A Review on Cell Penetrating Peptides: Golden Chariots for Anti-Cancers Agents Delivery in Cancer Therapy
الموضوعات :
Pooneh Mahboub
1
(Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran)
Mahsa Rasekhian
2
(Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran)
soheila Mohammadi
3
(Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran)
الکلمات المفتاحية: Targeted drug delivery, Cell-penetrating peptide, Cancer ,
ملخص المقالة :
Cancer has been one of the most prevalent causes of death around the world and despite the development of new therapeutic methods, traditional treatments including chemo and radiotherapy are still the pillars of cancer treatment. However, serious side effects and invasiveness limit the application of traditional cancer methods. To reduce the debilitating side effects of chemotherapy agents, targeted delivery of drugs to malignant cells has been the focus of much research in several past decades. Such efforts however have to overcome serious obstacles. Targeted delivery strategies have been applied to a wide range of cargos including nucleic acid base therapeutic molecules, peptides, and proteins as well as small molecule drugs. Recently, Cell Penetrating Peptides (CPPs) have been indicated as ideal transporters due to their desirable transitional features. CPPs are small synthetic or organic vehicles with the ability to form covalent or non-covalent bonds with a wide variety of substances. The capability of CPPs in crossing cell membranes, has received well-deserved attention in designing novel diagnoses and therapeutic strategies. In this review article, we compared structurally similar carriers designed by different research groups and discussed their strengths and limitations. The comparison was mainly based on the sequence properties of CPPs. We further discussed CPPs according to their cargo and reviewed their application in “in vivo” research. Research shows that despite the significant progress, drug delivery by CPPs has to address several issues, and such challenges have paved the way for further studies in the CPP field.
1. McClorey G., Banerjee S., 2018. Cell-penetrating peptides to enhance delivery of oligonucleotide-based therapeutics. Biomedicines. 6(2), 51.
2. Xie J., Bi Y., Zhang H., Dong S., Teng L., Lee R.J., Yang Z., 2020. Cell-penetrating peptides in diagnosis and treatment of human diseases: from preclinical research to clinical application. Frontiers in Pharmacology. 11, 697.
3. He L., Sayers E., Watson P., Jones A., 2018. Contrasting roles for actin in the cellular uptake of cell penetrating peptide conjugates. Scientific Reports. 8(1), 7318.
4. Guo Z., Peng H., Kang J., Sun D., 2016. Cell-penetrating peptides: Possible transduction mechanisms and therapeutic applications. Biomedical Reports. 4(5), 528-534.
5. Gara E., Csikó K. G., Ruzsa Z., Földes G., Merkely B., 2019. Anti-cancer drugs-induced arterial injury: risk stratification, prevention, and treatment. Medical Oncology. 36, 1-8.
6. Tang H., Zhao W., Yu J., Li Y., Zhao C., 2018. Recent development of pH-responsive polymers for cancer nanomedicine. Molecules. 24(1), 4.
7. Yan Y., Ding H., 2020. pH-responsive nanoparticles for cancer immunotherapy: a brief review. Nanomaterials. 10(8), 1613.
8. Zhao Y., Cai F., Shen X., Su H., 2020. A high stable pH-temperature dual-sensitive liposome for tuning anticancer drug release. Synthetic and Systems Biotechnology. 5(2), 103-110.
9. Sherr C.J., Bartek J., 2017. Cell cycle–targeted cancer therapies. Annual Review of Cancer Biology. 1, 41-57.
10. Bighetti-Trevisan R.L., Sousa L.O., Castilho R.M., Almeida L.O., 2019. Cancer stem cells: powerful targets to improve current anticancer therapeutics. Stem Cells International. 2019(18),1-15.
11. Borrelli A., Tornesello A.L., Tornesello M.L., Buonaguro F.M., 2018. Cell penetrating peptides as molecular carriers for anti-cancer agents. Molecules. 23(2), 295.
12. Gan B.K., Yong C., Ho K.L., Omar A.R., Alitheen N.B., Tan W.S., 2018. Targeted delivery of cell penetrating peptide virus-like nanoparticles to skin cancer cells. Scientific Reports. 8(1), 8499.
