Abstract
Although self-assembled nanoparticles (SNPs) have been used extensively for targeted drug delivery, their clinical applications have been limited since most of the drugs are released into the blood before they reach their target site. In this study, metal-phenolic network (MPN)-coated SNPs (MPN-SNPs), which consist of an amphiphilic hyaluronic acid derivative, were prepared to be a pH-responsive nanocarrier to facilitate drug release in tumor microenvironments (TME). Due to their amphiphilic nature, SNPs were capable of encapsulating doxorubicin (DOX), chosen as the model anticancer drug. Tannic acid and FeCl3 were added to the surface of the DOX-SNPs, which allowed them to be readily coated with MPNs as the diffusion barrier. The pH-sensitive MPN corona allowed for a rapid release of DOX and effective cellular SNP uptake in the mildly acidic condition (pH 6.5) mimicking TME, to which the hyaluronic acid was exposed to facilitate receptor-mediated endocytosis. The DOX-loaded MPN-SNPs exhibited a higher cytotoxicity for the cancer cells, suggesting their potential use as a drug carrier in targeted cancer therapy.
Highlights
Nanomedicine, an offshoot of nanotechnology, has been studied extensively for use in biomedical applications including targeted therapy and precise diagnosis of intractable diseases [1,2,3,4,5]
In an attempt to develop the carrier of hydrophobic anticancer drugs for targeted cancer therapy, we have prepared metal-phenolic network (MPN)-HA nanoparticles (HANPs) which can release the drugs by recognizing the mildly acidic tumor microenvironments (TME)
We explored the potential of MPN as an effective diffusion barrier on the HANPs for pH-responsive delivery of hydrophobic anticancer drugs
Summary
Nanomedicine, an offshoot of nanotechnology, has been studied extensively for use in biomedical applications including targeted therapy and precise diagnosis of intractable diseases [1,2,3,4,5]. Several formulations are currently on the market or in clinical trials for cancer therapy, including Genexol® PM (paclitaxel-encapsulated polymeric micelle) and SP1049C (doxorubicin-encapsulated polymeric micelle) [6,7,8] These formulations exhibit superior therapeutic effects and reduced side effects, primarily ascribed to their unique properties, which improve the hydrophobic drug’s water solubility and/or enhance the drug’s accumulation at the tumor site by the enhanced permeation and retention effect [9]. Stimuli-responsive polymers have emerged as drug carriers for cancer therapy since they can be designed to release the anticancer drugs in response to tumor-specific microenvironments (TMEs) such as a low pH, abnormal levels of reactive oxygen species, and hypoxic conditions [12,13,14,15]. There are concerns about the toxicity of fragments generated by cleaving stimuli-responsive linkers or moieties in nanomedicines [18,19]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
