In the field of nanotherapeutics, gaining cellular entry into the cytoplasm of the target cell continues to be an ultimate challenge. There are many physicochemical factors such as charge, size and molecular weight of the molecules and delivery vehicles, which restrict their cellular entry. Hence, to dodge such situations, a class of short peptides called cell-penetrating peptides (CPPs) was brought into use. CPPs can effectively interact with the cell membrane and can assist in achieving the desired intracellular entry. Such strategy is majorly employed in the field of cancer therapy and diagnosis, but now it is also used for other purposes such as evaluation of atherosclerotic plaques, determination of thrombin levels and HIV therapy. Thus, the current review expounds on each of these mentioned aspects. Further, the review briefly summarizes the basic know-how of CPPs, their utility as therapeutic molecules, their use in cancer therapy, tumor imaging and their assistance to nanocarriers in improving their membrane penetrability. The review also discusses the challenges faced with CPPs pertaining to their stability and also mentions the strategies to overcome them. Thus, in a nutshell, this review will assist in understanding how CPPs can present novel possibilities for resolving the conventional issues faced with the present-day nanotherapeutics.
Futaki S, Nakase I. Futaki S, et al. Acc Chem Res. 2017 Oct 17;50(10):2449-2456. doi: 10.1021/acs.accounts.7b00221. Epub 2017 Sep 14. Acc Chem Res. 2017. PMID: 28910080
Park SE, Sajid MI, Parang K, Tiwari RK. Park SE, et al. Mol Pharm. 2019 Sep 3;16(9):3727-3743. doi: 10.1021/acs.molpharmaceut.9b00633. Epub 2019 Aug 8. Mol Pharm. 2019. PMID: 31329448 Review.
Shi NQ, Qi XR, Xiang B, Zhang Y. Shi NQ, et al. J Control Release. 2014 Nov 28;194:53-70. doi: 10.1016/j.jconrel.2014.08.014. Epub 2014 Aug 23. J Control Release. 2014. PMID: 25151981 Review.
Choi YS, Lee JY, Suh JS, Lee SJ, Yang VC, Chung CP, Park YJ. Choi YS, et al. Curr Pharm Biotechnol. 2011 Aug;12(8):1166-82. doi: 10.2174/138920111796117391. Curr Pharm Biotechnol. 2011. PMID: 21470141 Review.
Böhmová E, Machová D, Pechar M, Pola R, Venclíková K, Janoušková O, Etrych T. Böhmová E, et al. Physiol Res. 2018 Oct 30;67(Suppl 2):S267-S279. doi: 10.33549/physiolres.933975. Physiol Res. 2018. PMID: 30379549 Review.
Kumar M, Kumar D, Kumar D, Garg Y, Chopra S, Bhatia A. Kumar M, et al. AAPS PharmSciTech. 2024 May 10;25(5):108. doi: 10.1208/s12249-024-02827-5. AAPS PharmSciTech. 2024. PMID: 38730090 Review.
Aschmann D, Knol RA, Kros A. Aschmann D, et al. Acc Chem Res. 2024 Apr 16;57(8):1098-1110. doi: 10.1021/acs.accounts.3c00769. Epub 2024 Mar 26. Acc Chem Res. 2024. PMID: 38530194 Free PMC article.
Matsuura K, Inaba H. Matsuura K, et al. Biophys Rev (Melville). 2023 Dec 18;4(4):041303. doi: 10.1063/5.0179171. eCollection 2023 Dec. Biophys Rev (Melville). 2023. PMID: 38505425 Free PMC article. Review.
Agiba AM, Arreola-Ramírez JL, Carbajal V, Segura-Medina P. Agiba AM, et al. Molecules. 2024 Jan 30;29(3):636. doi: 10.3390/molecules29030636. Molecules. 2024. PMID: 38338380 Free PMC article. Review.
Pang H, Wu Y, Chen Y, Chen C, Nie X, Li P, Huang G, Xu ZP, Han FY. Pang H, et al. Drug Deliv Transl Res. 2024 Sep;14(9):2345-2355. doi: 10.1007/s13346-023-01504-7. Epub 2024 Jan 12. Drug Deliv Transl Res. 2024. PMID: 38214820 Free PMC article.