Interdependence of charge and secondary structure on cellular uptake of cell penetrating peptide functionalized silica nanoparticles

Gessner, Isabel; Klimpel, Annika; Klußmann, Merlin; Neundorf, Ines; Mathur, Sanjay

doi:10.1039/c9na00693a

Cited by 24 publications

(22 citation statements)

References 38 publications

(53 reference statements)

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“…Moreover, our group has recently investigated the internalization efficiency of CPP-NP conjugates based on the electrostatic interactions of silica particles and sC18 [56]. The presence of deprotonated hydroxyl functionalities on the surface of silica particles at neutral pH allowed for simple self-assembly of positively charged CPPs on the NP surface, which resulted in strongly positively charged CPP-silica conjugates.…”

Section: Non-covalent Attachmentmentioning

confidence: 99%

“…In the case of amphipathic CPPs, such as MAP, the N-terminal tail plays a significant role for the NP adsorption. Therefore, slight changes in peptide sequences that alter their net charge have a significant influence on their binding affinity and can, for example, be used to control the density of CPPs on negatively charged NP surfaces [56]. Moreover, the number and order of amino acids in the peptide sequence, especially charged ones, have a significant effect on their internalization efficiency, also when conjugated to NPs.…”

Section: Influence Of Charge On Cpp-np Conjugate Formationmentioning

confidence: 99%

“…Nevertheless, the chemical interaction between functional groups of the peptide and those of the NPs can have a significant influence on the formation of the secondary structure. CD spectroscopy studies of sC18-silica conjugates have demonstrated the formation of a less pronounced alpha-helical structure compared to the free CPPs, even though a noncovalent approach has been used for the conjugate formation [56]. The multiple hydrogen bond formation between cationic amino acids and deprotonated surface silanol groups presumably has led to reduced flexibility of the CPP backbone upon conjugation, which impairs the full development of an alpha helix.…”

Section: Influence Of Carrier On Cpp-np Conjugate Formationmentioning

confidence: 99%

“…On the other hand, cation-rich CPPs that possess a high positive net charge have demonstrated low toxicity even at concentrations of 100 µM, although the attachment of cargo has shown to have a significant influence on the cytotoxicity for some CPPs [83]. Nevertheless, in most reported cases, no increase in cytotoxicity was observed when CPPs were combined with NPs [56,78,84,85]. Only a few examples, for instance, by Liu and co-workers, demonstrated that the concentration of attached CPP, in this case, R9, which was linked to the fusogenic peptide INF7, to CdSe/ZnS quantum dots (QDs) dramatically changed the observed cytotoxicity on A549 cells [86].…”

Section: Influence Of Cpp-np Conjugate Formation On Toxicity Biocompmentioning

confidence: 99%

See 3 more Smart Citations

Nanoparticles Modified with Cell-Penetrating Peptides: Conjugation Mechanisms, Physicochemical Properties, and Application in Cancer Diagnosis and Therapy

Gessner

Neundorf

2020

IJMS

Self Cite

144

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Based on their tunable physicochemical properties and the possibility of producing cell-specific platforms through surface modification with functional biomolecules, nanoparticles (NPs) represent highly promising tools for biomedical applications. To improve their potential under physiological conditions and to enhance their cellular uptake, combinations with cell-penetrating peptides (CPPs) represent a valuable strategy. CPPs are often cationic peptide sequences that are able to translocate across biological membranes and to carry attached cargos inside cells and have thus been recognized as versatile tools for drug delivery. Nevertheless, the conjugation of CPP to NP surfaces is dependent on many properties from both individual components, and further insight into this complex interplay is needed to allow for the fabrication of highly stable but functional vectors. Since CPPs per se are nonselective and enter nearly all cells likewise, additional decoration of NPs with homing devices, such as tumor-homing peptides, enables the design of multifunctional platforms for the targeted delivery of chemotherapeutic drugs. In this review, we have updated the recent advances in the field of CPP-NPs, focusing on synthesis strategies, elucidating the influence of different physicochemical properties, as well as their application in cancer research.

