Table 2.
Peptide-functionalized liposomal formulations entrapping anticancer drug and diagnostic agents for targeted therapy of cancer
| Surface attached peptide | Anticancer agent | Liposome formulation | Targeted cancer type | Peptide target site or activity | Size (nm) | Reference |
|---|---|---|---|---|---|---|
| Arginine unit (R8) | DOX | HSPC:Chol:mPEG-DSPE:RhPE (molar ratio 59:38.21:2:1) | Ovarian carcinoma (in vitro and in vivo) | CPP-facilitated delivery of anticancer agent | 214.5 | [139] |
| Peptide S1 (LIDHEWKENYFPLSF) | DOX | SPC:Chol: S1-PEG2000-DSPE and DOX ( weight ratio 8:1:1:1 w/w/w/w) | Tumor-associated angiogenesis (in vitro and in vivo) | VEGFR2 receptor | 143 | [17] |
| P1 peptide (TVRTSAD) | DOX | DPPC: DPPG-Na: DPPE-PDP:Chol: Chol-PEG (15:15:30; 4:36 molar ratio) | Gastric cancer (in vivo) | CLDN7 marker protein | 160 | [19] |
| Fatty acid-conjugated, elastin-like peptide (FELP) | DOX | DPPC: DSPE-PEG: Cholesterol: FELP at a 55:2:15; 0.4125 molar ratio | Non-thermal acoustic cancer treatment (in vitro and in vivo) | Tumor site-specific drug delivery | 134.97 | [140] |
| pH responsive CPP H7K(R2)2 | DOX | DOPE: CHEMS: DSPE-PEG and DSPE-PEGH7K(R2)2 | Glioma tumor (in vitro and in vivo) | CPP-facilitated delivery of anticancer agents in gliomas | 92.19 | [87] |
| Integrin α5β1 antagonist (Ac-PHSCN-NH2) | DOX | HSPC/DPPE /Chol/OHCPEG-CHO (15:5:10:10 mole ratio) | Melanoma B16F10 cells (In vitro and in vivo) | Targeted-drug therapy toward integrin α5β1 receptor | 96.0 | [141] |
| Cell penetrating peptide (CPP) | DOX | SPC/Chol/DSPE-PEG2000 (100:50:8 mol/mol/mol) | Human breast cancer tumor (in vitro and in vivo) | CPP-facilitated delivery of anticancer agents in breast cancer. | 121.25 | [94] |
| TAT cell-penetrating peptide | DOX | 1.5% dsPe-PeG2000, 1% dsPe-PeG2000-tat, 2.5% dsPe-PeG2000-ang, 59% SPC, 36% CHO | Glioma cells (in vitro) | Low-density lipoprotein receptor related protein-1 (LRP1) | 93.7 | [142] |
| DCDX and c(RGDyK) peptides | DOX | HSPC/cholesterol/mPEG2000-DSPE/DCDX-PEG3400-DSPE/ c(RGDyK)-PEG3400-DSPE (52/43/2/2/1, by mole) | Glioma (in vitro and in vivo) | Nicotine acetylcholine receptors (nAChRs) on the BBB and integrin highly expressed on the BBTB and glioma cells | 93.9 | [143] |
| APRPG | miRNA and DOX | DOPE, cholesterol, DPPC, and DCP-TEPA (4:4:3:1 as a molar ratio) | Colon (in vitro and in vivo) | VEGFR-1 | 163 | [144] |
| RIV (DFDSDMDEDGDIDHDQ DGDQDHDPDKDIDRDM DIDQDMDTDI) | DOX and CA-4 | Hydrogenated soybean phosphatidylcholine/cholest erol, 55/45, mol/mol | Skin (in vitro and in vivo) | VEGFR-2 | 70–110 | [145] |
| RIPL peptide (IPLVVPLRRRRRRRRC) | DTX | PC, TW80, and DP2KM (8.8:1:0.2 molar ratio) | Prostate and ovarian tumor (in vitro and in vivo) | Targeted delivery to hepsin-expressing cancer cells | 162.4 | [146] |
| LDV and YSA peptides | DTX | DOPC, Cholesterol, C16-LDV, C16-YSA, DX (16:4:8:8:1 ratio) | Melanoma cell (in vitro) | Integrin (α4β1) and ephrin (EphA2) receptors | - | [55] |
| Histidine tagged EphA2 receptor specific peptide (YSA) | DTX | DTX:DOGS-NTA-Ni:DOPC:Cholesterol:DSP E-PEG 2000 (0.5:5:20:5:2.5 weight ratio) | Lung cancer (in vitro and in vivo) | EphA2 receptor | 189.3 | [147] |
| Angiopep-2 and tLyP-1 peptides | DTX & VEGF siRNA | DOTAP:SPC:Chol:DSPE-PEG2000 (25:40:30:4, mol/mol) | Brain tumor glioma cell (in vitro and in vivo) | Protein receptor (angiopep-2) and neuropilin-1 receptor (tLyP-1) | 110 – 150 | [148] |
