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A photo-controlled hyaluronan-based drug delivery nanosystem for cancer T therapy
Feifei Sun1, Peng Zhang1, Yinyin Liu, Chunbo Lu, Yuanhao Qiu, Haibo Mu, Jinyou Duan
College of Chemistry & Pharmacy, Shaanxi Key Laboratory of Natural Products & Chemical Biology, Northwest A&F University, Yangling 712100, Shaanxi, China
In this paper, a novel photo-controlled drug-loaded nanomicelles were self-assembled by the amphiphile of hyaluronan-o-nitrobenzyl-stearyl chain (HA-NB-SC) with doxorubicin (DOX) encapsulated within the hydro-phobic core. DOX-loaded HA-NB-SC nanomicelles are ∼139 nm in diameter. CD44-overexpressed HeLa Dorsomorphin (Compound C) can easily take up HA-NB-SC micelles through recognition of HA moiety. DOX-loaded HA-NB-SC nanomicelles could be disassembled upon UV light (365 nm) and consequently, release DOX at desired pathological sites. Furtherly, nitrosobenzaldehyde derivative, photo-induced products of HA-NB-SC and DOX could inhibit the proliferation of HeLa cells together. This strategy may shed some light on delivery of hydrophobic anti-cancer drugs in a con-trolled manner.
Hyaluronan (HA), also referred to hyaluronic acid or hyaluronate, a naturally linear polysaccharide, is composed of repeated units of β-4 linked D-glucuronic acid and β-3 linked N-acetyl-D-glucosamine (Weissmann & Meyer, 1954; Weissmann, Meyer, Sampson, & Linker, 1954). HA is a polyanionic polysaccharide with low toxicity distributed widely in extracellular matrix and connective tissues. In recent years, HA has been widely explored for the development of anticancer therapies owing to its outstanding biocompatibility and biodegradable property. What's more, HA is a ligand for CD44 receptors, which are overexpressed in a variety of tumor types (Choi et al., 2011; Jin et al., 2012; Prestwich, 2011). HA has some functional groups including carboxyl and hydroxyl groups, which aﬀord a space for chemical structural modification. For example, there is a nanocarrier based on HA for dual targeting and synergistic eﬀects of photothermal and che-motherapy, in which HA conjugated with triphenylphosphonium (TPP) and boronic acid (BA) diol-linked β-cyclodextrin (β-CD) forms an in-clusion complex with paclitaxel (PTX) (Kim, In, & Park, 2017). Based on these reasons, some hydrophobic agents, such as ceramide (Cho et al., 2011) and 5β-cholanic acids (Choi et al., 2009), have been conjugated to HA to gain targeting nanomicelles for anticancer drug delivery to boost cellular uptake via CD44-mediated endocytosis. r> Chemotherapy is still considered as the most critical strategy to treat cancer. However, traditional chemotherapy still undergoes many
E-mail address: [email protected] (J. Duan).