PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 1, 2021

Programmed death protein 1 (PD1) is a common immunosuppressive member on the surface of T cells and plays an imperative part in downregulating immune system advancing self-tolerance. Its ligand programmed cell (PDL1) overexpressed malignant tumor cells, where it binds to PD1, inhibits proliferation PD1-positive participates evasion tumors leading treatment failure. The PD1/PDL1-based pathway great value immunotherapy cancer has become important checkpoint recent years, so understanding mechanism PD1/PDL1 action significance for combined patient prognosis. inhibitors have shown clinical efficacy many tumors, example, blockade PD1 or PDL1 with specific antibodies enhances responses mediates antitumor activity. However, some patients are prone develop drug resistance, resulting poor outcomes, which rooted insensitivity targeted inhibitors. In this paper, we reviewed application immunotherapy. We hope that future, promising combination therapy regimens can be developed allow immunotherapeutic tools play role treatment. also discuss safety issues further reflect effectiveness side effects brings.

Language: Английский

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Nanomedicine in cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 7, 2023

Cancer remains a highly lethal disease in the world. Currently, either conventional cancer therapies or modern immunotherapies are non-tumor-targeted therapeutic approaches that cannot accurately distinguish malignant cells from healthy ones, giving rise to multiple undesired side effects. Recent advances nanotechnology, accompanied by our growing understanding of biology and nano-bio interactions, have led development series nanocarriers, which aim improve efficacy while reducing off-target toxicity encapsulated anticancer agents through tumor tissue-, cell-, organelle-specific targeting. However, vast majority nanocarriers do not possess hierarchical targeting capability, their indices often compromised poor accumulation, inefficient cellular internalization, inaccurate subcellular localization. This Review outlines current prospective strategies design organelle-targeted nanomedicines, highlights latest progress technologies can dynamically integrate these three different stages static maximize outcomes. Finally, we briefly discuss challenges future opportunities for clinical translation nanomedicines.

Language: Английский

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Recent advances in targeted antibacterial therapy basing on nanomaterials

Exploration, Journal Year: 2023, Volume and Issue: 3(1)

Published: Feb. 1, 2023

Bacterial infection has become one of the leading causes death worldwide, particularly in low-income countries. Despite fact that antibiotics have provided successful management bacterial infections, long-term overconsumption and abuse contributed to emergence multidrug resistant bacteria. To address this challenge, nanomaterials with intrinsic antibacterial properties or serve as drug carriers been substantially developed an alternative fight against infection. Systematically deeply understanding mechanisms is extremely important for designing new therapeutics. Recently, nanomaterials-mediated targeted bacteria depletion either a passive active manner most promising approaches treatment by increasing local concentration around cells enhance inhibitory activity reduce side effects. Passive targeting approach widely explored searching nanomaterial-based alternatives antibiotics, while strategy relies on biomimetic biomolecular surface feature can selectively recognize In review article, we summarize recent developments field therapy based nanomaterials, which will promote more innovative thinking focusing multidrug-resistant

Language: Английский

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Aptamer-assisted tumor localization of bacteria for enhanced biotherapy

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Nov. 15, 2021

Despite bacterial-mediated biotherapies have been widely explored for treating different types of cancer, their implementation has restricted by low treatment efficacy, due largely to the absence tumor-specific accumulation following administration. Here, conjugation aptamers bacterial surface is described a simple and cytocompatible amidation procedure, which can significantly promote localization bacteria in tumor site after systemic The density be easily adjusted varying feed ratio able increase stability anchored aptamers. Optimal conjugated with an average 2.8 × 10

Language: Английский

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Regulatory mechanisms of PD-1/PD-L1 in cancers

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 18, 2024

Abstract Immune evasion contributes to cancer growth and progression. Cancer cells have the ability activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) cell ligands (PD-Ls) are considered be major molecules. interaction of PD-1 PD-L1 negatively regulates adaptive response mainly by inhibiting activity effector T while enhancing function regulatory (Tregs), largely contributing maintenance homeostasis prevents dysregulated immunity harmful responses. However, exploit PD-1/PD-L1 axis cause escape in development Blockade neutralizing antibodies restores enhances anti-tumor immunity, achieving remarkable success therapy. Therefore, mechanisms cancers attracted an increasing attention. This article aims provide a comprehensive review roles signaling human autoimmune diseases cancers. We summarize all aspects underlying expression cancers, including genetic, epigenetic, post-transcriptional post-translational mechanisms. In addition, we further progress clinical research on antitumor effects targeting alone combination with other therapeutic approaches, providing new strategies for finding tumor markers developing combined approaches.

