Zein nanoparticles as nontoxic delivery system for maytansine in the treatment of non-small cell lung cancer

Abstract

2020) Zein nanoparticles as nontoxic delivery system for maytansine in the treatment of non-small cell lung cancer, Drug Delivery, 27:1, 100-109, ABSTRACT Purpose: Maytansine (DM1) is a potent anticancer drug and limited in clinical application due to its poor water solubility and toxic side effects. Zein is widely used in nano drug delivery systems due to its good biocompatibility. In this study, we prepared DM1-loaded zein nanoparticles (ZNPs) to achieve tumor targeting and reduce toxic side effects of DM1. Methods: ZNPs were prepared by phase separation and Box-Behnken design was used to optimize the formulation. Then, confocal fluorescence microscope and flow cytometry were used to determine cellular uptake of ZNPs. A549 cells were cultured in vitro to study cytotoxicity and used to establish tumor xenografts in nude mice. Biodistribution and antitumor activity of ZNPs were performed in vivo experiments. In addition, we also performed histological and immunohistochemical examinations on tumors and viscera. Results: The optimal prescription was obtained by using 120 lL zein added to 2 mL water under stirring in 300 rpm. The encapsulation efficiency and drug loading were 82.97 ± 0.80% and 3.32 ± 0.03%, respectively. We found that DM1-loaded ZNPs have a strong inhibitory effect on A549 cells, which stemmed from the ability of ZNPs to enhance cellular uptake. Furthermore, we demonstrated that DM1-loaded ZNPs exhibits a better antitumor efficacy than DM1, which tumor inhibition rate were 97.3% and 92.7%, respectively. The biodistribution revealed that ZNPs could targeted to tumor. Finally, we confirmed by histological that DM1-loaded ZNPs are nontoxic. Conclusion: DM1-loaded ZNPs have considerable antitumor activity. Thus, DM1-loaded ZNPs are a promising treatment of non-small cell lung cancer. ARTICLE HISTORY

The Yunnan national medicine Maytenus compound inhibits the proliferation of hepatocellular carcinoma (HCC) by suppressing the activation of the EGFR-PI3K-AKT signaling pathway

“…Therefore, as early as the 1970s and 1980s, a great number of clinical studies attempted to apply maytansine to clinical treatments. Unfortunately, positive results for maytansine in the treatment of colorectal cancer 19 and melanoma 20 , lymphoma 21 , breast cancer 22 , small cell lung cancer 23 , soft tissue sarcoma 24 , cervical cancer 25 , and pancreatic cancer 26 were not obtained in phase II clinical studies primarily because maytansine has poor water solubility and high toxicity and is nonselective 18 , 27 , which led to extremely low dose-limiting toxicities (2 mg/m 2 ) in the human body. Therefore, the manifestation of antitumor activity was not possible using a tolerable dose in humans 28 .…”

Surface-Tailored Zein Nanoparticles: Strategies and Applications

“…Application Encapsulated Substance Reference zein/chitosan nano complex oral drug and food delivery curcumin and resveratrol [97] zein/carrageenan oral drug delivery curcumin and piperine coenzyme Q10 and piperine [98,99] hydrophilic whey isolate/zein oral drug delivery curcumin [100] zein/carrageenan/tween 80 drug delivery curcumin [101] pectin from Akebia trifoliata var. Australis fruit peel and zein drug and food delivery curcumin [102] deamidated zein peptide drug and food delivery curcumin [37] zein/soybean polysaccharide drug delivery lutein [103] zein/caseinate oral and parenteral drug delivery simvastatin [44] zein/gold nanoparticles antibacterial and larvicidal the whole nanocomposite [104] zein/lactoferrin drug delivery 7,8-dihydroxyflavone [105] zein/tea saponins food and drug delivery lutein [106] solid zein nanoparticles drug delivery Gene delivery maytansine PTEN and TRAIL genes [107,108] hollow zein nanoparticles food and drug delivery curcumin [109] zein/CMC postharvest fruit preservation natamycin [56] zein/bacterial cellulose preservative and packaging silymarin [110] zein/sodium deoxycholate cytotoxic drug delivery paclitaxel [111] lipid/zein core-shell nanocomposite targeted pulmonary drug delivery all-trans retinoic acid and genistein [112] mesoporous silica nanoparticles coated with zein polycarbolactone mixture antimicrobial photodynamic therapy methylene blue [113] zein/phosphatidylcholine hybrid nanoparticles cancer photodynamic therapy indocyanine green [114] zein/lactoferrin functional food delivery 7,8-dihydroxyflavone [105] zein/hyaluronic acid targeted drug delivery curcumin honokiol [115,116] zein-cellulose nanocrystals core-shell nanoparticles functional food delivery curcumin [117] zein nanoparticles oral drug delivery resveratrol [118] polyamine modified zein pest management avermectin [119] zein/pluronic F68 nanoparticles pest management limonene and carvacrol [120] zein/fucoidan nanocomplex oral drug delivery curcumin…”

Stoichioproteomics study of differentially expressed proteins and pathways in head and neck cancer

“…Among them, three ceRNAs (HCG22, LINC00460 and STC2) LINC00460, HCG22 and STC2 exhibited aberrant levels of expression and significantly correlated with survival (Zhao et al, 2018). However, because of the high costs, only sporadic key proteins were identified by immunohistochemical technologies (Kao and Ulbright, 2020;Yu et al, 2020). Nevertheless, immunohistochemical method is the most accurate proteomics technology, and systematic studies of head and neck cancer based on immunohistochemical data are inadequate.…”