Abstract
Biodegradable nanoparticles and micelles are promising nanosystems for the targeted delivery of potent anticancer drugs. By using specialized polymers as nanocarriers, targeted drug delivery and release can be developed. We developed thiol-hyaluronic acid (HA-SH)/chitosan (CS) nanoparticles with redox/pH dual-responsiveness via electrostatic self-assembly followed by spontaneous chemical cross-linking. The nanoparticle surface charges were reversible through different HA-SH and CS mass ratios. Doxorubicin (DOX) was used as a model drug. Dual cross-linked nanoparticles with diameters of approximately 300 nm exhibited superior stability under physiological conditions compared with nanoparticles without disulfide cross-linking. DOX was loaded more efficiently into negative nanoparticles (45.7 wt%) than positive nanoparticles (14.2 wt%). Drug release from negative nanoparticles (ζ potential of approximately −20) was higher (87.8 wt%) at pH 4.5 and in the presence of 10 mM glutathione. Positive nanoparticles (ζ potential of approximately +20) showed the same trend, but the release rate was slower than that of negative nanoparticles. DOX-loaded HA-SH/CS particles were taken up by human breast cancer cells (SKBR3), and the loaded drug was released, exhibiting potential antitumor efficacy. The HA-SH/CS nanoparticles in this study were stable under physiological conditions and are promising candidates for the targeted delivery and release of anticancer drugs.
Highlights
Biodegradable nanoparticles and micelles have emerged as one of the most promising nanosystems for the controlled and targeted delivery of potent anticancer drugs. They allow for responding to specific microenvironmental changes of cancer cells and quick drug release, which are highly desired functions in cancer treatments with minimal undesired effects on normal cells [1,2,3,4,5,6]
Hyaluronic acid (HA), or hyaluronan, is a linear polysaccharide that consists of alternating units of repeating disaccharide, β-1,4-D-glucuronic acid–β-1,3-N-acetyl-Dglucosamine
It was hypothesized that DOX-loaded HA-SH/CS nanoparticles, with their polyelectrolyte complexes and disulfide cross-linking, would be stable under physiological conditions, preferentially accumulate at the target site, and release their payload in the acid-cleavable and glutathione-reducing microenvironments of cancer cells
Summary
Biodegradable nanoparticles and micelles have emerged as one of the most promising nanosystems for the controlled and targeted delivery of potent anticancer drugs. They allow for responding to specific microenvironmental changes of cancer cells and quick drug release, which are highly desired functions in cancer treatments with minimal undesired effects on normal cells [1,2,3,4,5,6]. It was hypothesized that DOX-loaded HA-SH/CS nanoparticles, with their polyelectrolyte complexes and disulfide cross-linking, would be stable under physiological conditions, preferentially accumulate at the target site, and release their payload in the acid-cleavable and glutathione-reducing microenvironments of cancer cells.
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