Antitumor and antimetastatic effects of pemetrexed-loaded targeted nanoparticles in B<sub>16</sub> bearing mice

Lu, Nannan; Li, Rutian; Liu, Qin; Hu, Bing; Xu, Xiaoling; Ji, Cheng; Han, Xinghua; Wang, Pin; Liu, Baorui

doi:10.3109/10717544.2015.1033794

Cited by 12 publications

(4 citation statements)

References 42 publications

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“…Furthermore, due to its low molecular, PMX would be quickly eliminated from neoplastic tissue to blood circulation after administration (Ando et al, 2015 ). Recently, considerable efforts have been directed toward novel PMX delivery systems to achieve the desired therapeutic effect, such as nanoparticles (Lu et al, 2016 ), prodrug (Chan et al, 2014 ) and liposomes (Ando et al, 2015 ). However, co-delivery nanocarriers of multiple target and self-targeting synergistic antitumor effects have not been reported before.…”

Section: Introductionmentioning

confidence: 99%

Development of dual-drug-loaded stealth nanocarriers for targeted and synergistic anti-lung cancer efficacy

et al. 2018

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Combination chemotherapy is widely exploited for suppressing drug resistance and achieving synergistic anticancer efficacy in the clinic. In this paper, the nanostructured targeting methotrexate (MTX) plus pemetrexed (PMX) chitosan nanoparticles (CNPs) were developed by modifying methoxy polye (thylene glycol) (mPEG), in which PEGylation CNPs was used as stealth nanocarriers (PCNPs) and MTX was employed as a targeting ligand and chemotherapeutic agent as well. Studies were undertaken on human lung adenocarcinoma epithelial (A549) and Lewis lung carcinoma (LLC) cell lines, revealing the anti-tumor efficacy of nanoparticle drug delivery system. The co-delivery nanoparticles (MTX-PMX-PCNPs) had well-dispersed with sustained release behavior. Cell counting kit-8 (CCK8) has been used to measure A549 cell viability and the research showed that MTX-PMX-PCNPs were much more effective than free drugs when it came to the inhibition of growth and proliferation. Cell cycle assay by flow cytometry manifested that the MTX-PMX-PCNPs exhibited stronger intracellular taken up ability than free drugs at the same concentration. In vivo anticancer effect results indicated that MTX-PMX-PCNPs exhibited a significantly prolong blood circulation, more tumoral location accumulation, and resulted in a robust synergistic anticancer efficacy in lung cancer in mice. The results clearly demonstrated that such unique synergistic anticancer efficacy of co-delivery of MTX and PMX via stealth nanocarriers, providing a prospective strategy for lung cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Development of dual-drug-loaded stealth nanocarriers for targeted and synergistic anti-lung cancer efficacy

et al. 2018

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“…With the advances in science and biotechnology, the level of early diagnosis for GC has been improved to certain extent, which, in turn, significantly improves its five-year survival rate. Even so, the five-year survival rate of advanced GC is only about 29.3%, which is due to that GC is prone to relapse and metastasis [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

A Novel Gene Expression-Based Prognostic Scoring System to Predict Survival in Gastric Cancer

Wang¹

2017

Gastroenterology

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Analysis of gene expression patterns in gastric cancer (GC) can help to identify a comprehensive panel of gene biomarkers for predicting clinical outcomes and to discover potential new therapeutic targets. Here, a multi-step bioinformatics analytic approach was developed to establish a novel prognostic scoring system for GC. We first identified 276 genes that were robustly differentially expressed between normal and GC tissues, of which, 249 were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. The biological functions of 249 genes are related to cell cycle, RNA/ncRNA process, acetylation and extracellular matrix organization. A network was generated for view of the gene expression architecture of 249 genes in 265 GCs. Finally, we applied a canonical discriminant analysis approach to identify a 53-gene signature and a prognostic scoring system was established based on a canonical discriminant function of 53 genes. The prognostic scores strongly predicted patients with GC to have either a poor or good OS. Our study raises the prospect that the practicality of GC patient prognosis can be assessed by this prognostic scoring system.

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“…However, the drug runs into toxicity issues at higher doses . To address this issue, PEM has been formulated with various carriers and delivery strategies. ,− The drug itself has higher affinity for the alpha-folate receptor than FA and similar affinity to raltitrexed and methotrexate in L1210 cells …”

Section: Introductionmentioning

confidence: 99%

Development of a Pemetrexed/Folic Acid Nanoformulation: Synthesis, Characterization, and Efficacy in a Murine Colorectal Cancer Model

et al. 2020

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The folate analogue pemetrexed (PEM) is an approved therapeutic for non-small cell lung cancer and malignant pleural mesothelioma with the potential for broader application in combination therapies. Here, we report the development of a nanoformulation of PEM and its efficacy against the CT26 murine colorectal cancer cell line in vitro and in vivo. Utilizing layer-by-layer deposition, we integrate PEM, along with folic acid (FA), onto a fluorescent polystyrene nanoparticle (NP) substrate. The final nanoformulation (PEM/FA-NP) has a size of ∼40 nm and a zeta potential of approximately −20 mV. Cell uptake studies indicated increased uptake in vitro for the PEM/FA-NP compared to the uncoated NP, likely due to the presence of PEM and FA. Viability studies were performed to determine the potency of the PEM/FA-NP formulation against CT26 cells. Syngeneic CT26 tumors in BALB/c mice showed reduced growth when treated once daily (2.1 mg/kg PEM) for 3 days with PEM/FA-NP versus the vehicle (uncoated) control, with no observable signs of systemic toxicity associated with the nanoformulation. Although the current study size is limited (n = 4 animals for each group), the overall performance and biocompatibility of the PEM/FA-NP observed suggest that further optimization and larger-scale studies may be warranted for this novel formulation.

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Antitumor and antimetastatic effects of pemetrexed-loaded targeted nanoparticles in B₁₆ bearing mice

Cited by 12 publications

References 42 publications

Development of dual-drug-loaded stealth nanocarriers for targeted and synergistic anti-lung cancer efficacy

Development of dual-drug-loaded stealth nanocarriers for targeted and synergistic anti-lung cancer efficacy

A Novel Gene Expression-Based Prognostic Scoring System to Predict Survival in Gastric Cancer

Development of a Pemetrexed/Folic Acid Nanoformulation: Synthesis, Characterization, and Efficacy in a Murine Colorectal Cancer Model

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Antitumor and antimetastatic effects of pemetrexed-loaded targeted nanoparticles in B16 bearing mice

Cited by 12 publications

References 42 publications

Development of dual-drug-loaded stealth nanocarriers for targeted and synergistic anti-lung cancer efficacy

Development of dual-drug-loaded stealth nanocarriers for targeted and synergistic anti-lung cancer efficacy

A Novel Gene Expression-Based Prognostic Scoring System to Predict Survival in Gastric Cancer

Development of a Pemetrexed/Folic Acid Nanoformulation: Synthesis, Characterization, and Efficacy in a Murine Colorectal Cancer Model

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Antitumor and antimetastatic effects of pemetrexed-loaded targeted nanoparticles in B₁₆ bearing mice