Folate-conjugated zein/Fe3O4 nanocomplexes for the enhancement of cellular uptake and cytotoxicity of gefitinib

Pang, Jiafeng; Li, Zhixian; Li, Shaomin; Lin, Shuying; Wang, Hongdi; Xie, Qiuling; Jiang, Yanbin

doi:10.1007/s10853-018-2684-7

Cited by 20 publications

(18 citation statements)

References 45 publications

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“…The EE of ZAuNPs and ZNPs were calculated as (34 ± 2) % and (30 ± 2) % for the 50 µg/mL formulations, respectively ( Figure S6 ), as described in the Materials and Methods section [ 27 ]. While the loading of Irinotecan into ZNP and ZAuNP has not yet been reported, the more hydrophobic and potent analogue (SN38) has achieved higher EEs in ZNP samples [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

Gold–Protein Composite Nanoparticles for Enhanced X-ray Interactions: A Potential Formulation for Triggered Release

et al. 2021

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Drug-delivery vehicles have been used extensively to modulate the biodistribution of drugs for the purpose of maximizing their therapeutic effects while minimizing systemic toxicity. The release characteristics of the vehicle must be balanced with its encapsulation properties to achieve optimal delivery of the drug. An alternative approach is to design a delivery vehicle that preferentially releases its contents under specific endogenous (e.g., tissue pH) or exogenous (e.g., applied temperature) stimuli. In the present manuscript, we report on a novel delivery system with potential for triggered release using external beam radiation. Our group evaluated Zein protein as the basis for the delivery vehicle and used radiation as the exogenous stimulus. Proteins are known to react with free radicals, produced during irradiation in aqueous suspensions, leading to aggregation, fragmentation, amino acid modification, and proteolytic susceptibility. Additionally, we incorporated gold particles into the Zein protein matrix to create hybrid Zein–gold nanoparticles (ZAuNPs). Zein-only nanoparticles (ZNPs) and ZAuNPs were subsequently exposed to kVp radiation (single dose ranging from 2 to 80 Gy; fractionated doses of 2 Gy delivered 10 times) and characterized before and after irradiation. Our data indicated that the presence of gold particles within Zein particles was correlated with significantly higher levels of alterations to the protein, and was associated with higher rates of release of the encapsulated drug compound, Irinotecan. The aggregate results demonstrated a proof-of-principle that radiation can be used with gold nanoparticles to modulate the release rates of protein-based drug-delivery vehicles, such as ZNPs.

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Section: Resultsmentioning

confidence: 99%

Gold–Protein Composite Nanoparticles for Enhanced X-ray Interactions: A Potential Formulation for Triggered Release

et al. 2021

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“…Colloidal stability of PTX/Zein-FA was investigated by observing the particle size, zeta potential, and PDI of freeze-dried form of PTX/Zein-FA under the storage temperatures of 4 and 25 °C over a period of 45 days. DLS analysis showed that PTX/Zein-FA had excellent physical stability (Figure S2), due to the stabilizing effect of surfactants and negative charge of nanoparticles [45,46]. LC and EE of the nanoparticles were determined in both targeted and non-targeted nanoparticles (Figure 2D).…”

Section: Resultsmentioning

confidence: 99%

Development of Folate-Functionalized PEGylated Zein Nanoparticles for Ligand-Directed Delivery of Paclitaxel

Soe

Gautam

et al. 2019

Pharmaceutics

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In this study, we investigated the active targeted delivery of a hydrophobic drug, paclitaxel (PTX), via receptor-mediated endocytosis by folate receptors expressed on cancer cells using a protein-based nanoparticle system. PTX was loaded on zein nanoparticles and conjugated with folate (PTX/Zein-FA) to estimate its chemotherapeutic efficacy in folate receptor-expressing KB cancer cells. PTX/Zein-FA nanoparticles were successfully developed, with a nanoparticle size of ~180 nm and narrow polydispersity index (~0.22). Accelerated release of PTX in an acidic environment was observed for PTX/Zein-FA. An in vitro cellular study of PTX/Zein-FAs in KB cells suggested that PTX/Zein-FA improved the cytotoxic activity of PTX on folate receptors overexpressed in cancer cells by inducing proapoptotic proteins and inhibiting anti-apoptotic proteins. In addition, PTX/Zein-FA exhibited anti-migratory properties and could alter the cell cycle profile of KB cells. A549 cells, which are folate receptor-negative cancer cells, showed no significant enhancement in the in vitro cellular activities of PTX/Zein-FA. We describe the antitumor efficacy of PTX/Zein-FA in KB tumor-bearing mice with minimum toxicity in healthy organs, and the results were confirmed in comparison with free drug and non-targeted nanoparticles.

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“…Therefore, we suspected that DM1-loaded ZNPs enter cells by an endocytosis pathway, which might be internalized more quickly than free DM1 via active transport. But, this enhancement effect was saturated after the nanoparticles reach a certain number (Zou & Gu, 2013;Pang et al, 2018). So that, the cytotoxicity of the DM1-loaded ZNPs is stronger than that of the free DM1 at low doses, and their cytotoxicity tends to be uniform with increasing dose.…”

Section: Discussionmentioning

confidence: 99%

“…Nanodrug delivery systems are capable of prolonging blood circulation time, numerous renewable sources, high drug-binding, improving drug solubilization, and accumulating at a tumor via the enhanced permeability and retention (EPR) effect (Elzoghby et al, 2017;Pang et al, 2018). Zein, for this purpose, could be a good carrier in this system due to its inherent biocompatibility, nontoxicity, in vivo biodegradability and the capacity of self-assembly (Chen et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…It is classified as one of the safest biomaterial excipients by the US FDA (Labib, 2018). Moreover, compared with other proteins, zein has larger proportion of hydrophobic amino acid, which leads to higher potential for hydrophobic drug loading and self-assembling into stable nanoparticles without the use of toxic chemical crosslinkers (Labib, 2018;Pang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

Drug Delivery

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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

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Folate-conjugated zein/Fe3O4 nanocomplexes for the enhancement of cellular uptake and cytotoxicity of gefitinib

Cited by 20 publications

References 45 publications

Gold–Protein Composite Nanoparticles for Enhanced X-ray Interactions: A Potential Formulation for Triggered Release

Gold–Protein Composite Nanoparticles for Enhanced X-ray Interactions: A Potential Formulation for Triggered Release

Development of Folate-Functionalized PEGylated Zein Nanoparticles for Ligand-Directed Delivery of Paclitaxel

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

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