Abstract
Poly(sialic acid) (PSA) is a natural hydrophilic biodegradable and non-immunogenic biopolymer, receptors for its monomer are expressed on peripheral blood neutrophils (PBNs), which plays important roles in the progression and invasion of tumors. A poly(sialic acid)–octadecylamine conjugate (PSA–ODA) was synthesized and then anchor it on the surface of liposomal pixantrone (Pix-PSL), to achieve an improved anticancer effect. The liposomes were prepared using a remote loading method via a pH gradient, and then assessed for particle size, zeta potential encapsulation efficiency, in vitro release, and in vitro cytotoxicity. Simultaneously, in vitro and in vivo cellular uptake studies confirmed that PSA-decorated liposomes provided an enhanced accumulation of liposomes in PBNs. An in vivo study presented that the anti-tumor activity of Pix-PSL was superior to that of other Pix formulations, probably due to the efficient targeting of PBNs by Pix-PSL, after which PBN containing Pix-PSL (Pix-PSL/PBNs) in the blood circulation are recruited by the tumor microenvironment. These findings suggest that PSA-decorated liposomal Pix may provide a neutrophil-mediated drug delivery system (DDS) for the eradication of tumors, which represents a promising approach for the tumor targeting of chemotherapeutic treatments.
Highlights
The relatively poor results of nonspecific chemotherapy for solid tumors promoted studies to identify new treatment strategies (Wang et al, 2011)
The NMR peaks for the Poly(sialic acid) (PSA)–ODA were consistent with previous reports: 1.90 ppm (s, CH3–CO, PSA), 1.25–1.35 ppm (m, –CH2, ODA) and 0.88 ppm (t, –CH3, ODA)
The spectra of poly(sialic acid)–octadecylamine conjugate (PSA–ODA) showed: a peak at 1738 cm–1, attributed to C@O stretching of the carbamate linkage (–OCO–NH–); peaks at 2852 and 2919 cm–1, attributed to C–H stretching of ODA; and, a peak at 1638 cm–1, attributed to C@O stretching of the carboxylic groups of PSA
Summary
The relatively poor results of nonspecific chemotherapy for solid tumors promoted studies to identify new treatment strategies (Wang et al, 2011). It has been reported that neutrophils will be recruited to tumor sites via signals produced by cells of the tumor microenvironment, including chemokine (Viola et al, 2012; Raccosta et al, 2013), cytokines (Fossati et al, 1999; Moore et al, 1999; Benevides et al, 2015; Coffelt et al, 2015), and hydrogen peroxide (Feng et al, 2006) These cells are recognized as tumorassociated neutrophils (TANs), which can remodel the extracellular matrix (ECM) in the tumor microenvironment (Dumitru et al, 2013), or act directly on tumor cells to enhance tumor proliferation and invasion (Coussens et al, 2000; Wislez et al, 2003). The results showed that PSA-modified liposomes can target neutrophils efficiently and neutrophil-mediated DDS is a promising approach for tumor-targeting treatment
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