Table 4.

Multi-stimulus drug delivery systems

Stimulus 1	Stimulus 2	Aim 1	Aim 2	Sequence	Ref.
pH-responsive targeting peptide (R8NLS)	Lysosomal enzyme-responsive sub-units	Positive charge for cellular uptake	Endosomal escape for nuclear targeting	One-by-one	[198]
pH-responsive zwitterionic oligopeptide lipids(pHe)	pH-responsive zwitterionic oligopeptide lipids(pHi)	Positive charge for cellular uptake	Endosomal escape for mitochondrial targeting	One-by-one	[78]
pH-sensitive MPEG-PLA-PAE		Size shrinkage and Positive charge for tumor penetration and cellular uptake		simultaneous	[187]
MMP2-sensitive	pH-triggered	Size shrinkage for tumor penetration	Dox release in lysosome	One-by-one	[116]
ROS-triggered	pH-triggered	Transformation and degradation of polymeric backbone for protein release		One-by-one	[37]
pH-triggered	MMP2-sensitive	CPP re-emergence		simultaneous	[216]
pH-sensitive anionic HPMA copolymer	pH-response hydrazine linkage	Size shrinkage, Positive charge for tumor penetration and cellular uptake	Nucleus entrance	Simultaneous then one-by-one	[177]
MMP-2 responsive peptide	GSH-responsive Au-S bond	Enhanced drug release		simultaneous	[217]
pH-sensitive methylmaleic anhydride	GSH-responsive	Size shrinkage for tumor penetration	Enhanced drug release	one-by-one	[117]
pH-reversal protonation of chitosan		Positive charge for swelling and endosomal escape	Intercellular delivery	one-by-one	[178]