Chitosan surface modified PLGA nanoparticles loaded with brigatinib for the treatment of non-small cell lung cancer

Abstract In the current study, surface-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) of brigatinib (BRB) were prepared by studying the variables PLGA (polymer), PVA (stabilizer) and chitosan (coater) against experimentally obtained responses. The optimized NPs (F2) were evaluated in vitro for differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), particle size, polydispersity index (PDI) and drug entrapment (EE), in vitro release, hematocompatibility and in vitro anticancer studies. The optimized NPs’ (F2) composition, PLGA (75 mg), PVA (0.55% w/v), chitosan (0.75% w/v) and 30 mg of BRB was found to be optimum with particle size (406.3 ± 5.1 nm), PDI (0.277), ζ potential (30.4 ± 3.3 mV) and %EE (82.32%). The in vitro release profile showed a sustained release pattern of the F2 nanoparticles of BRB. The 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay revealed a significant anticancer activity for F2 NPs against A549 cell lines in comparison to free BRB. The result obtained in this work indicated the immense potential of nanoparticles to effectively deliver the BRB to the cancer site for the treatment of non-small cell lung cancer.

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Afatinib-loaded inhalable PLGA nanoparticles for localized therapy of non-small cell lung cancer (NSCLC)—development and in-vitro efficacy

Drug Delivery and Translational Research ◽

10.1007/s13346-020-00802-8 ◽

2020 ◽

Cited By ~ 3

Author(s):

Rasha S. Elbatanony ◽

Vineela Parvathaneni ◽

Nishant S. Kulkarni ◽

Snehal K. Shukla ◽

Gautam Chauhan ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Plga Nanoparticles ◽

Small Cell ◽

Small Cell Lung

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Enhanced Antitumor Efficacy of Docetaxel-Loaded Monomethoxy Poly(ethylene glycol)-Poly(D, L-lactide-co-glycolide) Amphiphilic Copolymer Against Non-Small Cell Lung Cancer

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2020.18756 ◽

2020 ◽

Vol 20 (12) ◽

pp. 7263-7270

Author(s):

Yijian Lin ◽

Xibin Zhuang ◽

Baosong Xie ◽

Hanqing Chen

Keyword(s):

Lung Cancer ◽

Drug Delivery ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Side Effect ◽

Therapeutic Efficacy ◽

Plga Nanoparticles ◽

Small Cell ◽

Small Cell Lung

Lung cancer, including non-small cell lung cancer (NSCLC), is one of the mainly diagnosed cancer and becomes as the leading cause of death induced by cancer worldwide. Conventional antitumor drugs, such as docetaxel (DTX), exhibit excellent therapeutic efficacy, however, serious adverse effects have occurred due to their side effect, which limits their clinical use. Therefore, it is necessary to develop the novel drug delivery systems for antitumor therapy. Herein, we successfully developed mPEG-PLGA nanoparticles for the encapsulation of the clinically relevant drug DTX (NP-DTX) via an improved green method by emulsion. The mPEG-PLGA nanoparticles could target A549 and increased the cytotoxicity of DTX, NP-DTX showed significantly enhanced antitumor effect and therapeutic efficacy on NSCLC in vitro and in vivo. Compared with free DTX, NP-DTX significantly inhibited tumor growth and reduced the side effect of DTX. Therefore, we have shown a promising strategy to construct a novel therapeutic platform for targeted anti-tumor drug delivery.

