Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 100, P. 105995 - 105995
Published: July 30, 2024
Language: Английский
Advanced Materials, Journal Year: 2024, Volume and Issue: 36(15)
Published: Jan. 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.
Language: Английский
Citations
31
Advanced Science, Journal Year: 2024, Volume and Issue: 11(26)
Published: May 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
Language: Английский
Citations
18
Medical Oncology, Journal Year: 2025, Volume and Issue: 42(2)
Published: Jan. 9, 2025
Language: Английский
Citations
3
Journal of Drug Delivery Science and Technology, Journal Year: 2025, Volume and Issue: unknown, P. 106847 - 106847
Published: March 1, 2025
Language: Английский
Citations
3
Biomaterials, Journal Year: 2025, Volume and Issue: 317, P. 123094 - 123094
Published: Jan. 7, 2025
Language: Английский
Citations
2
ACS Nano, Journal Year: 2024, Volume and Issue: 18(4), P. 3331 - 3348
Published: Jan. 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
Language: Английский
Citations
17
European Journal of Pharmaceutics and Biopharmaceutics, Journal Year: 2024, Volume and Issue: 200, P. 114323 - 114323
Published: May 15, 2024
Language: Английский
Citations
12
Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(9), P. 4087 - 4101
Published: June 3, 2024
Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to impaired PTX@Alb accumulation in tumors partly mediated by dense collagen distribution. Meanwhile, acquired immune resistance always occurs enhanced programmed cell death-ligand 1 (PD-L1) expression after treatment, which then leads tolerance. To fill these gaps, we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer with mitochondrial metabolism blockade capacity, could also be as novel effective PD-L1 and TGF-
Language: Английский
Citations
12
Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 560 - 560
Published: Jan. 28, 2024
Gastric carcinoma, being one of the most prevalent types solid tumors, has emerged as third leading cause death worldwide. The symptoms gastric cancer (GC) are typically complex, which makes early detection challenging. Immune checkpoint inhibition become new standard targeted therapy for advanced or metastatic GC. It is currently explored in various combinations, both with and without chemotherapy, across multiple therapies clinical trials. Immunotherapy can stimulate immune responses GC patients, to destruction cells. Compared traditional therapies, immunotherapy shown strong effectiveness tolerable toxicity levels. Hence, this innovative approach treatment gained popularity. In review, we have outlined recent advancements GC, including inhibitors, vaccines, vascular endothelial growth factor-A chimeric antigen receptor T-cell therapy. Our current emphasis on examining immunotherapies presently employed settings, addressing existing challenges associated these therapeutic approaches, exploring promising strategies overcome their limitations.
Language: Английский
Citations
11
Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1924 - 1924
Published: Nov. 20, 2024
Identifying definitive biomarkers that predict clinical response and resistance to immunotherapy remains a critical challenge. One emerging factor is extracellular acidosis in the tumor microenvironment (TME), which significantly impairs immune cell function contributes failure. However, acidic conditions TME disrupt interaction between cancer cells, driving tumor-infiltrating T cells NK into an inactivated, anergic state. Simultaneously, promotes recruitment activation of immunosuppressive such as myeloid-derived suppressor regulatory (Tregs). Notably, acidity enhances exosome release from Tregs, further amplifying immunosuppression. Tumor thus acts "protective shield," neutralizing anti-tumor responses transforming pro-tumor allies. Therefore, targeting lactate metabolism has emerged promising strategy overcome this barrier, with approaches including buffer agents neutralize pH inhibitors block production or transport, thereby restoring efficacy TME. Recent discoveries have identified genes involved (pHe) regulation, presenting new therapeutic targets. Moreover, ongoing research aims elucidate molecular mechanisms acidification develop treatments modulate levels enhance outcomes. Additionally, future studies are crucial validate safety pHe-targeted therapies patients. Thus, review explores regulation pHe its potential role improving immunotherapy.
Language: Английский
Citations
8