Exploring the Potentials of Hyaluronic Acid-coated Polymeric Nanoparticles in Enhanced Cancer Treatment by Precision Drug Delivery, Tackling Drug Resistance, and Reshaping the Tumour Micro Environment

Abstract: Cancer is a global health issue that requires modern treatments. Biocompatibility, variable size, and customisable targeting ligands make polymeric nanoparticles (PNPs) a flexible cancer therapy platform. Dynamic nanocarriers, Hyaluronic Acid (HA) coated PNPs, target the overexpressed CD44 receptor in cancer. Through improved permeability and retention, HA, a naturally occurring, biodegradable polymer, increases tumor accumulation and penetration. Hyaluronic acid-grafted polymeric nanoparticles (HA-PNPs) provide a number of advantages over other varieties due to their distinct characteristics. They used CD44 receptor upregulation on cancer cells for selective administration, leveraging the EPR effect for cancer site accumulation. Their natural composition improves biocompatibility while promoting conjugation with a variety of medicinal compounds and providing influence over size and surface features. HA-PNPs facilitate effective cellular uptake, safeguard their cargo, and have the possibility for regulated release, which leads to better delivery of drugs and therapeutic efficacy. While problems, such as CD44 expression variability and drug loading modification, persist, HA-PNPs offer a viable path for targeted and successful treatment of cancer due to their intrinsic benefits. HA-PNPs can be coupled with imaging agents to enable real-time tracking of the delivery of drugs and therapy response, hence enhancing individualized treatment regimens. HA-PNPs can be programmed to respond to particular environmental signals found in the tumor's microenvironment (such as pH, redox potential, and enzymes). This enables for controlled dispensing of therapeutic cargo only when it reaches the target site, reducing systemic exposure and associated negative effects. HA-PNPs have the ability to overcome common MDR processes used by cancer cells, thereby enhancing the efficiency of previously ineffective chemotherapeutic medicines. Recent advances in HA-functionalized PNP fabrication and cancer applications are covered in this article. It discusses complete treatment effectiveness and HA's targeting of tumors and receptors. The study describes production, clinical trials, and problems and prospects in turning HA-coated PNP platforms into viable therapeutic nanomedicines. HA-functionalized PNPs are versatile, targeted nanotherapeutics for various tumor types and disease stages, as shown in this comprehensive study.