Table 2.

TME-responsive vectors in p53 gene therapy.

TME-Responsive Vectors	TME-Sensitive Chemical Bonds or Macromolecules	Targeting Mechanism	Ref.
Redox-responsive vector	Disulfide bond	The high content of GSH in tumor cells can trigger disulfide bond cleavage, thereby releasing drug complexes within tumor cells.	[49]
PH-responsive vector	Hydrazone	The low pH of tumor cells can promote pH-sensitive chemical bond cleavage, thereby releasing drug complexes within tumor cells.	[49]
Enzyme-responsive vector	CPLGIAG peptide	Matrix metalloproteinases (MMPs) are overexpressed in almost all human tumors, and CPLGIAG peptides can be hydrolyzed by MMPs. The drug is coupled to the vector through CPLGIAG peptides, and after entering tumor cells, CPLGIAG peptides are hydrolyzed by MMPs to achieve targeted drug release.	[71]
	Phosphoester bond	The content of phosphodiesterase I in tumor cells is higher than that in normal tissues. Phosphate ester bonds are degraded by phosphodiesterase, and polyphosphate esters rich in phosphate ester bonds are used as p53 gene vectors. After entering tumor cells, the phosphate ester bonds are degraded to release drugs.	[169]
ATP-responsive vector	ATP-responsive aptamer duplex	The level of ATP in the intracellular fluid is higher than that in the extracellular environment. In the ATP rich tumor environment, the structural changes of ATP-responsive aptamer duplex release, thereby targeting the release of loaded drugs.	[170]