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Section: Non-covalent Attachmentmentioning

confidence: 99%

Section: Influence Of Charge On Cpp-np Conjugate Formationmentioning

confidence: 99%

Section: Influence Of Carrier On Cpp-np Conjugate Formationmentioning

confidence: 99%

Section: Influence Of Cpp-np Conjugate Formation On Toxicity Biocompmentioning

confidence: 99%

See 2 more Smart Citations

Nanoparticles Modified with Cell-Penetrating Peptides: Conjugation Mechanisms, Physicochemical Properties, and Application in Cancer Diagnosis and Therapy

Gessner

Neundorf

2020

IJMS

Self Cite

144

View full text Add to dashboard Cite

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“…The authors linked this to the possible degradation of the peptide layer of CPP-CSUn nanoparticles by luminal enzymes in the rat GIT, or the different nature of the mucus barrier of the in vivo model compared to the in vitro cell model [ 104 ]. The surface functionalisation is an interesting approach commonly used to facilitate the cellular internalisation of the silica nanoparticles and enhance their delivery efficiency [ 105 , 106 , 107 , 108 ].…”

Section: Applications Of Silica Nanoparticles In Transmucosal Drugmentioning

confidence: 99%

Silica Nanoparticles in Transmucosal Drug Delivery

Ways

Lau

et al. 2020

Pharmaceutics

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Transmucosal drug delivery includes the administration of drugs via various mucous membranes, such as gastrointestinal, nasal, ocular, and vaginal mucosa. The use of nanoparticles in transmucosal drug delivery has several advantages, including the protection of drugs against the harsh environment of the mucosal lumens and surfaces, increased drug residence time, and enhanced drug absorption. Due to their relatively simple synthetic methods for preparation, safety profile, and possibilities of surface functionalisation, silica nanoparticles are highly promising for transmucosal drug delivery. This review provides a description of silica nanoparticles and outlines the preparation methods for various core and surface-functionalised silica nanoparticles. The relationship between the functionalities of silica nanoparticles and their interactions with various mucous membranes are critically analysed. Applications of silica nanoparticles in transmucosal drug delivery are also discussed.

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Bioinert, Stealth or Interactive: How Surface Chemistry of Nanocarriers Determines Their Fate In Vivo

Friedl

Nele

Rosa

et al. 2021

Adv Funct Materials

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Nanocarriers (NCs) have emerged as powerful tools to improve drug solubility, to promote drug transport across membranes, to protect their payload from premature degradation, and to deliver drugs in a controlled and targeted manner. Their performance strongly depends on the surface chemistry, which governs their interaction with the biological environment. Bioinert and stealth surface features are advantageous to avoid unintended interactions with endogenous surfaces at off‐target sites and with the immune system, whereas at the target site these carriers should be highly interactive guaranteeing intracellular delivery of their payload. These key surface properties—bioinert and stealth versus interactive at the target site—are in contradiction to each other so that the best compromise between them has to be found. Alternatively, surface structures interacting preferentially with the membrane of target cells can be utilized. Stimuli‐responsive surfaces able to convert from bioinert and stealth to interactive at the target site have been recently introduced. A deepened understanding of how these different approaches influence the performance of NCs in the body is of particular importance in order to improve their efficacy. This review focuses on the surface chemistry of NCs providing the best compromise between bioinert and stealth versus interactive features.

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Interdependence of charge and secondary structure on cellular uptake of cell penetrating peptide functionalized silica nanoparticles

Abstract: The capability of cell-penetrating peptides (CPPs) to enable translocation of cargos across biological barriers shows promising pharmaceutical potential for the transport of drug molecules, as well as nanomaterials, into cells.

Cited by 24 publications

References 38 publications

Nanoparticles Modified with Cell-Penetrating Peptides: Conjugation Mechanisms, Physicochemical Properties, and Application in Cancer Diagnosis and Therapy

Nanoparticles Modified with Cell-Penetrating Peptides: Conjugation Mechanisms, Physicochemical Properties, and Application in Cancer Diagnosis and Therapy

Silica Nanoparticles in Transmucosal Drug Delivery

Bioinert, Stealth or Interactive: How Surface Chemistry of Nanocarriers Determines Their Fate In Vivo

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