Harnessing nanotechnology for efficient delivery of indole-based drugs in cancer treatment

Indole-based compounds represent an important class of bioactive molecules with proven anticancer potential. However, their clinical translation is hindered by poor solubility, rapid metabolism, systemic toxicity, and limited tumor penetration. Nanotechnology offers promising strategies to overcome these pharmacological and physiological barriers. In this review, we critically evaluate the challenges associated with indole drug delivery and discuss how nanocarrier systems-including liposomes, polymeric nanoparticles, dendrimers, and inorganic platforms-enhance solubility, stability, bioavailability, and tumor selectivity. Special attention is given to tumor extracellular matrix (oncomatrix) properties, which modulate immune evasion and drug diffusion. We also provide a comparative analysis of different nanocarrier platforms, highlighting their advantages, limitations, and translational potential. Finally, future perspectives emphasize the development of barrier-adaptive, stimuli-responsive, and clinically translatable nanomedicines to fully realize the therapeutic promise of indole derivatives in precision oncology. .Emphasis is placed on the strategies for improving tumor-targeting efficiency, stimuli-responsive release, and overcoming biological barriers such as the tumor extracellular matrix and multidrug resistance. Furthermore, we evaluate the current limitations and future directions of indole-loaded nanomedicines with a view toward clinical translation.