Hyaluronic Acid-Based Nanocarriers for Anticancer Drug Delivery

Abstract

Hyaluronic acid (HA), a main component of the extracellular matrix, is widely utilized to deliver anticancer drugs due to its biocompatibility, biodegradability, non-toxicity, non-immunogenicity and numerous modification sites, such as carboxyl and hydroxyl groups. Moreover, HA serves as a natural ligand for tumor-targeted drug delivery systems, as it contains the endocytic HA receptor, CD44, which is overexpressed in many cancer cells. Therefore, HA-based nanocarriers have been developed to improve drug delivery efficiency and distinguish between healthy and cancerous tissues, resulting in reduced residual toxicity and off-target accumulation. This article comprehensively reviews the fabrication of anticancer drug nanocarriers based on HA in the context of prodrugs, organic carrier materials (micelles, liposomes, nanoparticles, microbubbles and hydrogels) and inorganic composite nanocarriers (gold nanoparticles, quantum dots, carbon nanotubes and silicon dioxide). Additionally, the progress achieved in the design and optimization of these nanocarriers and their effects on cancer therapy are discussed. Finally, the review provides a summary of the perspectives, the lessons learned so far and the outlook towards further developments in this field.

In situ administration of STING-activating hyaluronic acid conjugate primes anti-glioblastoma immune response

“…7 ) [ 12 , 33 ]. We sought to address this challenge by conjugating MSA2 to HA, ameliorating its solubility profile and cell uptake as previously demonstrated with other drugs [ 59 , 60 ]. Compared to our previous approaches [ 53 , 61 ], the advantages reside in a simultaneous trigger of both innate and adaptive immunity with a single immunotherapeutic agent after an intracranial injection.…”

Synthesis of a smart pH sensitive micelle containing hyaluronic acid-curcumin bioconjugate against colorectal cancer

“…Thus the drug-polymer conjugate can reach tumors at high concentrations. Moreover, the biocompatibility of the HA as a biodegradable biopolymer allows for multiple injections of the systems for better therapeutic outcomes [41][42][43].…”

CD44 in Bladder Cancer

“…There are several therapeutics being developed that take advantage of CD44 protein levels commonly being higher in bladder cancer compared to normal urothelium and that CD44 is a receptor for HA [ 81 ] ( Table 2 ). A promising approach involves the attachment of HA molecules to gold (Au)-augmented silicon dioxide (SiO 2 ) particles.…”

“…Approaches include local resection or administering therapeutics directly into the lumen of the bladder with a catheter. Given the biologically relevant physiochemical properties of HA polymers to mimic the extracellular matrix and form organic carrier molecules (e.g., liposomes and nanoparticles), they can be engineered into hydrogels and enriched with specific cargos [ 81 ]. Additionally, given the sticky nature of hydrogels, they also increase the residency time of any treatment when they are administered to the bladder lumen at the same time as a chemotherapeutic agent in intravesical delivery.…”