Biomaterials, Год журнала: 2025, Номер unknown, С. 123335 - 123335
Опубликована: Апрель 1, 2025
Язык: Английский
Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)
Опубликована: Апрель 2, 2024
Abstract Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, immune cells, plays a crucial role response modulation. Nanoparticles, engineered to reshape TME, shown promising results enhancing by facilitating targeted These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, encourage T infiltration. Biomimetic further enhance increasing internalization agents cells such as cells. Moreover, exosomes, whether naturally secreted body or bioengineered, been explored regulate TME immune-related affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated pH, redox, light conditions, exhibit potential accelerate co-application with checkpoint inhibitors is an emerging strategy boost anti-tumor immunity. With their ability induce long-term immunity, nanoarchitectures are structures development. This review underscores critical overcoming current driving advancement modification.
Язык: Английский
Процитировано
131
Advanced Science, Год журнала: 2023, Номер 10(18)
Опубликована: Апрель 24, 2023
At present, radiotherapy (RT) still acquires limited success in clinical due to the lessened DNA damage under hypoxia and acquired immune tolerance owing amplified programmed death ligand-1 (PD-L1) expression. Incredibly, intracellular PD-L1 expression depression is proven better sensitize RT by inhibiting repair. However, disability of clinically used antibodies disrupting extracellular PD-L1function limits effectiveness radio-immunotherapy. Therefore, regulation strategies are urgently needed Hence, for this purpose, TPP-LND synthesized linking mitochondrial-targeted triphenylphosphine cations (TPP+ ) antineoplastic agent lonidamine (LND), which significantly reduces dose LND induce effective oxidative phosphorylation inhibition (2 vs 300 µM). Then, wrapped with liposomes form TPP-LND@Lip nanoparticles. By doing this, nanoparticles can reversing hypoxic microenvironment tumors generate more reducing via enhancing adenosine 5'-monophosphate-activated protein kinase activation. As expected, these well-designed economical than conventional anti-PD-L1 some extent.
Язык: Английский
Процитировано
48
Advanced Materials, Год журнала: 2024, Номер 36(15)
Опубликована: Янв. 17, 2024
Abstract Currently, certain cancer patients exhibit resistance to radiotherapy due reduced DNA damage under hypoxic conditions and acquired immune tolerance triggered by transforming growth factor‐β1 (TGF‐β1) membrane‐localized programmed death ligand‐1 (PD‐L1). Meanwhile, cytoplasm‐distributed PD‐L1 induces through accelerating repair (DDR). However, the disability of clinically used antibodies in inhibiting limits their effectiveness. Therefore, a nanoadjuvant is developed sensitize via multi‐level immunity activation depressing TGF‐β1 triphenylphosphine‐derived metformin, activating cGAS‐STING pathway generating Mn 2+ from MnO 2 producing more dsDNA reversing tumor hypoxia impairing DDR. Thus, Tpp‐Met@MnO @Alb effectively enhances efficiency inhibit progression irradiated local abscopal tumors lung metastases, offering long‐term memory antitumor without discernible side effects. Overall, has potential be applied for overcoming radio‐immunotherapy resistance.
Язык: Английский
Процитировано
27
Journal of Controlled Release, Год журнала: 2024, Номер 368, С. 233 - 250
Опубликована: Фев. 29, 2024
Язык: Английский
Процитировано
19
Advanced Science, Год журнала: 2024, Номер 11(26)
Опубликована: Май 7, 2024
Abstract 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 upregulation some other checkpoint inhibitors. Apart from this, such may raise occurrence rate radiation‐induced lung fibrosis (RIPF) enhanced systemic inflammation, leading ultimate cancer patients (average survival time about 3 years). Therefore, it is newly revealed that mitochondria energy metabolism regulation can be used as a novel effective PD‐L1 transforming growth factor‐β (TGF‐β) dual‐downregulation method. Following IR‐TAM prepared by conjugating mitochondria‐targeted heptamethine cyanine dye IR‐68 oxidative phosphorylation (OXPHOS) inhibitor Tamoxifen (TAM), which then self‐assembled albumin (Alb) form IR‐TAM@Alb nanoparticles. By doing tumor‐targeting nanoparticle effectively reversed tumor hypoxia depressed TGF‐β expression sensitize RT. Meanwhile, capacity targeting RIPF function TAM depressing TGF‐β, also ameliorated development induced
Язык: Английский
Процитировано
19
ACS Nano, Год журнала: 2024, Номер 18(4), С. 3331 - 3348
Опубликована: Янв. 16, 2024
