Post cross-linked ROS-responsive poly(ß-amino ester)-plasmid polyplex NPs for gene therapy of EBV-associated nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most common tumors in South China and Southeast Asia and is thought to be associated with Epstein-Barr virus (EBV) infection. Downregulation of latent membrane protein 1 (LMP1) encoded by EBV can reduce the expression of NF-κB and PI3K, induce apoptosis, and inhibit the growth of EBV-related NPC. For targeted cleavage of the Lmp1 oncogene via the CRISPR/Cas9 gene editing system, a post cross-linked ROS-responsive poly(ß-amino ester) (PBAE) polymeric vector was developed for the delivery of CRISPR/Cas9 plasmids both in vitro and in vivo. After composition optimization, the resultant polymer-plasmid polyplex nanoparticles (NPs) showed a diameter of ∼230 nm and a zeta potential of 22.3 mV with good stability. Compared with the non-cross-linked system, the cross-linked NPs exhibited efficient and quick cell uptake, higher transfection efficiency in EBV-positive C666-1 cells (53.5% vs. 40.6%), more efficient gene editing ability against the Mucin2 model gene (Muc2) (17.9% vs. 15.4%) and Lmp1 (8.5% vs. 5.6%), and lower intracellular reactive oxygen species (ROS) levels. The NPs achieved good tumor penetration and tumor growth inhibition in the C666-1 xenograft tumor model via Lmp1 cleavage, indicating their potential for gene therapy of EBV-related NPC.

Enhanced photodynamic therapy/photothermo therapy for nasopharyngeal carcinoma via a tumour microenvironment-responsive self-oxygenated drug delivery system.

The hypoxic nature of tumours limits the efficiency of oxygen-dependent photodynamic therapy (PDT). Hence, in this study, indocyanine green (ICG)-loaded lipid-coated zinc peroxide (ZnO2) nanoparticles (ZnO2@Lip-ICG) was constructed to realize tumour microenvironment (TME)-responsive self-oxygen supply. Near infrared light irradiation (808 nm), the lipid outer layer of ICG acquires sufficient energy to produce heat, thereby elevating the localised temperature, which results in accelerated ZnO2 release and apoptosis of tumour cells. The ZnO2 rapidly generates O2 in the TME (pH 6.5), which alleviates tumour hypoxia and then enhances the PDT effect of ICG. These results demonstrate that ZnO2@Lip-ICG NPs display good oxygen self-supported properties and outstanding PDT/PTT characteristics, and thus, achieve good tumour proliferation suppression.

Oxymatrine loaded nitric oxide-releasing liposomes for the treatment of ulcerative colitis.

Oxymatrine (OM) is the biologically active ingredient of Chinese medicinal herb Sophora flavescens, which is reported to be effective on alleviating ulcerative colitis (UC) due to its anti-inflammatory property. However, its highly effective dose is an obstacles to its application. Therefore, liposome was used to encapsulate OM, realize targeting delivery to colitis and thus reduce drug dosage. Meanwhile, considering the potential anti-inflammatory ability of nitric oxide (NO), a NO donor, d-α-tocopheryl polyethylene glycol succinate nitrate (TN), was introduced into the liposomal system and OM loaded NO-releasing liposomes (OM@TN-lip) were prepared in order to co-deliver OM and NO to the inflammatory lesions of DSS-induced UC mice to achieve the combination therapy. OM@TN-lip was multilamelar sphere with the encapsulation efficiency of ~70%, the diameter of ~200 nm and ζ-potential of about -13 mV. Bio-distribution results revealed the liposomes could efficiently accumulate in the inflammatory colon by diffusion and maintain for more than 36 h. In UC mice model, OM@TN-lip showed significant alleviation of inflammation and the treatment was highly related to down-regulation of pro-inflammatory cytokines TNF-α, IFN-γ, IL-1ß and IL-6, decrease of macrophages infiltration, activity decrease of myeloperoxidase (MPO) and cyclooxygenase-2 (COX-2), and rebuilding antioxidant/oxidation balance by reducing reactive oxygen species (ROS) and increasing Glutathione (GSH) in colon.