13. He G.Z., Lin W.J., 2021. Peptide-functionalized nanoparticles-encapsulated cyclin-dependent kinases inhibitor seliciclib in transferrin receptor overexpressed cancer cells. Nanomaterials. 11(3), 772.
14. Deshpande P., Jhaveri A., Pattni B., Biswas S., Torchilin V., 2018. Transferrin and octaarginine modified dual-functional liposomes with improved cancer cell targeting and enhanced intracellular delivery for the treatment of ovarian cancer. Drug Delivery. 25(1), 517-532.
15. Liu Y., Mei L., Xu C., Yu Q., Shi K., Zhang L., Wang Y., Zhang Q., Gao H., Zhang Z., 2016. Dual receptor recognizing cell penetrating peptide for selective targeting, efficient intratumoral diffusion and synthesized anti-glioma therapy. Theranostics. 6(2), 177.
16. Bjorge J.D., Pang A., Fujita D.J., 2017. Delivery of gene targeting siRNAs to breast cancer cells using a multifunctional peptide complex that promotes both targeted delivery and endosomal release. PLoS One. 12(6), e0180578.
17. Lin W., Xie X., Deng J., Liu H., Chen Y., Fu X., Liu H., Yang Y., 2016. Cell-penetrating peptide-doxorubicin conjugate loaded NGR-modified nanobubbles for ultrasound triggered drug delivery. Journal of Drug Targeting. 24(2), 134-146.
18. Yang Y., Yang Y., Xie X., Cai X., Zhang H., Gong W., Wang Z., Mei X., 2014. PEGylated liposomes with NGR ligand and heat-activable cell-penetrating peptide–doxorubicin conjugate for tumor-specific therapy. Biomaterials. 35(14), 4368-4381.
19. Dana H., Chalbatani G.M., Mahmoodzadeh H., Karimloo R., Rezaiean O., Moradzadeh A., Mehmandoost N., Moazzen F., Mazraeh A., Marmari V., 2017. Molecular mechanisms and biological functions of siRNA. International Journal of Biomedical Science: IJBS. 13(2), 48.
20. Cantini L., Attaway C.C., Butler B., Andino L.M., Sokolosky M.L., Jakymiw A., 2013. Fusogenic-oligoarginine peptide-mediated delivery of siRNAs targeting the CIP2A oncogene into oral cancer cells. PLoS One. 8(9), e73348.
21. Alexander-Bryant A.A., Dumitriu A., Attaway C.C., Yu H., Jakymiw A., 2015. Fusogenic-oligoarginine peptide-mediated silencing of the CIP2A oncogene suppresses oral cancer tumor growth in vivo. Journal of Controlled Release. 218, 72-81.
22. Alexander-Bryant A.A., Zhang H., Attaway C.C., Pugh W., Eggart L., Sansevere R.M., Andino L.M., Dinh L., Cantini L.P., Jakymiw A., 2017. Dual peptide-mediated targeted delivery of bioactive siRNAs to oral cancer cells in vivo. Oral Oncology. 72, 123-131.
23. Ruan W., Zhai Y., Yu K., Wu C., Xu Y., 2018. Coated microneedles mediated intradermal delivery of octaarginine/BRAF siRNA nanocomplexes for anti-melanoma treatment. International Journal of Pharmaceutics. 553(1-2), 298-309.
24. Suh J.S., Lee H.J., Nam H., Jo B.S., Lee D.W., Kim J.H., Lee J. ., Chung C.P., Lee G., Park Y.J., 2017. Control of cancer stem cell like population by intracellular target identification followed by the treatment with peptide-siRNA complex. Biochemical and Biophysical Research Communications. 491(3), 827-833.
25. Lee Y.W., Hwang Y.E., Lee J.Y., Sohn J.H., Sung B.H., Kim S.C., 2018. VEGF siRNA delivery by a cancer-specific cell-penetrating peptide. Journal of Microbiology and Biotechnology. 28(3), 367-374.
