PLK1 and EGFR targeted nanoparticle as a radiation sensitizer for non-small cell lung cancer

Reda, Moataz; Ngamcherdtrakul, Worapol; Gu, Shenda; Bejan, Daniel S.; Siriwon, Natnaree; Gray, Joe W.; Yantasee, Wassana

doi:10.1016/j.canlet.2019.09.014

Cited by 56 publications

(47 citation statements)

References 47 publications

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“…The synergistic use of radiosensitizers and C-siPLK1-NP can enhance antitumor ability. In addition, the treatment results of C-siPLK1-NP in an orthotopic lung tumor model show that the application of C-siPLK1-NP can effectively inhibit tumor growth and prolong survival time [93].…”

Section: Active Targeting Of Nanomedicines For Lung Cancermentioning

confidence: 99%

Recent applications and strategies in nanotechnology for lung diseases

et al. 2021

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Lung diseases, including COVID-19 and lung cancers, is a huge threat to human health. However, for the treatment and diagnosis of various lung diseases, such as pneumonia, asthma, cancer, and pulmonary tuberculosis, are becoming increasingly challenging. Currently, several types of treatments and/or diagnostic methods are used to treat lung diseases; however, the occurrence of adverse reactions to chemotherapy, drug-resistant bacteria, side effects that can be significantly toxic, and poor drug delivery necessitates the development of more promising treatments. Nanotechnology, as an emerging technology, has been extensively studied in medicine. Several studies have shown that nano-delivery systems can significantly enhance the targeting of drug delivery. When compared to traditional delivery methods, several nanoparticle delivery strategies are used to improve the detection methods and drug treatment efficacy. Transporting nanoparticles to the lungs, loading appropriate therapeutic drugs, and the incorporation of intelligent functions to overcome various lung barriers have broad prospects as they can aid in locating target tissues and can enhance the therapeutic effect while minimizing systemic side effects. In addition, as a new and highly contagious respiratory infection disease, COVID-19 is spreading worldwide. However, there is no specific drug for COVID-19. Clinical trials are being conducted in several countries to develop antiviral drugs or vaccines. In recent years, nanotechnology has provided a feasible platform for improving the diagnosis and treatment of diseases, nanotechnology-based strategies may have broad prospects in the diagnosis and treatment of COVID-19. This article reviews the latest developments in nanotechnology drug delivery strategies in the lungs in recent years and studies the clinical application value of nanomedicine in the drug delivery strategy pertaining to the lung.

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Section: Active Targeting Of Nanomedicines For Lung Cancermentioning

confidence: 99%

Recent applications and strategies in nanotechnology for lung diseases

et al. 2021

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“…We and others have previously reported that PLK1 inhibition or knock-down results in cell cycle arrest in G2/M leading to cancer cell death. [13][14][15] Herein, we found that PLK1 knockdown also results in an increase in PD-L1 surface expression in both human (A549) and murine (LLC-JSP) lung cancer cell lines. As shown in Fig.…”

Section: Plk1 Inhibition Upregulates Pd-l1 Expressionmentioning

confidence: 77%

“…Thus, targeting PLK1 may provide a therapeutic strategy to enhance anti-tumor immunity. Indeed, inhibition of PLK1 results in reduced phosphorylation of STAT3, 14,27 thereby dampening its activity in NSCLC cells. Furthermore, PLK1 inhibition has been shown to increase MHC Class I expression on multiple cell lines, 26 suggesting a role in adaptive immunity.…”

Section: Discussionmentioning

confidence: 99%

“…The same nanoparticle platform has been proven effective for targeted delivery of siRNA to breast tumors and lung tumors in our prior work. [12][13][14]17 Volasertib (iPLK1) was loaded onto mesoporous silica nanoparticle (MSNP) core prior to surface modi cation with polyethylenimine (PEI), polyethylene glycol (PEG), and PD-L1 antibody (Fig. 3A).…”

Section: Pd-l1 Antibody Conjugated Nanoparticles For Delivery Of Plk1mentioning

confidence: 99%

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Development of novel immunotherapy based on nanoparticle co-delivering PLK1 and PD-L1 inhibitors for lung cancer treatment

Reda

Ngamcherdtrakul

Siriwon

et al. 2021

Preprint

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Immune checkpoint inhibitors (ICIs) targeting PD-L1 and PD-1 have improved survival in a subset of patients with advanced non-small cell lung cancer (NSCLC). However, only a minority of NSCLC patients respond to ICIs, highlighting the need for superior immunotherapy. Herein, we developed a nanoparticle-based immunotherapy termed ARAC (Antigen Release Agent and Checkpoint Inhibitor) to enhance the efficacy of PD-L1 inhibitor. ARAC is nanoparticle co-delivering PLK1 inhibitor, volasertib, and PD-L1 antibody. PLK1 is a key mitotic kinase that is overexpressed in various cancers including NSCLC and drives cancer growth. Inhibition of PLK1 selectively kills cancer cells and upregulates PD-L1 expression in surviving cancer cells thereby providing opportunity for ARAC targeted delivery in a positive feedback manner. ARAC reduced effective doses of volasertib and PD-L1 antibody by 5-fold in a metastatic lung tumor model and the effect was mainly mediated by CD8 + T cells. We also observed abscopal effect of ARAC in bilateral NSCLC tumor model and achieved complete cures in some mice when incorporating immune-stimulant CpG onto ARAC. Further, ARAC was well-tolerated in non-human primates. This study highlights a rationale combination strategy to augment existing therapies by utilizing our nanoparticle platform that can load multiple cargo types at once.

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“…Via EGFR + NSCLC cells targeting, the MSNs displayed reduction of PLK1 expression and leading to G2/M arrest. In an orthotopic lung tumor model, reduction of tumor growth and prolonged survival was shown (Reda et al, 2019). Fangman et al designed MSNs loaded with bioreducible mer‐[Ru(III)Cl3(dmso)(L)] prodrugs with highly DNA binding affinity in response to TME.…”

Section: Deliver Drugs For Lung Cancer By Nanomaterialsmentioning

confidence: 99%

Nanomedicine in lung cancer: Current states of overcoming drug resistance and improving cancer immunotherapy

Wang

Hao

Liu

et al. 2020

WIREs Nanomed Nanobiotechnol

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Lung cancer is considered to cause the most cancer‐related deaths worldwide. Due to the deficiency in early‐stage diagnostics and local invasion or distant metastasis, the first line of treatment for most patients unsuitable for surgery is chemotherapy, targeted therapy or immunotherapy. Nanocarriers with the function of improving drug solubility, in vivo stability, drug distribution in the body, and sustained and targeted delivery, can effectively improve the effect of drug treatment and reduce toxic and side effects, and have been used in clinical treatment for lung cancer and many types of cancers. Here, we review nanoparticle (NP) formulation for lung cancer treatment including liposomes, polymers, and inorganic NPs via systemic and inhaled administration, and highlight the works of overcoming drug resistance and improving cancer immunotherapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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PLK1 and EGFR targeted nanoparticle as a radiation sensitizer for non-small cell lung cancer

Cited by 56 publications

References 47 publications

Recent applications and strategies in nanotechnology for lung diseases

Recent applications and strategies in nanotechnology for lung diseases

Development of novel immunotherapy based on nanoparticle co-delivering PLK1 and PD-L1 inhibitors for lung cancer treatment

Nanomedicine in lung cancer: Current states of overcoming drug resistance and improving cancer immunotherapy

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