Protein liposomes-mediated targeted acetylcholinesterase gene delivery for effective liver cancer therapy

Abstract

Background Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy. Results Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration. Conclusions This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.

Understanding Nanomaterial–Liver Interactions to Facilitate the Development of Safer Nanoapplications

“…related to liver fibrosis and cirrhosis can also be targeted by LNPs. [65,112,221,222] For example, the larger LNPs that cannot penetrate through the fenestrae could be delivered to LSECs and induce the target gene silencing. Furthermore, the size and composition of LNPs were important for endothelium-specific delivery.…”

Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis

“…Transferrin is an endogenous protein that ferries Fe 3+ to cells overexpressing the transferrin receptor [ 38 ]. As HCC cells have abnormal iron metabolism, they overexpress transferrin receptors [ 39 ]. Grafting naturally occurring transferrin onto the surfaces of Fe-HMON NPs via polyethylene glycol (PEG) creates a target ligand (Fe-HMON-Tf NPs), thereby reducing phagocytosis in the reticuloendothelial system, retaining high solid tumour permeability and retention effects, and enhancing specific nanoplatform targeting [ 40 ].…”

Magnetofection In Vivo by Nanomagnetic Carriers Systemically Administered into the Bloodstream

“…That causes rapid plasma clearance of the nanocarriers leading to short nanoparticle plasma half-life [102]. Therefore, it is necessary to study in detail the issues related to the factors that affect blood circulation [8,103], as well as elimination [104,105] of nanoparticles for successful applications of in vivo magnetofection, search for new hybrid delivering nanomaterials [106][107][108][109] or implementation of more efficient biochemical binding and targeting techniques [110][111][112][113][114][115][116]. However, we believe that the magnetofection technique can become a solid option for in vivo targeting combined with improved efficacy of gene delivery, potentially in combination with other physical techniques (electroporation, sonoporation) if appropriate magnetic fields can be generated and if an ideal coating of magnetic particles is found.…”