Abstract
BackgroundTriple negative breast cancer (TNBC) is an aggressive tumor with extremely high mortality that results from its lack of effective therapeutic targets. As an adhesion molecule related to tumorigenesis and tumor metastasis, cluster of differentiation-44 (also known as CD44) is overexpressed in TNBC. Moreover, CD44 can be effectively targeted by a specific hyaluronic acid analog, namely, chitosan oligosaccharide (CO). In this study, a CO-coated liposome was designed, with Photochlor (HPPH) as the 660 nm light mediated photosensitizer and evofosfamide (also known as TH302) as the hypoxia-activated prodrug. The obtained liposomes can help diagnose TNBC by fluorescence imaging and produce antitumor therapy by synergetic photodynamic therapy (PDT) and chemotherapy.ResultsCompared with the nontargeted liposomes, the targeted liposomes exhibited good biocompatibility and targeting capability in vitro; in vivo, the targeted liposomes exhibited much better fluorescence imaging capability. Additionally, liposomes loaded with HPPH and TH302 showed significantly better antitumor effects than the other monotherapy groups both in vitro and in vivo.ConclusionThe impressive synergistic antitumor effects, together with the superior fluorescence imaging capability, good biocompatibility and minor side effects confers the liposomes with potential for future translational research in the diagnosis and CD44-overexpressing cancer therapy, especially TNBC.Graphic abstract
Highlights
Triple negative breast cancer (TNBC) is an aggressive tumor with extremely high mortality that results from its lack of effective therapeutic targets
We developed a Chitosan oligosaccharide (CO)-modified nanoparticle based on liposomes by encapsulating the photosensitizer HPPH and the hypoxia-activated prodrug TH302 into hydrophobic bilayers (CO-HPPH-TH302/Lipo) (Scheme 1)
HPPH-TH302/Lipo and CO-HPPHTH302/Lipo both had characteristic peaks at 331 nm and 660 nm, which were the characteristic peaks for TH302 and HPPH, suggesting that the drugs were successfully loaded; the encapsulation rates of TH302 and HPPH were 82% and 50%, respectively
Summary
Triple negative breast cancer (TNBC) is an aggressive tumor with extremely high mortality that results from its lack of effective therapeutic targets. As an adhesion molecule related to tumorigenesis and tumor metastasis, cluster of differentiation-44 ( known as CD44) is overexpressed in TNBC. CD44 can be effectively targeted by a specific hyaluronic acid analog, namely, chitosan oligosaccharide (CO). Hyaluronic acid receptor Cluster of differentiation-44 (CD44) is a kind of adhesion molecule that relates to tumorigenesis and tumor metastasis [10]. Chitosan oligosaccharide (CO), known as hyaluronic acid analog, can target breast cancer cells. Some researchers have been devoted to CO-decorated nanoparticles targeting tumors overexpressing CD44, such as TNBC [17, 18]
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