Progress in polymeric nanoparticle-based treatment approaches for Wnt β-catenin pathway modulation and adenomatous polyposis coli mutant colorectal cancer.
Abstract
About 80-90% of sporadic instances of colorectal cancer (CRC) are caused by mutations in the adenomatous polyposis coli (APC) gene, which is one of the earliest and most common molecular events. The constitutive activation of the Wnt/β-catenin signalling pathway caused by APC dysfunction promotes unchecked cellular proliferation, tumour initiation, progression, and treatment resistance. Systemic toxicity, insufficient tumour selectivity, and acquired drug resistance continue to restrict treatment results for advanced colorectal cancer (CRC) despite advancements in surgery, chemotherapy, targeted treatments, and immunotherapy. Novel treatment approaches that can address the molecular anomalies linked to APC dysfunction are therefore desperately needed. In this context, a number of treatment modalities have been studied, including small interfering RNA (siRNA), microRNA, CRISPR/Cas-based gene-editing systems, chemotherapeutic drugs, and combination therapy. Polymeric nanoparticles (PNPs) are among the strategies that have shown promise as preclinical delivery systems and have the potential to be translated into clinical settings. Poly(lactic-co-glycolic acid) (PLGA), chitosan, and PEG-based polymeric nanoparticles (PNPs) offer biocompatibility, controlled release, enhanced tumour accumulation, and protection of therapeutic cargo. In addition to critically assessing PNP-mediated medication and gene delivery techniques that target APC-associated Wnt/β-catenin signalling, this review explores the mechanistic significance of APC in colorectal carcinogenesis. The promise of PNPs to enhance APC-focused treatment in colorectal cancer is highlighted by emphasising targeted delivery, therapeutic precision, biomarker-guided techniques, translational hurdles, and future clinical prospects.
