Abstract
For enhanced intracellular accumulation of 6-mercaptopurine (6-MP) in leukemia, a folate receptor-targeted and glutathione (GSH)-responsive polymeric prodrug nanoparticle was made. The nanoparticles were prepared by conjugating 6-MP to carboxymethyl chitosan via a GSH-sensitive carbonyl vinyl sulfide linkage, ultrasonic self-assembly and surface decoration with folate. The TEM graphs shows that the as-synthesized nanoparticles are spherical with a particle size of 170~220 nm. In vitro drug release of nanoparticles demonstrated acceptable stability in PBS containing 20 μM GSH at pH 7.4. However, the cumulative drug release rate of the samples containing 20 mM and 10 mM GSH medium reached 78.9% and 64.8%, respectively, in pH 5.0 at 20 h. This indicated that this nano-sized system is highly sensitive to GSH. The inhibition ratio of folate-modified nanoparticles compared to unmodified nanoparticles was higher in cancer cells (human promyelocytic leukemia cells, HL-60) while their cytotoxicity was lower in normal cells (mouse fibroblast cell lines, L929). Furthermore, in vitro cancer cell incubation studies confirmed that folate-modified nanoparticles therapeutics were significantly more effective than unmodified nanoparticles therapeutics. Our results suggest that folate receptor-targeting and GSH-stimulation can significantly elevate tumour intracellular drug release. Therefore, folate-modified nanoparticles containing chemoradiotherapy is a potential treatment for leukemia therapy.
Highlights
Over the past few years, chemotherapy has become the most accepted treatment of malignancy. antitumor drugs have the ability to inhibit the proliferation of cancer cells, the free spread of these small molecules to normal organs may result in serious systematic toxicity after long-term usage [1,2,3,4]
Glutathione (GSH)-sensitive polymeric nanoparticles for tumour-targeted delivery of anticancer drugs have attracted more and more attention in recent years due to several advantages, such as improving the stability and solubility of drugs, avoiding premature leaking in the blood stream and selective drug release enhancement in target tissues or cells, and increasing the circulation time in the physiological environment etc. [8,9]
The results presented the mass content of 18% for folate and confirmed the nanoparticles’ stability
Summary
Antitumor drugs have the ability to inhibit the proliferation of cancer cells, the free spread of these small molecules to normal organs may result in serious systematic toxicity after long-term usage [1,2,3,4]. Mar. Drugs 2018, 16, 439; doi:10.3390/md16110439 www.mdpi.com/journal/marinedrugs. Mar. Drugs 2018, 16, 439 anticancer drugs [5,6,7]. Glutathione (GSH)-sensitive polymeric nanoparticles for tumour-targeted delivery of anticancer drugs have attracted more and more attention in recent years due to several advantages, such as improving the stability and solubility of drugs, avoiding premature leaking in the blood stream and selective drug release enhancement in target tissues or cells, and increasing the circulation time in the physiological environment etc. Glutathione (GSH)-sensitive polymeric nanoparticles for tumour-targeted delivery of anticancer drugs have attracted more and more attention in recent years due to several advantages, such as improving the stability and solubility of drugs, avoiding premature leaking in the blood stream and selective drug release enhancement in target tissues or cells, and increasing the circulation time in the physiological environment etc. [8,9]
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