Poly Beta-Amino Esters Nanoparticles as a Promising Strategy for Colon Cancer Therapy: Covering Synthesis Mechanisms, Characterization, Preclinical and Clinical Progress, and Regulatory Challenges.

Colon cancer is still one of the biggest health challenges globally, and most of the available treatments are hindered by drug resistance, systemic toxicity, and suboptimal efficacy. The Poly (beta-amino esters) (PBAE)-based nanoparticles have emerged as a promising nanotechnology-driven solution to these challenges. This review begins with the synthesis and functionalization of PBAE nanoparticles by focusing on polymerization techniques, targeting strategies, and scalability for clinical applications. The physicochemical properties of these nanoparticles, such as particle size, surface morphology, zeta potential, stability, biodegradability, and drug loading efficiency, are discussed in relation to their impact on therapeutic performance. Mechanistic insights into drug encapsulation, controlled release, tumour targeting, and the potential to overcome Multidrug Resistance (MDR) are also provided. Mechanistic insights are provided, including hydrophobic interaction-based drug encapsulation for efficient drug loading, pH-responsive controlled release in acidic tumor microenvironments, receptor-mediated tumour targeting using surface-functionalized ligands, and strategies to overcome Multidrug Resistance (MDR). Thereafter, preclinical studies are assessed, which include in-vitro cytotoxicity experiments and in-vivo animal models that test for efficacy, pharmacokinetics, and biodistribution. The review will then assess the status of PBAE nanoparticles in clinical trials, focusing on safety, efficacy, and the effects on patient outcomes in colorectal cancer treatment. Finally, regulatory approval, toxicity assessments, and commercialization challenges are discussed along with recommendations for overcoming these barriers. The review concludes by highlighting advancements in nanoparticle design, emerging therapeutic strategies, and the future potential of PBAE nanoparticles to transform colorectal cancer treatment.