properties as Scaffolds for Cell Culture.

Hydrogels composed of food gums have gained attention for future biomedical applications, such as targeted delivery and tissue engineering. For their translation to clinical utilization, reliable biocompatibility, sufficient mechanical performance, and tunable structure of polysaccharide hydrogels are required aspects. In this work, we report a unique hybrid polysaccharide hydrogel composed of salecan and curdlan, in which the former is a thickening agent and the latter serves as a network matrix.

Macroporous Hydrogel Scaffolds with Tunable Physicochemical Properties for Tissue Engineering Constructed Using Renewable Polysaccharides.

Polysaccharides have recently attracted increasing attention in the construction of hydrogel devices for biomedical applications. However, polysaccharide-based hydrogels are not suitable for most preclinical applications because of their limited mechanical properties and poor tunability. In this study, we employed a simple and eco-friendly approach to producing a macroporous polysaccharide hydrogel composed of salecan and κ-carrageenan without the use of toxic chemicals.

Directed arrangement of siRNA via polymerization-induced electrostatic self-assembly.

Herein, polymerization-induced electrostatic self-assembly (PIESA) is conducted to mediate the self-assembly behavior of short interfering RNA (siRNA) for the first time. In PIESA, siRNA not only formed a simple electrostatic polyplex with positively charged polycations, but also facilitated directed self-assembly due to the molecular rigidity of siRNA, leading to appealing nanotubes.

Facile formation of salecan/agarose hydrogels with tunable structural properties for cell culture.

Salecan polysaccharide produced by Agrobacterium sp. ZX09 is an attractive biopolymer to construct hydrogel scaffolds for cell culture. However, some limitations such as poor mechanical performance, complicated fabrication process and slow gelation times still exist in the biomedical applications of microbial-based salecan polysaccharide hydrogels.

Perfluorocarbon nanoparticle-mediated platelet inhibition promotes intratumoral infiltration of T cells and boosts immunotherapy.

Cancer immunotherapy can stimulate and enhance the ability of the immune system to recognize, arrest, and eliminate tumor cells. Immune checkpoint therapies (e.g.

Two-stage oxygen delivery for enhanced radiotherapy by perfluorocarbon nanoparticles.

Tumors are usually hypoxic, which limits the efficacy of current tumor therapies, especially radiotherapy in which oxygen is essential to promote radiation-induced cell damage. Herein, by taking advantage of the ability of perfluorocarbon (PFC) to promote red blood cell penetration, we developed a simple but effective two-stage oxygen delivery strategy to modulate the hypoxic tumor microenvironment using PFC nanoparticles. We first examined the two-stage oxygen delivery ability of PFC nanoparticles on relieving tumor hypoxia through platelet inhibition.

Perfluorocarbon Nanoparticles Mediated Platelet Blocking Disrupt Vascular Barriers to Improve the Efficacy of Oxygen-Sensitive Antitumor Drugs.

Currently, limited tumor drug permeation and poor oxygen perfusion are two major bottlenecks that significantly impair the efficacy of existing antitumor drugs, especially oxygen-sensitive antitumor drugs. One vital cause of these major bottlenecks is the abnormal tumor vessel barrier. To the best knowledge of the authors, platelets play a vital role in the maintenance of an abnormal tumor blood barrier through platelet-tumor interaction.