| ELP and tethered GRP | DTX | 1.5× ELP-GRP/C/ACD-1/DTX | Prostate cancer cells (in vitro) | Gastrin-releasing peptide receptor (GRPR) | 23.5 – 154.8 | [149] |
| CPP Penetratin | 5-FU and Tf | DOTAP/DOPE/ CHEMS /Pen-PEG(2000)-DSPE (43.5:43.5:5:4 mole %) | Brain tumor glioblastoma cell (in vitro) | Transferrin (Tf) receptors in brain tumors | 178.12 | [150] |
| PR_b | 5-FU | (65-xy):35:x:y mol% of DPPC:CHOL:PEG:peptide-amphiphile, where x is the indicated mol% of PEG and y is the mol% of peptide-amphiphile | Colon cancer cells (in vitro) | Integrin α5β1 | 80 – 150 | [60, 66] |
| YIGSR peptide | 5-FU | DSPC/CH/DSPE-PEG(2000)-MPB (6:4:0.5) | Angiogenic endothelial cells (in vitro and in vivo) | Laminin receptors | 103 | [151] |
| Cyclic RGD peptide | 5-FU | DSPC/cholesterol/DSPE – PEG – RGD (56:39:5) | Angiogenic endothelial cells (in vitro and in vivo) | avb3 integrins | 105 | [152] |
| Peptide AA13 | DNR | S100PC/CHOL/mPEG2000-DSPE (4:1:0.2, molar ratio) | Acute myeloid leukemia (AML) cells (in vitro and in vivo) | Low density lipoprotein receptor (LDLR) | 95 | [153] |
| Arginine8-Glycine-Aspartic acid (R8GD) peptide | DNR and emodin | EPC, Chol, DSPE-PEG2000, emodin and DSPE-PEG2000-R8GD at a mass ratio of 100:25:8:6:40 | Cancer therapy (in vitro and in vivo) | Vasculogenic mimicry (VM) channels | 100 | [154] |
| PFV peptide | DNR and dioscin | EPC, Chol, DSPE-PEG2000, DSPE-PEG2000-PFV and dioscin (100:30:3:2:7, molar ratio) | Non-small-cell lung cancer (NSCLC) (in vitro and in vivo) | Vasculogenic mimicry (VM) channels and tumor metastasis | 121.13 | [155] |
| R8-dGR peptide | PTX | SPC, cholesterol and DSPE-PEG2000-OMe (molar ratio = 62:33:5) | Malignant melanoma (in vitro and in vivo) | Neuropilin-1 receptors and integrin αvβ3 receptors | 100 | [156] |
| Glu6-RGD peptide | PTX | SPC/cholesterol/Ligand Glu6-RGD-Chol (molar ratio = 62:33:3) | Bone metastatic breast cancer (in vitro and in vivo) | αvβ3 integrin | 121.9 | [56] |
| RGD peptide | PTX and CUR | PTX (5 mg), CUR (3 mg), CHOL (15 mg), DSPE-PEG 2000 (12.5 mg) and SPC (120 mg) | Lung cancer (in vitro and in vivo) | α5β3 integrin | 120.6 | [57] |
| TR peptide | PTX | SPC, Cho, DSPE-PEG2000OMe, DSPE-PEG2000-peptide (59:33:2:6, molar ratio) | Glioma (in vitro and in vivo) | α5β3 integrin | 131.8 | [58] |
| Peptide R8-RGD | PTX | SPC/cholesterol/DSPE-PEG2000/DSPE-PEG2000- R8-RGD (molar ratio ¼ 62: 33:4.2:0.8) | Glioma (in vitro and in vivo) | α5β3 integrin | 105.9 | [59] |
| CAP peptide | PTX and albumin nanoparticles | 2.5 mg of DPPC, 0.1 mg of CAP, 0.51 mg of DSPE-PEG2KOMe, and 0.2 mg of IR-780 | Pancreatic ductal adenocarcinoma (PDAC) (in vitro and in vivo) | Membrane biomarker FAP-α | 123.9 | [157] |
| TH peptide | PTX and αGC immunoadjuvant | Cholesterol/SPC/DSPE-PEG2000/DSPE-PEG2000-TH (molar ratio = 33:59:2:6) | Melanoma (in vitro and in vivo) | pH-responsive delivery of anticancer agent in melanoma | 118.3 | [158] |
| Cell-penetrating peptide TAT | PTX and DOX | SPC, CHO,DSPE-PEG2000, DSPE-PEG1000-TAT, DSPE-PEG3500-Tf in 60, 33, 3, 2, 2 % respectively. | Melanoma (in vitro and in vivo) | CPP-facilitated delivery of anticancer agent | 124.5 | [159] |