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Investigation of in vitro Activities of Cu2ZnSnS4 Nanoparticles in Human Non-Small Cell Lung Cancer

Materials Today Communications ◽

10.1016/j.mtcomm.2021.102304 ◽

2021 ◽

pp. 102304

Author(s):

Suleyman Gokhan Colak ◽

Canan Vejselova Sezer ◽

Ruken Esra Demirdogen ◽

Mine Ince ◽

Fatih Mehmet Emen ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung

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Elevating CDCA3 levels in non-small cell lung cancer enhances sensitivity to platinum-based chemotherapy

Communications Biology ◽

10.1038/s42003-021-02136-8 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Katrina Kildey ◽

Neha S. Gandhi ◽

Katherine B. Sahin ◽

Esha T. Shah ◽

Eric Boittier ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Genome Instability ◽

Small Cell ◽

Small Cell Lung ◽

Protein Levels ◽

Platinum Based Chemotherapy ◽

Platinum Agents

AbstractPlatinum-based chemotherapy remains the cornerstone of treatment for most non-small cell lung cancer (NSCLC) cases either as maintenance therapy or in combination with immunotherapy. However, resistance remains a primary issue. Our findings point to the possibility of exploiting levels of cell division cycle associated protein-3 (CDCA3) to improve response of NSCLC tumours to therapy. We demonstrate that in patients and in vitro analyses, CDCA3 levels correlate with measures of genome instability and platinum sensitivity, whereby CDCA3high tumours are sensitive to cisplatin and carboplatin. In NSCLC, CDCA3 protein levels are regulated by the ubiquitin ligase APC/C and cofactor Cdh1. Here, we identified that the degradation of CDCA3 is modulated by activity of casein kinase 2 (CK2) which promotes an interaction between CDCA3 and Cdh1. Supporting this, pharmacological inhibition of CK2 with CX-4945 disrupts CDCA3 degradation, elevating CDCA3 levels and increasing sensitivity to platinum agents. We propose that combining CK2 inhibitors with platinum-based chemotherapy could enhance platinum efficacy in CDCA3low NSCLC tumours and benefit patients.

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Inhibition of yes-associated protein suppresses migration, invasion, and metastasis in non-small cell lung cancer in vitro and in vivo

Clinical and Experimental Medicine ◽

10.1007/s10238-021-00738-4 ◽

2021 ◽

Author(s):

Tomoya Takeda ◽

Masanobu Tsubaki ◽

Shuji Genno ◽

Takuya Matsuda ◽

Yuuta Yamamoto ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Invasion And Metastasis ◽

Small Cell Lung

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Mimicking Tumor Hypoxia in Non-Small Cell Lung Cancer Employing Three-Dimensional In Vitro Models

Cells ◽

10.3390/cells10010141 ◽

2021 ◽

Vol 10 (1) ◽

pp. 141

Author(s):

Iwona Ziółkowska-Suchanek

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Tumor Hypoxia ◽

Three Dimensional ◽

In Vitro Models ◽

Small Cell ◽

Small Cell Lung ◽

Multicellular Tumor Spheroid

Hypoxia is the most common microenvironment feature of lung cancer tumors, which affects cancer progression, metastasis and metabolism. Oxygen induces both proteomic and genomic changes within tumor cells, which cause many alternations in the tumor microenvironment (TME). This review defines current knowledge in the field of tumor hypoxia in non-small cell lung cancer (NSCLC), including biology, biomarkers, in vitro and in vivo studies and also hypoxia imaging and detection. While classic two-dimensional (2D) in vitro research models reveal some hypoxia dependent manifestations, three-dimensional (3D) cell culture models more accurately replicate the hypoxic TME. In this study, a systematic review of the current NSCLC 3D models that have been able to mimic the hypoxic TME is presented. The multicellular tumor spheroid, organoids, scaffolds, microfluidic devices and 3D bioprinting currently being utilized in NSCLC hypoxia studies are reviewed. Additionally, the utilization of 3D in vitro models for exploring biological and therapeutic parameters in the future is described.

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Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts

Cell Death and Disease ◽

10.1038/s41419-021-03928-w ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Jianjiao Ni ◽

Xiaofei Zhang ◽

Juan Li ◽

Zhiqin Zheng ◽

Junhua Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Bone Metastasis ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Osteoclast Differentiation ◽

Small Cell ◽

Signalling Pathway ◽

Small Cell Lung

AbstractBone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-β/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC.

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