*3.2. Chondroitin Sulfate and Dermatan Sulfate-Based Nanoparticles as Drug Delivery Systems*

CS exhibits high biocompatibility and specific localization, being bound to PGs in ECMs of tissues such as cartilage, blood vessel walls, skin, and tendons [48]. In line with increasing nanotechnology application, optimally designed nano-scaled carriers on the base of CS have been developed, exhibiting unique properties, such as biocompatibility, low toxicity, and active and passive targeting. Their specific properties and discrete modalities make them promising drug delivery vehicles for cancer therapy [145].

Because CS, like all GAGs, is a specific anionic acid polysaccharide, it couples well with cationic poly-saccharides, including chitosan, which as a natural molecule is likewise characterized with good bioactivity [146]. Thus, a CS–chitosan nanoparticle carrier encapsulating black rice anthocyanins exhibited significant apoptosis-inducing effects in colon cancer cells [147], whereas loading these nanoparticles with curcumin induced a cytotoxic effect in the lung cancer model [148].

Moreover, loaded with camptothecin (CPT) polymeric nanoparticles functionalized with CS exerted targeted colon cancer drug delivery with superior anticancer effects compared to non-targeted nanoparticles [149]. This approach utilized CS's affinity for the CD44 HA receptor overexpressed in various tumors [107].

Notably, CS can lower the adverse side effects of chemotherapeutic drugs as CS-Doxpoly(lactic-co-glycolic acid) (PLGA)conjugated nanoparticles exhibited lower cardiotoxicity and enhanced tumor inhibition compared with free Dox [150]. This development is an important achievement as cardiac toxicity through various mechanisms is a severe drawback of Dox utilization [151,152].