| CPP PFVYLI | PTX | 15.9 mg of EPC, 4.1 mg of Chol, 4.7 mg of PEG2000DSPE and 1.5 mg of PFVPEG2000-DSPE | Breast cancer (in vitro and in vivo) | CPP-facilitated delivery of anticancer agent | 120 | [160] |
| TH peptide | PTX and LST | SPC, Cholesterol, DSPE-PEG2000-OMe and DSPE-PEG2000-TH (molar ratio = 59:33:2:6) | Breast cancer (in vitro and in vivo) | pH-responsive delivery of anticancer agent in breast cancer | 109.3 | [161] |
| Peptide H7K(R2)2 | PTX and SPIO NPs | PTX, EPC, cholesterol, DSPE-PEG, and DSPE-PEG-H7K(R2)2 | Breast cancer (in vitro and in vivo) | pH-responsive delivery of anticancer agent in breast cancer | 168.30 | [20] |
| Gonadorelin peptide | MXT | HSPC, cholesterol, and mPEG 2000-DSPE in a mole ratio of 90:10:0.4 | Breast cancer (in vitro and in vivo) | Luteinizing hormonere-leasing hormone targeted delivery of anticancer agent | 118.7 | [162] |
| RGD and ATWLPPR peptide | Gd-DTPA | Egg PC/ cholesterol/ mPEG2000-DSPE at a molar ratio of 1.85/1/ 0.15 | Tumor tissue - (in vitro and in vivo) | Angiogenesis targeting molecular imaging of tumor | 103.50 | [163] |
| cRGD peptide | Iron oxide (Fe3O4) nanoparticles | DMPC: DMPG (9:1) in TES buffer were mixed at a lipid/ Fe3O4 weight ratio of 1:5 | Glioma and ovarian cancer (in vitro and in vivo) | α5β3 integrin | 57.8 | [164] |
| Anti-HER2 peptide | Methylene blue (MB) attached NaYF4:Yb,Er upconversion nanoparticles (UCNPs) | 500 μL soy lecithin (10 mM) and 47% cholesterol | Breast cancer (in vitro and in vivo) | HER2-positive breast cancer | 90.0 | [165] |
| L-peptide (RLLDTNRPLLPY) | Rhenium-188 (188Re) radioisotope | Peptide-PEGylated-liposomes (1 ml) were added to a solution of 188Re-BMEDA (50–250 MBq), and incubated at 60 ºC for 30 min | Nasopharyngeal carcinoma (in vitro, in vivo and, in silico) | GRP78, a specific cancer cell-surface marker | - | [166] |
| Bombesin peptide | Technetium-99m (99mTc) isotope | DOPE, CHEMS, and DSPE-PEG2000 (lipid concentration 40 mM; molar ratio5.7:3.8:0.5, respectively | Breast cancer (in vitro and in vivo) | Different tumors including lung, prostate, breast, pancreas, and colon tumors, express receptors for these peptides [167] | 124.1 | [168] |
Abbreviations: CPP, cell-penetrating peptide; Chol, cholesterol; CUR, Curcumin; CHEMS, cholesteryl hemisuccinate; DSPE-PEG2000, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[poly(ethylene glycol) 2000]; DOX, doxorubicin; DTX, docetaxel; DNR, daunorubicin; DPPC, DPPG-Na, dipalmitoyl phosphatidylglycerol dipalmitoyl phosphatidylcholine; DPPE-PDP, (N-[3-(2-pyridinyldithio)-1-oxopropyl]-L-a-dipalmitoyl phosphatidylcholine; DOPE, dioleoylphosphatidylethanolamine; DOTAP, 1,2-dioleoyl-3-trimethylammonium-propane chloride; DSPC, distearoylphosphatidylcholine; DMPG, 1,2-Dimyristoyl-sn-glycero-3-phosphorylglycerol sodium salt; DMPC, 1,2-Dimyristoyl-sn-glycero-3-phosphocholine; ELP, elastin-like polypeptide; EPC, egg yolk phosphatidylcholine; GRP, gastrin-releasing peptide; Gd-DTPA, gadolinium-diethylenetriamine pentaacetic acid; HSPC, hydrogenated soy phosphatidylcholine; LST, losartan; PTX, paclitaxel; RhPE, rhodamine-PE; SPC, soy phospholipids; SPIO NPs, superparamagnetic iron oxide nanoparticle; Tf, transferrin; TES, 2-[(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)amino]ethanesulfonic acid; VEGF, vascular endothelial growth factor; 5-FU, 5-fluorouracil, MXT, mitoxantrone.