Language: Английский

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Strategies to manipulate the performance of aptamers in SELEX, post-SELEX and microenvironment

Biotechnology Advances, Journal Year: 2022, Volume and Issue: 55, P. 107902 - 107902

Published: Jan. 10, 2022

Language: Английский

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A photo-triggered self-accelerated nanoplatform for multifunctional image-guided combination cancer immunotherapy

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 25, 2023

Precise and efficient image-guided immunotherapy holds great promise for cancer treatment. Here, we report a self-accelerated nanoplatform combining an aggregation-induced emission luminogen (AIEgen) hypoxia-responsive prodrug multifunctional combination immunotherapy. The near-infrared AIEgen with methoxy substitution simultaneously possesses boosted fluorescence photoacoustic (PA) brightness the strong light absorption ability, as well amplified type I II photodynamic therapy (PDT) properties via enhanced intersystem crossing process. By formulating high-performance paclitaxel (PTX) into nanoparticles, further camouflaging macrophage cell membrane, tumor-targeting theranostic agent is built. integration of PA imaging helps to delineate tumor site sensitively, providing accurate guidance light-induced PDT effect could consume local oxygen lead severer hypoxia, accelerating release PTX drug. As result, chemotherapy induces immunogenic death, which not only elicit antitumor immunity suppress primary tumor, but also inhibit growth distant in 4T1 tumor-bearing female mice. strategy develop agents rational molecular design boosting

Language: Английский

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Semiconducting Polymer Nanoparticles with Surface‐Mimicking Protein Secondary Structure as Lysosome‐Targeting Chimaeras for Self‐Synergistic Cancer Immunotherapy

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(31)

Published: June 15, 2022

Immunotherapy has received tremendous attention for tumor treatment, but the efficacy is greatly hindered by insufficient tumor-infiltration of immune cells and immunosuppressive microenvironment. The strategy that can efficiently activate cytotoxic T lymphocytes inhibit negative regulators will amplify immunotherapy outcome, which however very rare. Herein, a new kind semiconducting polymer (SP) nanoparticles developed, featured with surface-mimicking protein secondary structure (SPSS NPs) self-synergistic cancer combining immunogenic cell death (ICD) checkpoint blockade therapy. SPs excellent photodynamic property are synthesized rational fluorination, massively induce ICD. Additionally, peptide antagonists introduced self-assembled into β-sheet structures on NP surface via preparation process optimization, function as efficient lysosome-targeting chimaeras (LYTACs) to mediate degradation programmed ligand-1 (PD-L1) in lysosome. In vivo experiments demonstrate SPSS NPs not only elicit strong antitumor immunity suppress both primary distant tumor, also evoke long-term immunological memory against rechallenge. This work introduces robust agents well-designed photosensitizer-based ICD induction structures-mediated LYTAC-like multivalence PD-L1 blockade, rendering great promise synergistic immunotherapy.

Language: Английский

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An Activatable Near‐Infrared Afterglow Theranostic Prodrug with Self‐Sustainable Magnification Effect of Immunogenic Cell Death

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(40)

Published: Aug. 2, 2022

Abstract Herein, we report an activatable near‐infrared (NIR) afterglow theranostic prodrug that circumvents high background noise interference caused by external light excitation. The can release hydroxycamptothecin (HCPT) in response to the intratumoral peroxynitrite level associated with immunogenic cell death (ICD), and synchronously activate signal monitor drug process cold‐to‐hot tumor transformation. itself is ICD inducer achieved photodynamic therapy (PDT). PDT initiates recruits first‐arrived neutrophils secrete trigger HCPT release. Intriguingly, demonstrate significantly amplify PDT‐mediated process. thus shows a self‐sustainable magnification effect establishing “ICD‐HCPT release‐amplified ICD” cycling loop. In vivo studies eradicate existing tumors prevent further recurrence through antitumor immune response.

Language: Английский

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Recent progress of aptamer‒drug conjugates in cancer therapy

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(4), P. 1358 - 1370

Published: Jan. 26, 2023

Aptamers are single-stranded DNA or RNA sequences that can specifically bind with the target protein molecule

Language: Английский

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