3.4.3. Inorganic Hyaluronic Acid-Based Nanoparticles

Another category of HA-based nanoparticles is the metal-organic framework NPs conjugated with HA. These porous materials carry many metal-binding sites that can be used for specific functionalization [106,179]. Their advantages are connected to their high drug loading efficiency due to increased binding surface area [189]. This type of NP is sensitive to different pH conditions, allowing fine-tuning of their release, as demonstrated in a prostate cancer cell model [190].

Combining metal with HA allows the exploitation of specific characteristics of both materials. Thus, AuNPs improve radiotherapy due to gold's ability to adsorb X-rays, demonstrated in animal models [191]. On the other hand, HA allows the restructuring of AuNPs surface, enhancing the ability of the hybrid NPs to conjugate with drugs [192]. Moreover, the combined NPs exhibit superior stability and high-affinity targeting of CD44 positive liver cancer cells in vitro, as shown by Kumar et al. [193]. Furthermore, Dox-HA-super-paramagnetic iron oxide nanoparticles (Dox-HA-SPION) were suggested to enhance the drug efficacy and to minimize off-target effects in MDA-MB-231 human triplenegative breast cancer cells (TNBC) [194]. Liu et al. designed tumor-targeting HA-titanium dioxide (HA-TiO2) nanoparticles loaded with cisplatin (CDDP) with significant anticancer activity in the A2780 ovarian cancer cells [195]. Silica NPs, also classified as inorganic nanomedicines, have many advantages, such as controllable shape and size, low toxicity, and good biocompatibility [196]. Modified with HA silica NPs exhibit increased delivery to HA-receptor expressing cancer cells, as demonstrated in vitro and in vivo [197].
