Hyaluronic Acid-Polyethylene Glycol-Polycaprolactone Nanocarriers: Accurate Targeting and Multimodal Treatment for Aggressive Cancers
Devansh Shah, Aryan Thakkar, Sankha Bhattacharya
Abstract
Hyaluronic acid-functionalized polyethylene glycol-polycaprolactone (HA-PEG-PCL) copolymers are emerging as a highly effective nanocarrier platform for targeted cancer therapy. These multifunctional systems integrate tumor-specific targeting, controlled drug release and enhanced pharmacokinetics to address the limitations of conventional chemotherapy. By exploiting the overexpression of CD44 receptors on malignant cells, HA-PEG-PCL nanoparticles achieve selective uptake and accumulation within tumors, minimizing off-target toxicity. The copolymer’s amphiphilic structure allows for efficient encapsulation of both hydrophobic and hydrophilic therapeutics, while modifications such as pH-sensitive bonds and redox-responsive linkers enable site-specific release within the tumor microenvironment. Preclinical studies across multiple cancer models including breast, colorectal and liver cancers demonstrate significant improvements in tumor inhibition, survival rates and metastasis reduction. Furthermore, the platform’s adaptability to gene therapies and immunomodulators positions it as a promising candidate for personalized and combination oncology treatments. Despite some challenges in large-scale production and potential immunogenicity, ongoing innovations in synthesis and functionalization are rapidly advancing HA-PEG-PCL systems toward clinical application.