RPV‐modified epirubicin and dioscin co‐delivery liposomes suppress non‐small cell lung cancer growth by limiting nutrition supply

Abstract

| 621 wileyonlinelibrary.com/journal/cas | INTRODUC TI ONLung cancer is one of the most common malignancies and a leading cause of cancer-related death worldwide. 1 Among all lung cancers, approximately 85% are non-small cell lung cancer (NSCLC), for which morbidity is significantly higher than for small cell lung cancer. 2 In the past decade, targeted therapy, immunotherapy, and similar approaches rapidly developed to become the new treatment modalities for NSCLC. Despite recent developments and improvements in diagnosis and treatment, prospects for patients with NSCLC are dismal and the 5-year overall survival rate is only 15%-18%. 3,4 Rapid growth and metastasis are basic biological characteristics of malignant tumors, including NSCLC. 5 It is well known that angiogenesis plays a key role in cancer growth and metastasis. Anti-angiogenesis treatment has evolved to achieve encouraging results, but despite the widespread application of anti-angiogenic drugs, they have not attained satisfactory efficacy. [6][7][8] This means that alternative nutrient supply channels support tumor growth.Vasculogenic mimicry (VM) is defined as formation of vascu- lar-like structures lined with tumor cells without the presenceThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractChemotherapy for non-small cell lung cancer (NSCLC) is far from satisfactory, mainly due to poor targeting of antitumor drugs and self-adaptations of the tumors.Angiogenesis, vasculogenic mimicry (VM) channels, migration, and invasion are the main ways for tumors to obtain nutrition. Herein, RPV-modified epirubicin and dioscin co-delivery liposomes were successfully prepared. These liposomes showed ideal physicochemical properties, enhanced tumor targeting and accumulation in tumor sites, and inhibited VM channel formation, tumor angiogenesis, migration and invasion. The liposomes also downregulated VM-related and angiogenesis-related proteins in vitro. Furthermore, when tested in vivo, the targeted co-delivery liposomes increased selective accumulation of drugs in tumor sites and showed extended stability in blood circulation. In conclusion, RPV-modified epirubicin and dioscin co-delivery liposomes showed strong antitumor efficacy in vivo and could thus be considered a promising strategy for NSCLC treatment. K E Y W O R D Sangiogenesis, cell-penetrating peptide, co-delivery liposome, non-small cell lung cancer, vasculogenic mimicry

<p>Tumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC</p>

“…MMP2-responsive liposomes were prepared using thinfilm hydration according to a previous method. 19 In short, EPC, Chol, DSPE-PEG 2000 , DSPE-PEG 2000 -CPP-PVGLI-PEG 5000 , and dioscin were dissolved in methyl alcohol at a molar ratio of 100:30:1:1:5 in a pear-shaped bottle, dried by rotary evaporator at 37°C to obtain a thin film, and the thin film was hydrated with 5 mL ammonium sulfate by sonication in a water bath. The suspensions were then sonicated in an ice bath with a probe sonicator for 10 minutes at 200 W. Subsequently, the samples were extruded through the polycarbonate membranes for 3 times with 200 nm pores.…”

“…Finally, the cellular uptake and distribution were analyzed by a fluorescence confocal microscope (Nikon Cl-si TE2000, Tokyo, Japan). 19,23 Destructing Effects in A549 Cells Spheroids…”

“…38 Our previous research results also showed that the dioscin as a regulator encapsulated in liposomes can play an ideal anti-tumor effect, which is manifested as inhibition of tumor cell invasion and migration, antiangiogenesis and VM formation. 19,23 Based on the above, we chose dioscin as a regulator, encapsulated inside the liposomes, and played a helpful anti-tumor effect in this study. Our results also indicated that the addition of dioscin could significantly inhibit the tumor cells' invasion and migration.…”

Nrf2 Down-Regulation by Camptothecin Favors Inhibiting Invasion, Metastasis and Angiogenesis in Hepatocellular Carcinoma

“…However, EPI treatment induced Nrf2 expression and inhibited the proliferation of Huh7 cells as well as the tumor growth of Huh7 and H22. It might be due to that EPI could induce other inhibition patterns of cell growth, such as pro-apoptosis, G2/M arrest by CDK1 down-regulation, as well as the limitation of the nutrition supply towards cancer cells (52)(53)(54). After down-regulating the EPI-induced Nrf2 by CPT, the proliferation and tumor growth of HCC were obviously decreased.…”

In vivo gene delivery mediated by non-viral vectors for cancer therapy

“…There are several other non-viral vectors used for the delivery of various nucleic acid materials for lung cancer [166][167][168][169][170][171][172][173]. Another most common genetic alteration happen in the lung cancer is associated with the tumor suppressor genes.…”