Functional nucleic acid-powered hybrid nanocarriers for synchronized targeted delivery of dual-solubility therapeutics

Abstract

Combination chemotherapy presents a promising approach to overcome multidrug resistance in cancer treatment. However, conventional delivery systems struggle to achieve synchronized co-delivery of hydrophilic and hydrophobic therapeutics with tumor-specific targeting and controlled release. Here, we developed a multifunctional nanocarrier integrating poly (lactic-co-glycolic acid) nanoparticles with polydopamine and programmable nucleic acids. Within this system, the hydrophobic core encapsulates lipophilic drugs, while the surface nucleic acid architecture enables hydrophilic drug loading via molecular intercalation. Furthermore, tumor-targeting aptamers guide selective cellular uptake, and a tumor microenvironment-responsive mechanism ensures spatiotemporally controlled drug release. As demonstrated experimentally, this unified platform demonstrates promising antitumor activity with potential advantages in drug delivery efficiency. By combining targeted delivery, differential drug loading, and stimuli-triggered release, the design establishes a modular framework for precision combination therapies, thereby advancing adaptable nanomedicine in oncology.