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

Abstract Background Biomimetic nanotechnology-based RNA interference (RNAi) has been successful in improving theranostic efficacy in malignant tumors. Its integration with hybrid biomimetic membranes made of natural cell membranes fused with liposomal membranes is mutually beneficial and extends their biofunctions. However, limited research has focused on engineering such biomimetics to endow them with unique properties and functions, in particular, those essential for a “smart” drug delivery system, such as a tumor microenvironment (TME)-activated multifunctional biomimetic nanoplatform. Results Herein, we utilized an integrated hybrid nanovesicle composed of cancer cell membranes (Cm) and matrix metallopeptidase 9 (MMP-9)-switchable peptide-based charge-reversal liposome membranes (Lipm) to coat lipoic acid-modified polypeptides (LC) co-loaded with phosphoglycerate mutase 1 (PGAM1) siRNA (siPGAM1) and DTX. The nanovesicle presented a negatively charged coating (citraconic anhydride-grafted poly-l-lysine, PC) in the middle layer for pH-triggered charge conversion functionalization. The established chemotherapeutic drug (DTX) co-delivery system CLip-PC@CO-LC nanoparticles (NPs) have a particle size of ~ 193 nm and present the same surface proteins as the Cm. Confocal microscopy and flow cytometry results indicated a greater uptake of MMP-9-treated CLip-PC@CO-LC NPs compared with that of the CLip-PC@CO-LC NPs without MMP-9 pretreatment. The exposure to MMP-9 activated positively charged cell-penetrating peptides on the surface of the hybrid nanovesicles. Moreover, pH triggered membrane disruption, and redox triggered DTX and siRNA release, leading to highly potent target-gene silencing in glycolysis and chemotherapy with enhanced antiproliferation ability. The biodistribution results demonstrated that the CLip-PC@LC-DiR NPs accumulated in the tumor owing to a combination of long blood retention time, homologous targeting ability, and TME-activated characteristics. The CLip-PC@CO-LC NPs led to more effective tumor growth inhibition than the DTX and free siPGAM1 formulations. Conclusions TME-activated cancer cell membrane-liposome integrated hybrid NPs provide an encouraging nanoplatform that combines RNAi with chemotherapy for precise treatment of non-small cell lung cancer. Graphical abstract

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Construction of a Supramolecular Drug–Drug Delivery System for Non-Small-Cell Lung Cancer Therapy

ACS Applied Materials & Interfaces ◽

10.1021/acsami.7b07565 ◽

2017 ◽

Vol 9 (35) ◽

pp. 29505-29514 ◽

Cited By ~ 33

Author(s):

Zhihao Zhang ◽

Leilei Shi ◽

Chenwei Wu ◽

Yue Su ◽

Jiwen Qian ◽

...

Keyword(s):

Lung Cancer ◽

Drug Delivery ◽

Cancer Therapy ◽

Small Cell Lung Cancer ◽

Drug Delivery System ◽

Delivery System ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Lung Cancer Therapy

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Efficient cocktail chemotherapy by co-delivery of a hydrogen sulfide-releasing aspirin prodrug and paclitaxel via single nanoparticles

RSC Advances ◽

10.1039/c6ra28142g ◽

2017 ◽

Vol 7 (22) ◽

pp. 13458-13466 ◽

Cited By ~ 2

Author(s):

Lulu Cai ◽

Lin He ◽

Yan Wang ◽

Jian Zhong ◽

Chengjian Zhao ◽

...

Keyword(s):

Lung Cancer ◽

Hydrogen Sulfide ◽

Small Cell Lung Cancer ◽

Delivery System ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung

A cocktail composed of hydrogen sulfide-releasing aspirin (HS-ASP) and paclitaxel (PTX) in a single delivery system was formulated and provides a promising platform for the cocktail treatment of non-small cell lung cancer.

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Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and siRNA for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and EGFR Mutations

Pharmaceutics ◽

10.3390/pharmaceutics13071063 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1063

Author(s):

Joydeb Majumder ◽

Tamara Minko

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Delivery System ◽

Cell Lung Cancer ◽

Targeted Delivery ◽

Small Cell ◽

Egfr Mutations ◽

Small Cell Lung ◽

Intrinsic Resistance ◽

Resistance To Chemotherapy

Resistance to chemotherapy, enhanced proliferation, invasion, angiogenesis, and metastasis (RPIAM) represent major obstacles that limit the efficacy of cancer treatment especially in advanced stages of cancer. Overcoming or suppressing RPIAM can dramatically improve the treatment outcome. Non-small cell lung cancer (NSCLC) is frequently diagnosed in an advanced stage and often possesses intrinsic resistance to chemotherapy accompanied by the fast development of acquired resistance during the treatment. Oncogenic receptor tyrosine kinases (TKs), specifically epidermal growth factor (EGF) TKs, play an important role in the activation of MAPK/PI3K/Akt/STAT pathways, finally leading to the development of RPIAM. However, the suppression of EGF-TK by different drugs is limited by various defensive mechanisms and mutations. In order to effectively prevent the development of RPIAM in NSCLC, we formulated and tested a multicomponent and multifunctional cancer targeted delivery system containing Nanostructured Lipid Carriers (NLCs) as vehicles, luteinizing hormone release hormone (LHRH) as a cancer targeting moiety, EFG-TK inhibitor gefitinib and/or paclitaxel as anticancer drug(s), siRNA targeted to EGF receptor (EGFR) mRNA as a suppressor of EGF receptors, and an imaging agent (rhodamine) for the visualization of cancer cells. Experimental data obtained show that this complex delivery system possesses significantly enhanced anticancer activity that cannot be achieved by individual components applied separately.

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