Abstract
Nanoparticles (NPs) have demonstrated a potential for hepatocarcinoma therapy. However, the effective and safe NP-mediated drug transportation is still challenging due to premature leakage and inaccurate release of the drug. Herein, we designed a series of core cross-linking galactose-based glycopolymer-drug conjugates (GPDs) NPs with both redox-responsive and pH-sensitive characteristics to target and program drug release. Glycopolymer is comprised of galactose-containing units, which gather on the surface of GPD NPs and exhibit specific recognition to hepatocarcinoma cells, which over-express the asialoglycoprotein receptor. GPD NPs are stable in a normal physiological environment and can rapidly release the drug in hepatocarcinoma cells, which are reductive and acidic, by combining disulfide bond cross-linked core, as well as boronate ester-linked hydrophilic glycopolymer chain and the hydrophobic drug.
Highlights
Human hepatocellular carcinoma (HCC) is a common type of primary liver cancer and is diagnosed in more than half a million people worldwide (de Souza et al, 2015)
Their molecular weights were relatively higher than that of GPD1 and GPD2. These glycopolymer-drug conjugates (GPDs) exhibited amphiphilic characteristic because galactose is hydrophilic, while DOX moieties show hydrophobic nature. These results demonstrated the hydrophilic/hydrophobic balance of the designed GPDs can be adjusted by varying the molar ratio of three units, which regulated the self-assembly behavior of GPDs to some extent
The mean fluorescent intensity (MFI) value in HepG2 cells was increased with time and became nearly twofold when compared with that in COS7 and MGC-803 cells after 4 h. These results indicated that GPD3 NPs can selectively transport DOX to HepG2 cells and cause efficient cell inhibition. We hypothesized that this difference was due to the specific recognition between galactose, which coated on the surface of GPD NPs, and ASGPR exposed on HepG2 cells, thereby resulting in ASGPR-mediated internalization
Summary
Human hepatocellular carcinoma (HCC) is a common type of primary liver cancer and is diagnosed in more than half a million people worldwide (de Souza et al, 2015). Chemotherapy is a common HCC treatment strategy that is limited because it is always accompanied by doselimiting toxicity, high rate of tumor recurrence, and drug resistance (Dutta and Mahato, 2017; Kuruvilla et al, 2017). Nanotechnology is applied to address these problems and has obtained effective molecular-level diagnosis (Mura et al, 2013; Lim et al, 2015). It serves as vectors, sensors, and targeting agents to achieve optimal efficacy in precise drug transportation because of its potential to alter the biodistribution and pharmacokinetics of drugs (Tao et al, 2013, 2015, 2016; Li et al, 2016; Zhang et al, 2017; Dai et al, 2018). The clinical application of the nanoparticle (NP)-mediated treatment is still challenging due to the premature drug leakage and inaccurate drug release in dilute bloodstream, thereby resulting in serious systemic side-effects to normal tissues and cells (Tao et al, 2014; Tibbitt et al, 2016; Chen et al, 2017; Rosenblum et al, 2018)
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