AIEgen-self-assembled nanoparticles with anti-PD-L1 antibody functionalization realize enhanced synergistic photodynamic therapy and immunotherapy against malignant melanoma DOI Creative Commons
Li Lü, Qing Xu, Xiuzhen Zhang

et al.

Materials Today Bio, Journal Year: 2024, Volume and Issue: 30, P. 101387 - 101387

Published: Dec. 6, 2024

Immune checkpoint inhibitors (ICIs) become integral in clinical practice, yet their application cancer therapy is constrained by low overall response rates and the primary resistance of cancers to ICIs. Herein, this study proposes aggregation-induced emission (AIE)-based nanoparticles (NPs) for a more effective synergistic approach combining immunotherapy photodynamic (PDT) achieve higher responses than anti-PD-L1 monotherapy. The TBP@aPD-L1 NPs are constructed functionalizing azide group-modified TBP-2 (TBP-N3) with antibodies via DBCO-S-S-PEG2000-COOH linker. target tumor cells promote TBP-N3 accumulation tumors enhanced PDT. Notably, TBP-N3, featuring emission, boosts reactive oxygen species (ROS) generation through both type I II processes TBP@aPD-L1-mediated PDT induces powerful effects direct cell-killing further elicits immunogenic cell death (ICD), which exerts anti-tumor immunity activating T ICI treatment reshapes immune microenvironment (TIME), thereby enhancing efficacy PD-L1 blockade anti-PD-L1. Consequently, demonstrated significantly inhibition growth mouse model malignant melanoma (MM). Our act as facile drug delivery platform combined treating MM.

Language: Английский

A Hybrid Nanoadjuvant Simultaneously Depresses PD‐L1/TGF‐β1 and Activates cGAS‐STING Pathway to Overcome Radio‐Immunotherapy Resistance DOI
Yi Lei, Xin Jiang, Zaigang Zhou

et al.

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

30
Mitochondrial Disruption Nanosystem Simultaneously Depressed Programmed Death Ligand-1 and Transforming Growth Factor-β to Overcome Photodynamic Immunotherapy Resistance DOI
Xin Jiang, Yi Lei, Cheng Li

et al.

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
Mitochondria‐Targeted Nanoadjuvants Induced Multi‐Functional Immune‐Microenvironment Remodeling to Sensitize Tumor Radio‐Immunotherapy DOI Creative Commons
Zaigang Zhou, Cheng Li, Chao Li

et al.

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

17
Platinum nanoparticles in cancer therapy: chemotherapeutic enhancement and ROS generation DOI

Emmanuel Faderin,

Terungwa H. Iorkula,

Omowunmi Rebecca Aworinde

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(2)

Published: Jan. 9, 2025

Language: Английский

Citations

3
Liposomes as Immunotherapeutic Carriers: A Game-Changer in Cancer Therapy DOI

Sepehr Hoseinzadeh Moghaddam,

Abulfazl Vatankhah,

Fatemeh Oroojalian

et al.

Journal of Drug Delivery Science and Technology, Journal Year: 2025, Volume and Issue: unknown, P. 106847 - 106847

Published: March 1, 2025

Language: Английский

Citations

2
Therapeutic Immunomodulation in Gastric Cancer DOI Open Access
Akkanapally Venu, Xue‐Feng Bai, Sujit Basu

et al.

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
Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy DOI Creative Commons
Zaigang Zhou,

Wenjuan Luo,

Chunjuan Zheng

et al.

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

11
Enhancing cancer immunotherapy: Exploring strategies to target the PD-1/PD-L1 axis and analyzing the associated patent, regulatory, and clinical trial landscape DOI

S. S. Kirthiga Devi,

S. D. Singh, Ramesh Joga

et al.

European Journal of Pharmaceutics and Biopharmaceutics, Journal Year: 2024, Volume and Issue: 200, P. 114323 - 114323

Published: May 15, 2024

Language: Английский

Citations

10
Emerging Role of Extracellular pH in Tumor Microenvironment as a Therapeutic Target for Cancer Immunotherapy DOI Creative Commons
Md. Ataur Rahman,

Mahesh Kumar Yadab,

Meser M. Ali

et al.

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
Transarterial Radioembolization (TARE) in Patients with Hepatocellular Carcinoma: A Comparison of Palliative with Bridging-to-Transplant Concepts DOI Open Access

Jacqueline Schönherr,

Philipp Seifert,

Falk Gühne

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(1), P. 235 - 235

Published: Jan. 4, 2024

We investigated transarterial radioembolization (TARE) as a palliative measure and bridging-to-transplant therapy in hepatocellular carcinoma (HCC) patients. A total of 167 patients (50 bridging, 117 palliative) with 245 TARE procedures were assessed. Fourteen underwent subsequent liver transplantation (LT). Patients undergoing LT exhibited significantly prolonged progression-free survival (PFS) compared to those bridging-without-transplant (p = 0.033). No significant differences observed between cases 0.116). Median overall (OS) post-TARE was 16.6 months, estimated OS rates at 6/12 months 82.0%/60.5%, respectively. who demonstrated statistically longer 0.001). marked outcome distinctions found groups. The findings underscored the superiority over alternative treatments. served an important component non-LT scenarios, allowing for therapeutic options. study reflected highly variable complex situations HCC, emphasizing need further investigations define optimal multimodal approach.

Language: Английский

Citations

5