Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors

Abstract

Abstract:The main obstacles for cationic polyplexes in gene delivery are in vivo instability and low solid-tumor accumulation. Safe vectors with high transfection efficiency and in vivo tumor accumulation are therefore highly desirable. In this study, the amphiphilic block copolymer poly(n-butyl methacrylate)-b-poly(N-acryloylmorpholine) was synthesized by reversible addition-fragmentation chain-transfer (RAFT) radical polymerization. The corresponding well-defined vesicles with narrow size distribution were tailored by finely regulating the packing parameter (β) of copolymer (1/2 , β , 1). Compared with traditional "gold-standard" polycation (polyethylenimine, 25 kDa), plasmid DNA condensing efficiency, DNase I degradation protection, and cellular uptake were improved by the supramolecular nano vesicles. In addition, the plasmid DNA transferring efficiency in 10% fetal bovine serum medium was enlarged five times to that of polyethylenimine in renal tubular epithelial and human hepatocellular carcinoma cell lines. This improved in vitro transfection was mainly attributed to the densely packed bilayer. This stealth polyplex showed high serum stability via entropic repulsion, which further protected the polyplex from being destroyed during sterilization. As indicated by the IVIS ® Lumina II Imaging System (Caliper Life Sciences, Hopkinton, MA) 24 hours post-intravenous administration, intra-tumor accumulation of the stealth polyplex was clearly promoted. This study successfully circumvented the traditional dilemma of efficient gene transfection at a high nitrogen-from-polyethylenimine to phosphate-from-DNA ratio that is accompanied with site cytotoxicity and low stability. As such, these simply tailored noncytotoxic nano vesicles show significant potential for use in practical gene therapy.

Silencing of Livin inhibits tumorigenesis and metastasis via VEGF and MMPs pathway in lung cancer

“…In our work, we used lentiviral vectors encoding egFP as a dynamic fluorescent tracer but obtained a negative outcome, although we further opened skin-flap window and cut out the lungs for fluorescent imaging. one probable explanation was that the low aggregation of tumor nodules accounted for the negative results and the IVIS system was not fit for fluorescence imaging of tumors inside the mouse body (41,42), but rather the bioluminescent imaging (43). In the subcutaneous models, the reduction in tumor weight and tumor volume followed Livin gene silencing (9,21).…”

Antibody-Targeted Immunocarriers for Cancer Treatment

“…Based on the self-assembly mechanism, well-defined micelle and vesicle with surface targeting decorating were finely engineered. [98] We found that the temperature-regulated passive and mAb-tuned active dual targeting immunomicelles significantly enhanced intratumor accumulation and cellular uptake. The nanostructure and the dimension were also tailored to match the large endothelial cells gaps in tumors with enhanced permeability and retention (EPR).…”

A Redox-Sensitive Micelle-Like Nanoparticle Self-Assembled from Amphiphilic Adriamycin-Human Serum Albumin Conjugates for Tumor Targeted Therapy

“…Noted here, the mice with FITC administration at 0 hour were used as control. The in vivo images were observed with IVIS imaging system (excitation 500 nm) and recorded by a built-in CCD camera [ 31 ]. For further checking the tumor accumulation, the slides of the HSA/ADR and HSA-ADR NPS groups were anaesthetized by 1.5% isoflurane in 1 : 2 O 2 /N 2 .…”