26. Al‐Husaini K., Elkamel E., Han X., Chen P., 2020. Therapeutic potential of a cell penetrating peptide (CPP, NP1) mediated siRNA delivery: Evidence in 3D spheroids of colon cancer cells. The Canadian Journal of Chemical Engineering. 98(6), 1240-1254.
27. Morais C.M., Cardoso A.M., Cunha P.P., Aguiar L., Vale N., Lage E., Pinheiro M., Nunes C., Gomes P., Reis S., 2018. Acylation of the S413-PV cell-penetrating peptide as a means of enhancing its capacity to mediate nucleic acid delivery: Relevance of peptide/lipid interactions. Biochimica et Biophysica Acta (BBA)-Biomembranes. 1860(12), 2619-2634.
28. Freire J.M., de Figueiredo I.R., Valle J., Veiga A.S., Andreu D., Enguita F.J., Castanho M.A., 2017. siRNA-cell-penetrating peptides complexes as a combinatorial therapy against chronic myeloid leukemia using BV173 cell line as model. Journal of Controlled Release. 245, 127-136.
29. Di Fusco D., Dinallo V., Marafini I., Figliuzzi M. M., Romano B., Monteleone G., 2019. Antisense oligonucleotide: basic concepts and therapeutic application in inflammatory bowel disease. Frontiers in Pharmacology. 10, 305.
30. Gabriely G., Wurdinger T., Kesari S., Esau C.C., Burchard J., Linsley P.S., Krichevsky A.M., 2008. MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Molecular and Cellular Biology. 28(17), 5369-5380.
31. Zhang Y., Köllmer M., Buhrman J.S., Tang M.Y., Gemeinhart R.A., 2014. Arginine-rich, cell penetrating peptide–anti-microRNA complexes decrease glioblastoma migration potential. Peptides. 58, 83-90.
32. Song H., Oh B., Choi M., Oh J., Lee M., 2015. Delivery of anti-microRNA-21 antisense-oligodeoxynucleotide using amphiphilic peptides for glioblastoma gene therapy. Journal of Drug Targeting. 23(4), 360-370.
33. Oh B., Song H., Lee D., Oh J., Kim G., Ihm S.H., Lee M., 2017. Anti-cancer effect of R3V6 peptide-mediated delivery of an anti-microRNA-21 antisense-oligodeoxynucleotide in a glioblastoma animal model. Journal of Drug Targeting. 25(2), 132-139.
34. Yang S., Wang D., Sun Y., Zheng B., 2019. Delivery of antisense oligonucleotide using polyethylenimine-based lipid nanoparticle modified with cell penetrating peptide. Drug Delivery. 26(1), 965-974.
35. Zhao B.S., Roundtree I.A., He C., 2017. Post-transcriptional gene regulation by mRNA modifications. Nature reviews Molecular Cell Biology. 18(1), 31-42.
36. Palanikumar L., Al-Hosani S., Kalmouni M., Saleh H.O., Magzoub M., 2020. Hexokinase II-derived cell-penetrating peptide mediates delivery of microRNA mimic for cancer-selective cytotoxicity. Biochemistry. 59(24), 2259-2273.
37. Wu Y., Tang Y., Xie S., Zheng X., Zhang S., Mao J., Wang B., Hou Y., Hu L., Chai K., 2020. Chimeric peptide supramolecular nanoparticles for plectin-1 targeted miRNA-9 delivery in pancreatic cancer. Theranostics. 10(3), 1151.
38. Chen W., Zhou Y., Zhi X., Ma T., Liu H., Chen B. W., Zheng X., Xie S., Zhao B., Feng X., 2019. Delivery of miR-212 by chimeric peptide-condensed supramolecular nanoparticles enhances the sensitivity of pancreatic ductal adenocarcinoma to doxorubicin. Biomaterials. 192, 590-600.
39. Künnapuu K., Veiman K.L., Porosk L., Rammul E., Kiisholts K., Langel Ü., Kurrikoff K., 2019. Tumor gene therapy by systemic delivery of plasmid DNA with cell‐penetrating peptides. Faseb Bioadvances. 1(2), 105.