Currently, limited photosensitizers possess the capacity to reverse tumor hypoxia and reduce programmed death ligand-1 (PD-L1) transforming growth factor-β (TGF-β) expression simultaneously, hindering perfect photodynamic therapy (PDT) effect due acquired immune resistance hypoxic microenvironment. To tackle these challenges, in this research, we demonstrated that mitochondrial energy metabolism depression can be utilized as an innovative efficient approach for reducing of PD-L1 TGF-β which may offer a design strategy more ideal PDT nanosystem. Through proteomic analysis 5637 cells, revealed tamoxifen (TMX) incredibly regulate cells. Then, selectively deliver clinically used depressant TMX solid tumors well nanosystem, synthesized MHI-TMX@ALB by combining mitochondria-targeted heptamethine cyanine PDT-dye MHI with through self-assembly albumin (ALB). Interestingly enough, nanoparticle effective reversion inhibition protein at lower dosage (7.5 times TMX), then enhanced efficacy immunotherapy via enhancing T-cell infiltration. Apart from this, leveraging dye's targeting toward TMX's role suppressing TGF-β, also effectively mitigated 4T1 lung metastasis development. All all, could multifunctional economical codepression immune-regulating strategy, broadening potential clinical applications
Язык: Английский
Процитировано
17
Redox Biology, Год журнала: 2024, Номер 70, С. 103073 - 103073
Опубликована: Фев. 2, 2024
Defects of human trophoblast cells may induce miscarriage (abnormal early embryo loss), which is generally regulated by lncRNAs. Ferroptosis a newly identified iron-dependent programmed cell death. Hypoxia an important and unavoidable feature in mammalian cells. However, whether hypoxia might ferroptosis then miscarriage, as well lncRNA, was completely unknown. In this work, we discovered at the first time that could result miscarriage. We also novel lncRNA (lnc-HZ06) simultaneously (indicated HIF1α protein), ferroptosis, mechanism, HIF1α-SUMO, instead itself, primarily acted transcription factor to promote NCOA4 (ferroptosis indicator) hypoxic Lnc-HZ06 promoted SUMOylation suppressing SENP1-mediated deSUMOylation. HIF1α-SUMO lnc-HZ06 transcription. Thus, both formed positive auto-regulatory feedback loop. This loop up-regulated cells, RM villous tissues, placental tissues hypoxia-treated mice, further induced up-regulating HIF1α-SUMO-mediated Furthermore, knockdown either murine lnc-hz06 or Ncoa4 efficiently suppress alleviate mouse model. Taken together, study provided new insights understanding regulatory roles lnc-HZ06/HIF1α-SUMO/NCOA4 axis among hypoxia, offered effective approach for treatment against
Язык: Английский
Процитировано
17
Advanced Science, Год журнала: 2024, Номер 11(26)
Опубликована: Май 5, 2024
Abstract It is newly revealed that collagen works as a physical barrier to tumor immune infiltration, oxygen perfusion, and depressor in solid tumors. Meanwhile, after radiotherapy (RT), the programmed death ligand‐1 (PD‐L1) overexpression transforming growth factor‐β (TGF‐β) excessive secretion would accelerate DNA damage repair trigger T cell exclusion limit RT efficacy. However, existing drugs or nanoparticles can hardly address these obstacles of highly effective simultaneously, effectively, easily. In this study, it inducing mitochondria dysfunction by using oxidative phosphorylation inhibitors like Lonidamine (LND) serve multi‐immune pathway regulation strategy through PD‐L1, collagen, TGF‐β co‐depression. Then, IR‐LND prepared combining mitochondria‐targeted molecule IR‐68 with LND, which then loaded liposomes (Lip) create IR‐LND@Lip nanoadjuvants. By doing this, more effectively sensitizes generating cold tumors into hot ones activation co‐inhibition. conclusion, combined treatment ultimately almost completely suppressed bladder breast
Язык: Английский
Процитировано
17
Bioactive Materials, Год журнала: 2024, Номер 39, С. 206 - 223
Опубликована: Май 21, 2024
Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, minimal adverse effects. The combination of photodynamic therapy (PDT) immunotherapy gradually become a promising approach high-grade malignant NSCLC. Nevertheless, owing the absence precise drug delivery techniques as well hypoxic immunosuppressive characteristics tumor microenvironment (TME), efficacy less than ideal. In study, we construct novel nanoplatform indocyanine green (ICG), photosensitizer, loads into hollow manganese dioxide (MnO
Язык: Английский
Процитировано
16
International Journal of Biological Macromolecules, Год журнала: 2023, Номер 254, С. 127911 - 127911
Опубликована: Ноя. 7, 2023
Язык: Английский
Процитировано
25