Smart on-demand drug release strategies for cancer combination therapy

In cancer therapy, enhancing therapeutic indices and patient compliance has been a central focus in recent drug delivery technology development. However, achieving a delicate balance between improving anti-tumor efficacy and minimizing toxicity to normal tissues remains a significant challenge. With the advent of smart on-demand drug release strategies, new opportunities have emerged. These strategies represent a promising approach to drug delivery, enabling precise control over the release of therapeutic agents in a programmed and spatiotemporal manner. Recent studies have focused on designing delivery systems capable of releasing multiple therapeutic agents sequentially, while achieving spatial resolution in vivo. Smart on-demand drug release strategies have demonstrated considerable potential in tumor combination therapy for achieving precision drug delivery and controlled release by responding to specific physiological signals or external physical stimuli in the tumor microenvironment. These strategies not only improve tumor targeting and reduce toxicity to healthy tissues but also enable sequential release in combination therapy, allowing multiple drugs to be released in a specific spatiotemporal order to enhance synergistic treatment effects. In this paper, we systematically reviewed the current research progress of smart on-demand drug release drug delivery strategies in anti-tumor combination therapy. We highlighted representative integrated drug delivery systems and discussed the challenges associated with their clinical application. Additionally, potential future research directions are proposed to further advance this promising field.