Cell-penetrating peptide together with PEG-modified mesostructured silica nanoparticles promotes mucous permeation and oral delivery of therapeutic proteins and peptides

Tan, Xinyi; Zhang, Yan; Wang, Qian; Ren, Tianyang; Gou, Jingxin; Guo, Wei; Yin, Tian; He, Huan; Zhang, Yu; Tang, Xing

doi:10.1039/c9bm00274j

Cited by 52 publications

(32 citation statements)

References 36 publications

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“…In this respect, Tan et al recently presented CPP-PEG-modified mesostructured silica NPs that greatly enhanced the bioavailability of therapeutic peptides and proteins. Significantly promoted mucous permeation and oral availability of drug payloads were observed and demonstrated the potential of their study for future developments in this direction [55].…”

Section: Current State-of-the-art and Future Perspectivesmentioning

confidence: 93%

“…To date, the often strong positive net charge of CPPs has been exploited for their self-assembly on the surface of negatively charged nanostructures. For instance, Tan and co-workers prepared mesoporous silica particles with strong negative zeta potential (−32 mV) and large pores up to 11 nm, which they used for the noncovalent loading with penetratin [55]. Lower loading rates of CPPs were observed after precedent surface modifications of silica particles with polyethylene glycol (PEG) (average molecular weight 4000 and 10,000, respectively), presumably related to the increase in zeta potential, as well as shielding effects of long PEG chains.…”

Section: Non-covalent Attachmentmentioning

confidence: 99%

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

Gessner

Neundorf

2020

IJMS

155

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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: Current State-of-the-art and Future Perspectivesmentioning

confidence: 93%

Section: Non-covalent Attachmentmentioning

confidence: 99%

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

Gessner

Neundorf

2020

IJMS

155

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“…ese molecules include cell penetrating peptide (CPP), avidin-biotin, saccharides, and transferrins [116][117][118]. Tan et al found that CPP mainly affects transport and exocytosis, whereas PEG polymer influences mucus penetration [119]. Approaches to overcome this limitation while still maintaining the advantages of PEG have been tested, such as preparing PEG covalently linked to 1,2dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE).…”

Section: Np Surface Coatings and Tumor Penetrationmentioning

confidence: 99%

Physical Properties of Nanoparticles That Result in Improved Cancer Targeting

Zein

Sharrouf

Selting

2020

Journal of Oncology

169

116

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The therapeutic efficacy of drugs is dependent upon the ability of a drug to reach its target, and drug penetration into tumors is limited by abnormal vasculature and high interstitial pressure. Chemotherapy is the most common systemic treatment for cancer but can cause undesirable adverse effects, including toxicity to the bone marrow and gastrointestinal system. Therefore, nanotechnology-based drug delivery systems have been developed to reduce the adverse effects of traditional chemotherapy by enhancing the penetration and selective drug retention in tumor tissues. A thorough knowledge of the physical properties (e.g., size, surface charge, shape, and mechanical strength) and chemical attributes of nanoparticles is crucial to facilitate the application of nanotechnology to biomedical applications. This review provides a summary of how the attributes of nanoparticles can be exploited to improve therapeutic efficacy. An ideal nanoparticle is proposed at the end of this review in order to guide future development of nanoparticles for improved drug targeting in vivo.

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“…We previously showed that these peptides, while engaging with different cellular receptors, invoke a similar macropinocytosis-like process for cell entry 19,26 . Besides assisting the NP uptake, these CPPs were also used to lead NPs from one cell to another 16,27 , and may help elucidate the function of ligand-receptor interactions during intercellular exchange.…”

Section: Resultsmentioning

confidence: 99%

Extracellular vesicles mediate the intercellular exchange of nanoparticles

Tang

Wei

et al. 2021

Preprint

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In order to exert their therapeutic effects, nanoparticles (NPs) often need to travel into the tissues composed of multilayered cells. Accumulative evidence has revealed the central role of transcellular transport route (entry into one cell, exocytosis, and re-entry into another) in this process. While NP endocytosis and subcellular transport have been intensively characterized, the exocytosis and re-entry steps are poorly understood, which becomes a barrier to improve NP delivery into complex tissues. Here, we termed the exocytosis and re-entry steps together as intercellular exchange. We developed a novel collagen-based 3D cellular assay to specifically monitor and quantify the intercellular exchange events of NPs and distinguish the contributions of several potential mechanisms. Our results showed that NPs can be exocytosed freely or enclosed inside extracellular vesicles (EVs) for re-entry, while direct cell-cell contact is hardly involved. EVs account for a significant fraction of NP intercellular exchange, and its importance in NP delivery was demonstrated in vitro and in vivo. Intriguingly, while freely released NPs engage with the same cellular receptors for re-entry, EV-enclosed ones bypass this dependence. These studies provide an easy and precise system to investigate the intercellular exchange stage of NP delivery, and shed the first light in the importance of EVs in NP transport between cells and across complex tissues.

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Cell-penetrating peptide together with PEG-modified mesostructured silica nanoparticles promotes mucous permeation and oral delivery of therapeutic proteins and peptides

Abstract: Electrostatic particle complexes, CPP/TPP/NP, consisting of PEG-modified silica NPs with TPP and CPP, showed satisfactory stability and mucous penetration.

Cited by 52 publications

References 36 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

Physical Properties of Nanoparticles That Result in Improved Cancer Targeting

Extracellular vesicles mediate the intercellular exchange of nanoparticles

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