Table 1.

Applications of Representative CPPs in vivo

Applications of Representative CPPs in Proteins Delivery
CPPs	Sequences	Cargo	Target	Summary
TAT	YGRKKRRQRRR	β-Gal/GDNF/ JNKI1/PSD-95	Brain	β-Gal fused to TAT resulting in strong β-Gal enzyme activity in mice brain; TAT-JNKI1 administration 3 hours after brain ischemia significantly reduced the infarct volume; TAT-PSD-95 protected cultured neurons from excite-toxicity, and reduced focal ischemic brain damage; TAT-GDNF protected brain neurons from cell death when administered after focal cerebral ischemia [76, 79, 80]
TAT-HA	YGRKKRRQRRR-YPYDVPDVA	Bcl-xL	Brain	Administration of TAT-HA-Bcl-xL into mice decreased cerebral infarction in a dose-dependent manner, as determined at 3 d after 90 min of focal ischemia [77]
RDP	KSVRTWNEIIPSKGCLRVGGRCHPHVNGGGRRRRRRRRR	BDNF/β-Gal/Luc	Brain	RDP-BDNF showed the neuro-protective properties in mouse experimental stroke including reduction of stroke volume and neural deficit; The brain slices with X-Gal staining were determined the delivery of RDP-β-Gal across the BBB; The time-course relationship of RDP-Luc was studied to confirm the transport efficiency of RDP [81, 82]
FGF4	AAVLLPVLLAAP	SOCS3	Brain	FGF4-SOCS3 protected mice from lethal effects of staphylococcal enterotoxin B and lipopolysaccharide by reducing production of inflammatory cytokines and hemorrhagic necrosis brain [83]
Applications of Representative CPPs in Nucleic Acids Delivery
CPPs	Sequences	Cargo	Target	Summary
TAT-10H	5H-YGRKKRRQRRR-5H	Plasmid DNA	Brain	5H-TAT-5H/DNA complexes improve up to 7000-fold in BBB across efficiency over the original Tat peptide [87]
RVG-9R	YTIWMPENPRPGTPCDIFTNSRGKRASNG-9R	GAPDH/BACE1 siRNA	Brain	RVG-9R delivered GAPDH/BACE1 siRNA to neurons, microglia, oligodendrocytes in the brain, resulting in a specific gene knockdown [97]
Penetratin	RQIKIWFQNRRMKWKK	APP antisense oligonucleotides	Brain	Penetratin-APP antisense oligonucleotides reduced APP expression and embryonic neural stem cell proliferation in the subventricular zone of the CNS [102]
Applications of Representative CPPs in Small-Molecule Drugs Delivery
CPPs	Sequences	Cargo	Target	Summary
SynB3	RRLSYSRRRF	Morphine-glucuronide	Brain	Enhanced the brain uptake of morphine-glucuronide in in situ brain perfusion [52]
SynB1/SynB3	RGGRLSYSRRRFSTSTGR/RRLSYSRRRF	Dalargin/Paclitaxel	Brain	Enhanced dalargin in brain uptake, resulting in a significant improvement of anti-nociceptive effect [109]
SynB1/SynB5	RGGRLSYSRRRFSTSTGR/RGGRLAYLRRRWAVLGR	Doxorubicin	Brain	Significantly increase the uptake of doxorubicin into the brain [110]
SynB1/D-Penetratin	RGGRLSYSRRRFSTSTGR/RQIKIWFQNRRMKWKK	Doxorubicin	Brain	20-fold increase of doxorubicin in brain parenchyma by using a capillary depletion method, [111]
Angiopep-2	PFFYGGSGGNRNNYLREEY	Paclitaxel	Brain	Angiopep-2-paclitaxel showed activity in heavily pretreated patients with brain metastases and/or failed prior taxane therapy [115]
Angiopep-5	RFFYGGSRGKRNNFRTEEY	Doxorubicin	Brain	Angiopep-5-doxorubicin exhibited dramatically higher BBB influx rate constants than doxorubicin and pooled within brain parenchymal tissue [113]
Applications of Representative CPPs in Nanoparticles Delivery
CPPs	Sequences	Cargo	Target	Summary
TAT	YGRKKRRQRRR	Qdots	Brain	TAT-Qdot was loading sufficiently high in brain that a gross fluorescent can be visualized using a low power UV lamp [117]
TAT-Liposome	YGRKKRRQRRR- Liposome	Coumarin-6	Brain	TAT-LIP was a promising brain drug delivery system due to its high delivery efficiency across the BBB [121]
TAT-cholesterol	YGRKKRRQRRR -cholesterol	G(3)R(6)	Brain	FITC-loaded cholesterol-conjugated G(3)R(6)-TAT can cross BBB, and is a promising antimicrobial agent for treatment of brain infections caused by C. neoformans [120]
TAT-PEG-cholesterol	YGRKKRRQRRR-PEG -cholesterol	Ciprofloxacin	Brain	TAT-PEG-cholesterol were effective for delivery of ciprofloxacin across the BBB [119]
RVG-BPEI-SS	YTIWMPENPRPGTPCDIFTNSRGKRASNG-BPEI-SS	cy5.5-miR-124a	Brain	The RVG combined with BPEI-SS for neuron-specific targeting in vivo is sufficient to deliver neurogenic microRNA (e.g. cy5.5-miR-124a) into the brain [98]
(RXRRBR)2XB	RXRRBRRXRRBRXB	AMO	Brain	Systemic administration of (RXRRBR)2XB-AMO in mice showed efficient uptake in the brain, which can dramatically improve ATM splicing correction efficiency [101]
Angiopep-2-PEG	PFFYGGSGGNRNNYLREEY-PEG	Paclitaxel -Alexa488	Brain	Fluorescent microscopy revealed that Angiopep-2 modified PEG nanoparticle deliver Alexa488 labeled paclitaxel across BBB, and localized in brain endothelial cell monolayers [112]
Angiopep-2-O-MWNTs-PEG	PFFYGGSGGNRNNYLREEY-O-MWNTs-PEG	Doxorubicin	Brain	Fluorescence imaging demonstrated that Angiopep-2-O-MWNTs-PEG constituted an ideal dual-targeting drug delivery system to deliver doxorubicin for the treatment of brain tumor [114]