Targeted delivery of pixantrone to neutrophils by poly(sialic acid)-p-octadecylamine conjugate modified liposomes with improved antitumor activity.
Based on the knowledge that poly(sialic acid) is a critical element for tumour development and that the receptors for its monomer are expressed on neutrophils, which play important roles in the progression and invasion of tumours, a poly(sialic acid)-p-octadecylamine conjugate (PSA-p-ODA) was synthesised and used to modify the surface of liposomal pixantrone (Pix-PSL) to improve the delivery of Pix to peripheral blood neutrophils (PBNs). The liposomes were fabricated using a remote loading technology via a pH gradient, and were then assessed for particle size, encapsulation efficiency, in vitro release, in vitro cytotoxicity, and pharmacokinetics. Simultaneously, in vitro and in vivo cellular uptake studies demonstrated that Pix-PSL provided an enhanced accumulation of Pix in PBNs. An in vivo study showed that the anti-tumour activity of Pix-PSL was superior to that of other formulations, probably owing to the efficient targeting of PBNs by Pix-PSL, after which PBNs containing Pix-PSL (Pix-PSL/PBNs) in the circulatory system are recruited by the tumour microenvironment. These findings suggest that PSA-p-ODA-decorated liposomal Pix may provide a neutrophil-mediated drug delivery system (DDS) for the eradication of tumours, and thus represents a promising approach for the tumour targeting of chemotherapeutic treatments.
['Luo|Xiang|X|', 'Liu|Mingqi|M|', 'Hu|Ling|L|', 'Qiu|Qiujun|Q|', 'Liu|Xinrong|X|', 'Li|Cong|C|', 'Lu|Mei|M|', 'Liu|Yang|Y|', 'Zhang|Ting|T|', 'Zhou|Songlei|S|', 'McClements|David Julian|DJ|', 'Jia|Xian|X|', 'Deng|Yihui|Y|', 'Song|Yanzhi|Y|']
D000588:Amines D000818:Animals D000970:Antineoplastic Agents D045744:Cell Line, Tumor D002626:Chemistry, Pharmaceutical D004337:Drug Carriers D016503:Drug Delivery Systems D007546:Isoquinolines D008081:Liposomes D008297:Male D051379:Mice D019158:N-Acetylneuraminic Acid D009504:Neutrophils D010316:Particle Size D051381:Rats D017208:Rats, Wistar D012510:Sarcoma 180 D059016:Tumor Microenvironment D023041:Xenograft Model Antitumor Assays
Liposomes Poly(sialic acid) Peripheral blood neutrophils Drug delivery system Tumour-targeting