40. Hwang E., Riese 2nd D., Settleman J., Nilson L., Honig J., Flynn S., DiMaio D., 1993. Inhibition of cervical carcinoma cell line proliferation by the introduction of a bovine papillomavirus regulatory gene. Journal of Virology. 67(7), 3720-3729.
41. Apte A., Koren E., Koshkaryev A., Torchilin V.P., 2014. Doxorubicin in TAT peptide-modified multifunctional immunoliposomes demonstrates increased activity against both drug-sensitive and drug-resistant ovarian cancer models. Cancer Biology & Therapy. 15(1), 69-80.
42. LeCher J.C., Didier H.L., Dickson R.L., Slaughter L.R., Bejarano J.C., Ho S., Nowak S.J., Chrestensen C.A., McMurry J.L., 2023. Utilization of a cell-penetrating peptide-adaptor for delivery of human papillomavirus protein E2 into cervical cancer cells to arrest cell growth and promote cell death. Cancer Reports. 6(7), e1810.
43. Vivès E., Schmidt J., Pèlegrin A., 2008. Cell-penetrating and cell-targeting peptides in drug delivery. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 1786(2), 126-138.
44. Ryu J.S., Kratz F., Raucher D., 2021. Cell-penetrating doxorubicin released from elastin-like polypeptide kills doxorubicin-resistant cancer cells in in vitro study. International Journal of Molecular Sciences. 22(3), 1126.
45. Nasrolahi Shirazi A., Tiwari R., Chhikara B.S., Mandal D., Parang K., 2013. Design and biological evaluation of cell-penetrating peptide–doxorubicin conjugates as prodrugs. Molecular Pharmaceutics. 10(2), 488-499.
46. Gessner I., Neundorf I., 2020. Nanoparticles modified with cell-penetrating peptides: Conjugation mechanisms, physicochemical properties, and application in cancer diagnosis and therapy. International Journal of Molecular Sciences. 21(7), 2536.
47. Tseng Y.L., Liu J.J., Hong R.L., 2002. Translocation of liposomes into cancer cells by cell-penetrating peptides penetratin and tat: a kinetic and efficacy study. Molecular Pharmacology. 62(4), 864-872.
48. Ding Y., Cui W., Sun D., Wang G.-L., Hei Y., Meng S., Chen J.H., Xie Y., Wang Z.Q., 2017. In vivo study of doxorubicin-loaded cell-penetrating peptide-modified pH-sensitive liposomes: biocompatibility, bio-distribution, and pharmacodynamics in BALB/c nude mice bearing human breast tumors. Drug Design, Development and Therapy. 3105-3117.
49. Maeda H., Nakamura H., Fang J., 2013. The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Advanced Drug Delivery Reviews. 65(1), 71-79.
50. Maeda H., 2015. Toward a full understanding of the EPR effect in primary and metastatic tumors as well as issues related to its heterogeneity. Advanced Drug Delivery Reviews. 91, 3-6.
51. Xiang Y., Shan W., Huang Y., 2018. Improved anticancer efficacy of doxorubicin mediated by human-derived cell-penetrating peptide dNP2. International Journal of Pharmaceutics. 551(1-2), 14-22.
52. Xiang B., Jia X.L., Qi J.L., Yang L.P., Sun W.H., Yan X., Yang S.K., Cao D.Y., Du Q., Qi X.R., 2017. Enhancing siRNA-based cancer therapy using a new pH-responsive activatable cell-penetrating peptide-modified liposomal system. International Journal of Nanomedicine. 2385-2405.
53. Zhang X., Lin C., Lu A., Lin G., Chen H., Liu Q., Yang Z., Zhang H., 2017. Liposomes equipped with cell penetrating peptide BR2 enhances chemotherapeutic effects of cantharidin against hepatocellular carcinoma. Drug Delivery. 24(1), 986-998.
54. Lulla R.R., Goldman S., Yamada T., Beattie C.W., Bressler L., Pacini M., Pollack I.F., Fisher P.G., Packer R.J., Dunkel I.J., 2016. Phase I trial of p28 (NSC745104), a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in pediatric patients with recurrent or progressive central nervous system tumors: A Pediatric Brain Tumor Consortium Study. Neuro-oncology. 18(9), 1319-1325.
