Hyaluronic Acid-Based Nanocarriers for Targeted Cancer Therapy
Summary
Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan widely distributed in the extracellular matrix. Its high biocompatibility, biodegradability and non-immunogenicity, combined with a strong affinity for receptors overexpressed on tumour cells—most notably CD44—make it an ideal ligand for targeted delivery. By conjugating or coating nanoscale drug carriers with HA, researchers have developed micelles, liposomes, polymeric nanoparticles and hydrogels that exploit both passive tumour accumulation (via the enhanced permeability and retention effect) and active receptor-mediated endocytosis. Engineered HA nanocarriers can encapsulate chemotherapeutic agents, small interfering RNAs (siRNAs) and imaging probes, offering controlled drug release in response to pH, enzymatic degradation or redox conditions within the tumour microenvironment. This versatility has yielded platforms capable of overcoming multidrug resistance, reducing off-target toxicity and integrating diagnostic functionality for real-time treatment monitoring.
Research from Nature Portfolio
Recent studies have demonstrated that HA-functionalised poly(ethyleneimine)/poly(ethylene glycol) nanoparticles can deliver MDR1-targeting siRNA to CD44-overexpressing ovarian cancer cells, effectively downregulating P-glycoprotein expression and sensitising tumours to paclitaxel. In murine models, sequential administration of these HA-based siRNA carriers followed by chemotherapy suppressed tumour growth more robustly than either treatment alone, highlighting the potential of HA nanocarriers to circumvent acquired drug resistance.
Hyaluronic Acid-Based Nanocarriers for Targeted Cancer Therapy publication trend
The graph below shows the total number of articles in hyaluronic acid-based nanocarriers for targeted cancer therapy across all publications each year (not limited to Nature Index journals).
Technical terms
Hyaluronic acid (HA): Linear anionic polysaccharide that binds specific cell-surface receptors and is widely used for biocompatible drug delivery.
CD44 receptor: Transmembrane glycoprotein overexpressed on many tumour cells; mediates HA-dependent endocytosis of nanocarriers.
Nanocarrier: Nanoscale vehicle—such as a micelle, liposome or polymeric nanoparticle—designed to encapsulate and transport therapeutic or diagnostic agents.
siRNA: Short interfering RNA molecule that mediates sequence-specific gene silencing by degrading target mRNA.
Theranostic: Combined therapeutic and diagnostic approach, often integrating drug delivery with imaging capabilities.
EPR effect: Enhanced permeability and retention phenomenon whereby nanosized particles preferentially accumulate in tumour tissue due to leaky vasculature and poor lymphatic drainage.
References
- Hyaluronic Acid-Based Nanomaterials for Cancer Therapy. Polymers (2018).
- MDR1 siRNA loaded hyaluronic acid-based CD44 targeted nanoparticle systems circumvent paclitaxel resistance in ovarian cancer. Scientific Reports (2015).
- Hyaluronic acid-based nanoplatforms for Doxorubicin: A review of stimuli-responsive carriers, co-delivery and resistance suppression. Carbohydrate Polymers (2021).
- Hyaluronic Acid-Based Theranostic Nanomedicines for Targeted Cancer Therapy. Cancers (2020).
- Hyaluronic Acid-Coated Nanomedicine for Targeted Cancer Therapy. Pharmaceutics (2019).
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