Development of a nanoparticle-based immunotherapy targeting PD-L1 and PLK1 for lung cancer treatment

Reda, Moataz; Ngamcherdtrakul, Worapol; Nelson, Molly A.; Siriwon, Natnaree; Wang, Ruijie; Zaidan, Husam Y.; Bejan, Daniel S.; Reda, Sherif; Hoang, Ngoc Ha; Crumrine, Noah; Rehwaldt, Justin P. C.; Bindal, Akash; Mills, Gordon B.; Gray, Joe W.; Yantasee, Wassana

doi:10.1038/s41467-022-31926-9

Cited by 77 publications

(43 citation statements)

References 49 publications

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“…The spatial interplay of immune cells and other cells in the TME determines the immune response against tumors ( Petitprez et al, 2020 ). As immunotherapy of tumors has been intensively studied, immune checkpoint inhibitors (ICIs) against tumor immune escape are expected to be an essential strategy to improve the prognosis of lung adenocarcinoma patients ( Qiao et al, 2021 ; Liu et al, 2022 ; Reda et al, 2022 ). However, due to the heterogeneity and complexity of the TME, patients with the same pathological stage may also exhibit different TME characteristics, resulting in different therapeutic effects upon immunotherapy ( Bagaev et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinoma

et al. 2022

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Background: Tumor-associated macrophages as important members of the tumor microenvironment, are highly plastic and heterogeneous. TAMs can be classified into two preliminary subtypes: M1 and M2 macrophages. M2 macrophages are significantly associated with the progression of lung adenocarcinoma. However, no study has investigated the heterogeneity among M2 macrophages and their differentiation-related genes at the single-cell level to guide the clinical treatment of lung adenocarcinoma.Methods: Using the available annotation information from the Tumor Immune Single-cell Hub database, we clustered and annotated 12 lung adenocarcinoma samples using the R package ‘Seurat’. Subsequently, we extracted M2 macrophages for secondary clustering analysis and performed cell trajectory analysis using the R package ‘monocle2’. Based on heterogeneous genes associated with the differentiation trajectory of M2 macrophages, we established a prognostic lung adenocarcinoma model using Lasso-Cox and multivariate stepwise regression. In addition, we also performed immunotherapy and chemotherapy predictions.Results: M2 macrophages exhibit heterogeneity among themselves. M2 macrophages in different differentiation states showed significant differences in pathway activation and immune cell communication. Prognostic signature based on heterogeneous genes can be used to classify the prognostic status and abundance of immune cell infiltration in lung adenocarcinoma patients. In addition, the calculation of the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and the validation of the GSE126044 database indicated that lung adenocarcinoma patients with high-risk scores had poorer treatment outcomes when receiving immune checkpoint inhibitors treatment.Conclusion: Based on scRNA-seq and Bulk-seq data, we identified M2 macrophage-associated prognostic signature with a potential clinical utility to improve precision therapy.

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Section: Discussionmentioning

confidence: 99%

Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinoma

et al. 2022

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“…Copyright 2019, American Chemical Society. (E) Synthesis scheme of PD-L1 antibody conjugated NP for delivering PLK1 inhibitor volasertib ( 98 ). (F) Proposed mechanism of action of ARAC nano construct ( 98 ).…”

Section: Nanotechnology-based Therapeutics For Lung Cancermentioning

confidence: 99%

“…(E) Synthesis scheme of PD-L1 antibody conjugated NP for delivering PLK1 inhibitor volasertib ( 98 ). (F) Proposed mechanism of action of ARAC nano construct ( 98 ). Adapted with permissions from ref ( 98 ).…”

Section: Nanotechnology-based Therapeutics For Lung Cancermentioning

confidence: 99%

Section: Nanotechnology-based Therapeutics For Lung Cancermentioning

confidence: 99%

“…(d) Kaplan–Meier Survival curve (mice were euthanized when a combined tumor size reached 2000 mm3). ** P = 0.0036 for ARAC vs. saline (Log-rank Mantel–Cox test) ( 98 ). Adapted with permissions from ref ( 98 ).…”

Section: Nanotechnology-based Therapeutics For Lung Cancermentioning

confidence: 99%

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Advanced diagnostic and therapeutic strategies in nanotechnology for lung cancer

et al. 2022

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As a highly invasive thoracic malignancy with increasing prevalence, lung cancer is also the most lethal cancer worldwide due to the failure of effective early detection and the limitations of conventional therapeutic strategies for advanced-stage patients. Over the past few decades, nanotechnology has emerged as an important technique to obtain desired features by modifying and manipulating different objects on a molecular level and gained a lot of attention in many fields of medical applications. Studies have shown that in lung cancer, nanotechnology may be more effective and specific than traditional methods for detecting extracellular cancer biomarkers and cancer cells in vitro, as well as imaging cancer in vivo; Nanoscale drug delivery systems have developed rapidly to overcome various forms of multi-drug resistance and reduce detrimental side effects to normal tissues by targeting cancerous tissue precisely. There is no doubt that nanotechnology has the potential to enhance healthcare systems by simplifying and improving cancer diagnostics and treatment. Throughout this review, we summarize and highlight recent developments in nanotechnology applications for lung cancer in diagnosis and therapy. Moreover, the prospects and challenges in the translation of nanotechnology-based diagnostic and therapeutic methods into clinical applications are also discussed.

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Mesoporous Silica Nanoparticles as an Ideal Platform for Cancer Immunotherapy: Recent Advances and Future Directions.

Godakhindi,

Tarannum,

Dam

et al. 2024

Adv Healthcare Materials

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Cancer immunotherapy has recently transformed the traditional approaches against various cancer malignancies. Immunotherapy includes systemic and local treatments to enhance immune responses against cancer; and involves strategies such as immune checkpoints, cancer vaccines, immune modulatory agents, mimetic antigen‐presenting cells, and adoptive cell therapy. Despite promising results, these approaches still suffer from several limitations including a lack of precise delivery of immune‐modulatory agents to the target cells, off‐target toxicity, among others that can be overcome using nanotechnology. Mesoporous silica nanoparticles (MSNs) have been investigated to improve various aspects of cancer immunotherapy attributed to the advantageous structural features of this nanomaterial. MSNs can be engineered to alter their properties such as size, shape, porosity, surface functionality, and adjuvanticity. This review explores the immunological properties of MSNs; and the use of MSNs as delivery vehicles for immune‐adjuvants, vaccines, and mimetic antigen‐presenting cells (APCs). The review also details the current strategies to remodel the tumor microenvironment to positively reciprocate towards the anti‐tumor immune cells and the use of MSNs for immunotherapy in combination with other anti‐tumor therapies including photodynamic/thermal therapies to enhance the therapeutic effect against cancer. Lastly, the present demands and future scenarios for the use of MSNs for cancer immunotherapy are discussed.This article is protected by copyright. All rights reserved

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Development of a nanoparticle-based immunotherapy targeting PD-L1 and PLK1 for lung cancer treatment

Cited by 77 publications

References 49 publications

Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinoma

Integration of single-cell and bulk RNA-seq to establish a predictive signature based on the differentiation trajectory of M2 macrophages in lung adenocarcinoma

Advanced diagnostic and therapeutic strategies in nanotechnology for lung cancer

Mesoporous Silica Nanoparticles as an Ideal Platform for Cancer Immunotherapy: Recent Advances and Future Directions.

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