Tumor microenvironment-responsive drug self-delivery systems to treat cancer and overcome MDR

Tumor microenvironment-responsive drug self-delivery systems utilize tumor microenvironment-responsive chemical bonds to link anti-tumor drugs, exploiting the hydrophilic and hydrophobic properties of different drugs to form amphiphilic prodrug molecules with self-assembly characteristics. Upon stimulation by specific factors in the tumor microenvironment, these amphiphilic prodrug molecules can release drugs at precise sites within the tumor. These strategies significantly increase the drug concentration at the tumor site while effectively reducing the damage of anti-cancer drugs to normal tissues. Owing to the advanced delivery strategies such as synergistic administration and controlled drug release, tumor microenvironment-responsive drug self-delivery systems hold great potential for treating malignant tumors with multidrug resistance (MDR). At the same time, the stimulus-reactivity of metal complexes provides an important opportunity to design site-specific prodrugs that can maximize therapeutic efficacy while minimizing adverse side effects of metal drugs. This innovative drug design complements the tumor microenvironment-responsive self-delivery system, providing more feasible therapeutic strategies and possibilities in the field of cancer therapy and drug delivery. This work provides a comprehensive review of recent advancements in drug self-delivery systems, offering insights into their potential applications in cancer therapy and MDR reversal.