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Published on: June 23, 2020
Natural polysaccharide-incorporated hydroxyapatite as size-changeable, nuclear-targeted nanocarrier for efficient
Xiaoxiang Ren1, Zeng Yi2, Zhe Sun2
1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China. xli20004@yahoo.com and Department of Biomedical Engineering, University of Groningen, Antonius Deusinglaan 1, 9713 Groningen, The Netherlands.
Abstract:
Targeted delivery of anticancer drugs is one of the most promising methods for cancer therapy. However, barriers including complicated procedures, costly preparation, and toxic side effects have restricted the development of nuclear-targeted nanocarriers. Natural polysaccharides as extracellular matrix constituents or analogs play an important role in biomineralization. Herein, a simple, polysaccharide-intervened preparation of hydroxyapatite (HA) hybrid nanoparticles (NPs) with low crystallinity was used as a bio-safe carrier for targeting the delivery of doxorubicin (DOX) for efficient anticancer therapy. The poorly crystallized hybrid HA NPs were specifically taken up by cancer cells (HeLa cells), and subsequently, the abrupt degradation of HA nanoparticles would cause a change in the osmotic pressure, leading to the explosive death of cancer cells. Furthermore, the hybrid HA NPs were size changeable and capable of directly delivering the anti-cancer drug into the nucleus of cancer cells, thereby efficiently killing cancer cells. In addition, the HA/ALG NPs reduce the toxicity of DOX to L929 cells and cause little negative effect on normal tissue cells. The in vitro and in vivo experiments confirmed that the size-changeable HA-ALG/DOX could be a promising nuclear-targeted delivery nanocarrier for efficient cancer therapy.
Insights
Researchers developed a novel hydroxyapatite (HA) nanoparticle carrier using natural polysaccharides. This bio-safe carrier effectively targets cancer cells, delivering doxorubicin (DOX) to the nucleus for enhanced anticancer therapy with reduced toxicity.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
Background:
- Targeted drug delivery aims to improve cancer therapy efficacy.
- Barriers to nuclear-targeted nanocarriers include complexity, cost, and toxicity.
- Natural polysaccharides are key in biomineralization and can be used in nanocarrier development.
Purpose of the Study:
- To develop a simple, bio-safe, and effective nanocarrier for targeted anticancer drug delivery.
- To utilize polysaccharide-intervened hydroxyapatite (HA) hybrid nanoparticles (NPs) for doxorubicin (DOX) delivery.
- To investigate the potential of these NPs for nuclear targeting and enhanced cancer cell death.
Main Methods:
- A simple, polysaccharide-intervened preparation of low-crystallinity hydroxyapatite (HA) hybrid nanoparticles (NPs).
- Utilized HA NPs as a bio-safe carrier for doxorubicin (DOX) delivery.
- Evaluated cellular uptake by cancer cells (HeLa) and drug release mechanisms.
- Assessed nanoparticle degradation, osmotic pressure changes, and subsequent cancer cell death.
- Investigated size-changeable properties for direct nuclear delivery of DOX.
- Tested toxicity on normal cells (L929) and evaluated in vitro and in vivo efficacy.
Main Results:
- The poorly crystallized HA NPs were specifically internalized by cancer cells.
- Degradation of HA NPs induced osmotic pressure changes, leading to cancer cell death.
- The hybrid HA NPs demonstrated size-changeable properties for direct nuclear drug delivery.
- HA/ALG NPs reduced doxorubicin toxicity to normal cells (L929) with minimal negative effects.
- In vitro and in vivo experiments confirmed the efficacy of HA-ALG/DOX as a nuclear-targeted delivery system.
Conclusions:
- Polysaccharide-intervened HA hybrid nanoparticles offer a simple and bio-safe approach for targeted cancer therapy.
- These nanoparticles effectively deliver doxorubicin to the nucleus of cancer cells, inducing cell death.
- The developed nanocarrier system shows reduced toxicity to normal tissues, highlighting its therapeutic potential.
