Recent Advances in Small-Molecule-Based Nanovectors for the Treatment of Colorectal Cancer

Abstract

Colorectal cancer (CRC) remains a major global health burden, while conventional systemic therapies are limited by toxicity, drug resistance, suboptimal tumour exposure, and pharmacokinetic constraints. Recent advances in nanotechnology have produced diverse nanosystems including liposomes, dendrimers, polymeric nanoparticles, metallic nanoparticles, mesoporous silica systems, and other hybrid platforms that can improve drug solubility, stability, biodistribution, controlled release, and tumour-directed delivery. Plant-derived small molecules provide an additional source of structurally diverse anticancer candidates, but their clinical development is often constrained by poor aqueous solubility, rapid metabolism, limited bioavailability, and non-specific toxicity. This review critically examines recent progress in nanoscale delivery systems for CRC and evaluates their potential for delivering plant-derived and other bioactive small molecules. Particular emphasis is placed on passive and active targeting, physicochemical determinants of delivery, platform-specific advantages and limitations, preclinical evidence, and the barriers to clinical translation. The review also highlights the distinction between plant-derived and fungal-derived natural products and identifies opportunities for integrating natural products with responsive and ligand-functionalized nanocarriers.