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      Cell-penetrating peptides (CPPs): an overview of applications for improving the potential of nanotherapeutics

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          Abstract

          Restricted entry into the cells stands as an ultimate challenge for nanotherapeutics to exhibit their efficacy. Cell penetrating peptides can act as a crucial assistant for overcoming this challenge.

          Abstract

          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.

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          Most cited references335

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          Stimuli-responsive nanocarriers for drug delivery.

          Spurred by recent progress in materials chemistry and drug delivery, stimuli-responsive devices that deliver a drug in spatial-, temporal- and dosage-controlled fashions have become possible. Implementation of such devices requires the use of biocompatible materials that are susceptible to a specific physical incitement or that, in response to a specific stimulus, undergo a protonation, a hydrolytic cleavage or a (supra)molecular conformational change. In this Review, we discuss recent advances in the design of nanoscale stimuli-responsive systems that are able to control drug biodistribution in response to specific stimuli, either exogenous (variations in temperature, magnetic field, ultrasound intensity, light or electric pulses) or endogenous (changes in pH, enzyme concentration or redox gradients).
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            Regulated portals of entry into the cell.

            The plasma membrane is the interface between cells and their harsh environment. Uptake of nutrients and all communication among cells and between cells and their environment occurs through this interface. 'Endocytosis' encompasses several diverse mechanisms by which cells internalize macromolecules and particles into transport vesicles derived from the plasma membrane. It controls entry into the cell and has a crucial role in development, the immune response, neurotransmission, intercellular communication, signal transduction, and cellular and organismal homeostasis. As the complexity of molecular interactions governing endocytosis are revealed, it has become increasingly clear that it is tightly coordinated and coupled with overall cell physiology and thus, must be viewed in a broader context than simple vesicular trafficking.
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              Is Open Access

              In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus

              Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.
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                Author and article information

                Contributors
                Journal
                BSICCH
                Biomaterials Science
                Biomater. Sci.
                Royal Society of Chemistry (RSC)
                2047-4830
                2047-4849
                February 23 2021
                2021
                : 9
                : 4
                : 1153-1188
                Affiliations
                [1 ]Centre for Pharmaceutical Nanotechnology
                [2 ]Department of Pharmaceutics
                [3 ]National Institute of Pharmaceutical Education and Research (NIPER)
                [4 ]Punjab-160062
                [5 ]India
                Article
                10.1039/D0BM01755H
                33355322
                bb1cd3d7-a212-4463-84ac-96257aafcf17
                © 2021

                http://rsc.li/journals-terms-of-use

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