Review Article

Delivery of Nucleic Acids and Nanomaterials by Cell-Penetrating Peptides: Opportunities and Challenges

Table 3

Pharmacological and physical inhibitors of cellular uptake process.

InhibitorMechanismWorking conditionRef.

Low temperatureInhibit energy-dependent endocytosis4°C[17]
Hypertonic mediumInhibit clathrin-dependent endocytosis
(Dissociate clathrin lattice)
0.2–0.45 M sucrose[17, 50]
Potassium depletionInhibit clathrin-dependent endocytosis
(Dissociate clathrin lattice)
50% DMEM w/1 mM ouabain[50]
FusicoccinEndocytosis inhibitor
(H+-ATPase activator)
10 M[51]
Valinomycin/nigericinInhibit energy-dependent endocytosis
(Na+/K+ ATPase modulator; K+ selective ionophore)
2 M[52, 53]
Sodium azide/sodium fluoride/antimycin A Inhibit energy-dependent endocytosis
(All metabolic inhibitors)
(0.15%/15 mM/2 g/mL)[17]
Okadaic acidEndocytosis and autophagy inhibitor 1.5 M[4, 26]
NocodazoleInhibit clathrin-dependent endocytosis
(Cause microtubule depolymerization)
10–25 M[17, 54]
Latrunculin AInhibit micropinocytosis
(F-actin depolymerization inhibitor)
15 M[55]
Cytochalasin D (CytD)Inhibit macropinocytosis, clathrin- and caveolae-dependent endocytosis
(Inhibit F-actin rearrangement)
1–30 M[5658]
N-Ethylmaleimide (NEM)Inhibit clathrin- and caveolin-dependent endocytosis
(Inhibit endosomal fusion, energy metabolism)
0.1–3 mM[5961]
Methyl--cyclodetritrin (MCD)Inhibit clathrin- and caveolae-dependent endocytosis
(Deplete or sequester cholesterol)
2 mM[62]
FilipinInhibit caveolae-dependent endocytosis
(Inhibit lipid raft; cholesterol binding)
5 g/mL[63]
NystatinInhibit caveolae-dependent endocytosis
(Inhibit lipid raft; sequester cholesterol)
5 g/mL[63]
WortmanninInhibit receptor-mediated endocytosis
(Inhibit PI-3 kinase)
100 nM[64]
5-(N-Ethyl-N-isopropyl)-amiloride (EIPA)Inhibit micropinocytosis
(Inhibit Na+/H+ exchanger)
100 M[65]
Dextran sulfateInhibit binding of CPP to cell membrane5 g/mL[66]
DMSO/ethanolDirect membrane translocation enhancer10%/1%[43]
Oleic acid/limonene/PEGAll direct membrane translocation enhancers5%[28, 43]
ChloroquineLysosomotropic agent
(Cause vesicular lysis)
100 & 25 M[67, 68]
Ammonium chloride Inhibit the fusion of lysosomes with endosomes10 mM[67, 69]