55. Warso M., Richards J., Mehta D., Christov K., Schaeffer C., Rae Bressler L., Yamada T., Majumdar D., Kennedy S., Beattie C., 2013. A first-in-class, first-in-human, phase I trial of p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in patients with advanced solid tumours. British Journal of Cancer. 108(5), 1061-1070.
56. Jin E., Zhang B., Sun X., Zhou Z., Ma X., Sun Q., Tang J., Shen Y., Van Kirk E., Murdoch W. J., 2013. Acid-active cell-penetrating peptides for in vivo tumor-targeted drug delivery. Journal of the American Chemical Society. 135(2), 933-940.
57. Guo F., Fu Q., Zhou K., Jin C., Wu W., Ji X., Yan Q., Yang Q., Wu D., Li A., 2020. Matrix metalloprotein-triggered, cell penetrating peptide-modified star-shaped nanoparticles for tumor targeting and cancer therapy. Journal of Nanobiotechnology. 18(1), 1-16.
58. Gao H., Zhang S., Cao S., Yang Z., Pang Z., Jiang X., 2014. Angiopep-2 and activatable cell-penetrating peptide dual-functionalized nanoparticles for systemic glioma-targeting delivery. Molecular Pharmaceutics. 11(8), 2755-2763.
59. Yuan B., Zhao Y., Dong S., Sun Y., Hao F., Xie J., Teng L., Lee R. J., Fu Y., Bi Y., 2019. Cell-penetrating peptide-coated liposomes for drug delivery across the blood–brain barrier. Anticancer Research. 39(1), 237-243.
60. Xiang B., Dong D.W., Shi N.Q., Gao W., Yang Z.Z., Cui Y., Cao D.Y., Qi X.R., 2013. PSA-responsive and PSMA-mediated multifunctional liposomes for targeted therapy of prostate cancer. Biomaterials. 34(28), 6976-6991.
61. Crombez L., Morris M. C., Dufort S., Aldrian-Herrada G., Nguyen Q., Mc Master G., Coll J.L., Heitz F., Divita G., 2009. Targeting cyclin B1 through peptide-based delivery of siRNA prevents tumour growth. Nucleic Acids Research. 37(14), 4559-4569.
62. Lo J.H., Hao L., Muzumdar M.D., Raghavan S., Kwon E.J., Pulver E.M., Hsu F., Aguirre A.J., Wolpin B.M., Fuchs C.S., 2018. iRGD-guided tumor-penetrating nanocomplexes for therapeutic siRNA delivery to pancreatic cancer. Molecular Cancer Therapeutics. 17(11), 2377-2388.
63. Michiue H., Eguchi A., Scadeng M., Dowdy S. F., 2009. Induction of in vivo synthetic lethal RNAi responses to treat glioblastoma. Cancer Biology & Therapy. 8(23), 2304-2311.
64. Shin M.C., Zhang J., Min K.A., Lee K., Moon C., Balthasar J.P., Yang V.C., 2014. Combination of antibody targeting and PTD-mediated intracellular toxin delivery for colorectal cancer therapy. Journal of Controlled Release. 194, 197-210.
65. Moktan S., Perkins E., Kratz F., Raucher D., 2012. Thermal targeting of an acid-sensitive doxorubicin conjugate of elastin-like polypeptide enhances the therapeutic efficacy compared with the parent compound in vivo. Molecular Cancer Therapeutics. 11(7), 1547-1556.
66. Zhang Q., Wang J., Zhang H., Liu D., Ming L., Liu L., Dong Y., Jian B., Cai D., 2018. The anticancer efficacy of paclitaxel liposomes modified with low-toxicity hydrophobic cell-penetrating peptides in breast cancer: an in vitro and in vivo evaluation. RSC Advances, 8(43), 24084-24093.
67. Xie X., Lin W., Li M., Yang Y., Deng J., Liu H., Chen Y., Fu X., Liu H., Yang Y., 2016. Efficient siRNA delivery using novel cell-penetrating peptide-siRNA conjugate-loaded nanobubbles and ultrasound. Ultrasound in Medicine & Biology. 42(6), 1362-1374.
