TABLE 1.

Advantages and disadvantages of different types of stimulus-responsive NDDSs.

Stimuli-responsive NDDSs	Advantages	Disadvantages	References
pH-responsive NDDSs	Better at penetrating the biomembrane	Can be easily recognized by opsonins in the plasma and thus cleared	Yan and Ding (2020), Chen et al. (2023)
Enzyme-responsive NDDSs	More suitable for the complex TME.	It lacks the specificity required for targeted cancer immunotherapy; nonspecific enzyme activity can cause off-target effects; and it is difficult to precisely control the kinetics of enzymatic reactions	Peng et al. (2022), Li et al. (2020a), Shahriari et al. (2019)
ROS-responsive NDDSs	Suitable for combination with tumor-targeted therapy	Lacks selectivity because the redox conditions in both healthy and pathological tissues can cause the unintended release of the immunotherapy agent	Li et al. (2020b), Yang and Sun (2022), Li et al. (2020c)
Ultrasound-responsive NDDSs	Can control the timing of drug release and allow for repeated dosing	Due to the limitations in penetration capability, they are difficult to achieve precise spatial localization	Xiu et al. (2023), Cheng et al. (2021), Zhou et al. (2020)
Light-responsive NDDSs	Can remotely trigger drug release in an on-off manner	Affected by tissue depth, the effective range is limited	Kang et al. (2023), Chen and Zhao (2018)