Table II.

Examples of bystander uptake under preclinical development

Bystander Inducer	Description	Result	Reference
TAT	TAT co-incubation could provoke the uptake of the macropinosytosis marker 70kDa Dextran.	in vitro	[73]
TAT-NPs	NPs conjugated with TAT could induce bystander uptake of all NP-type cargo but not common fluid markers, the activity of which was regulated by extracellular cysteine presence both in vitro and in vivo.	in vitro & in vivo	[8]
Polyarginines	TAT-fused albumin induced macropinocytosis through interactions with HSPG and CXCR4 to activate PKC/PI3K/JNK/mTOR signaling pathways.	in vitro	[72]
iRGD	iRGD could facilitate the delivery of small molecule, nanoparticle and antibody into tumors when administered as a combination therapy.	in vivo	[59]
	Despite little enhancement of cytotoxicity in vitro, co-administered iRGD promoted the delivery of PLGA nanoparticles selectively into tumors in vivo.	in vitro & in vivo	[78]
LyP-1	The LyP-1-containing self-microemulsifying formulation not only increased in vitro cytotoxic effect of co-administered doxorubicin hydrochloride, but also achieved preferential accumulation in tumors via intraperitoneal injection.	in vitro & in vivo	[79]
tLyP-1	Following tLyP-1 co-administration, tumor-targeted NPs displayed improved cytotoxicity of the loaded paclitaxel and deeper penetration into the glioma parenchyma.	in vitro & in vivo	[80]
iNGR	iNGR enhanced accumulation and efficacy of co-administered doxorubicin by triggering the tumor-specific penetration.	in vivo	[82]