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

Abstract

Background: Non-small cell lung cancer (NSCLC) is one of the most lethal types of cancer with highly infiltrating. Chemotherapy is far from satisfactory, vasculogenic mimicry (VM) and angiogenesis results in invasion, migration and relapse. Purpose: The objective of this study was to construct a novel CPP (mmp) modified vinorelbine and dioscin liposomes by two new functional materials, DSPE-PEG 2000-MAL and CPP-PVGLIG-PEG 5000 , to destroy VM channels, angiogenesis, EMT and inhibit invasion and migration. Methods and Results: The targeting liposomes could be enriched in tumor sites through passive targeting, and the positively charged CPP was exposed and enhanced active targeting via electrostatic adsorption after being hydrolyzed by MMP2 enzymes overexpressed in the tumor microenvironment. We found that CPP (mmp) modified vinorelbine and dioscin liposomes with the ideal physicochemical properties and exhibited enhanced cellular uptake. In vitro and in vivo results showed that CPP (mmp) modified vinorelbine and dioscin liposomes could inhibit migration and invasion of A549 cells, destroy VM channels formation and angiogenesis, and block the EMT process. Pharmacodynamic studies showed that the targeting liposomes had obvious accumulations in tumor sites and magnificent antitumor efficiency. Conclusion: CPP (mmp) modified vinorelbine plus dioscin liposomes could provide a new strategy for NSCLC.

Recent Advancements in Stimuli Responsive Drug Delivery Platforms for Active and Passive Cancer Targeting

“…The liposomes were responsive to overexpressed MMP2 (matrix-metalloprotease-2) enzymes, resulting in enhanced tumor targeting, internalization and enhanced anti-tumor efficacy both in vitro and in vivo. The reported novel liposomes may provide a potential platform regarding the antitumor treatment strategy for NSCLC [165]. Enzyme-responsive lipidbased drug delivery is useful regarding anticancer therapy, but still, many challenges need to be addressed.…”

Alternative Vascularization Mechanisms in Tumor Resistance to Therapy

“…Nanoparticle-based approaches have been proposed to target established VM, including cyclic RGD-functionalized nanoparticles [ 124 ], and liposomes incorporating chemotherapy and VM-targeting drugs [ 125 , 126 ]. The microtubule depolymerizing, vascular disrupting agents combretastatin A4 and DHPAC are another example of compounds that target already formed VM, rather than preventing it [ 127 ].…”

Dioscin: A review on pharmacological properties and therapeutic values

“…The targeting liposomes provided satisfactory antitumor activity by accumulating in tumor sites and thereby inhibiting the migration and invasion of neoplastic cells, destroying VM channels, blocking angiogenesis, and suppressing the EMT process. 161 A frequent limitation that dioscin is met within clinical use is its insolubility and instability in water. However, this drawback has been overcome with the use of dioscin liposomes as well as other feasible means of administering dioscin, such as the design of mixed micelle copolymers that can trap the phytochemical inside and be easily incorporated into a potential nanodrug-delivery system for chemotherapy.…”