Table 2.

Structural change strategies.

	System name	Mechanisms	Experimental animal model	Size changes (nm)	Penetration Model/imaging methods in Tumors	Ref.
External physical stimulation	HBPTK-Ce6@CPT	ROS & light triggered size-reduction	HT29 xenografts tumor-bearing nude mice	210-110-40	HT29 MCSs and frozen sections	[182]
	PDA@GNRs-DOX/Ce6	NIR light triggered size conversion	U14 tumor-bearing mice	440-150-50	Real-time thermal imaging in vivo	[181]
	ICG@HSA-Azo-HP	Photothermal triggered size-shrinkage	4T1 tumor-bearing mice	140–11	4T1 multicellular tumor spheroids (MTSs) and frozen sections	[184]
	DAT-PPED&F	Magnetic actuated TAT reactivation	MDA-MB-231 xenograft tumor tissue	180-100 (acceptable deformation penetration diameter)	Ex vivo visualized via CLSM	[54]
	ADM-GNMF	Ultrasound triggered response	/	46 $\pm$ 12-1212$\pm$ 35 (drug release)	/	[190]
Tumor internal environment response	PDPP@D	Neighboring effect triggered by pH/redox conditions	4T1tumor-bearing mice	60	4T1 MTS and frozen sections	[42]
	GFLG-DP	CTSB triggered stealthy-to-sticky conversion	4T1 tumor-bearing mice	150-80-20	4T1 MCSs and in vivo real-time imaging	[205]
	IDDHN	HAase triggered size shrinkage	4T1 breast cancer-bearing mice	264-(most at 29–50)	4T1 MCSs and ex vivo imaging	[153]
	UAMSN@Gel-PEG	MMP-2 triggered size shrinkage	4T1 tumor-bearing mice	76–6.5	Ex vivo and visualized by CLSM	[63]
	iCluster/Pt	Intrinsic tumor extracellular acidity triggered structural alteration	BxPC-3 pancreatic tumor-bearing mude mice	100-(∼5) (release small PAMAM prodrugs)	BxPC-3 MCSs and histological analyses	[204]
	SCNs/Pt	pH triggered size transition	BxPC-3 xenografts tumor-bearing mice	80-(less than 10)	BxPC-3 MCSs and real-time imaging by intravital CLSM	[162]
	SA-DOX@HA-CD	pH triggered self-disintegration of nanoassemblies	4T1 tumor-bearing BALB/c mice	(150–200)-(30–40)	4T1 tumor spheroids and fluorescence imaging	[203]