Approaches and materials for endocytosis-independent intracellular delivery of proteins

Chen, Nanxi; Zang, Mingming; Zhang, Youxi; Lü, Hong‐Yan; Zhao, Qinfu; Wang, Siling; Gao, Yikun

doi:10.1016/j.biomaterials.2022.121567

Cited by 31 publications

(26 citation statements)

References 214 publications

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“…According to the literature, the endocytosis mechanisms can be classified as phagocytosis, pinocytosis, and receptor‐mediated endocytosis. [ 24 ] The internalization of nanoparticles mainly depends on receptor‐mediated endocytosis, which includes clathrin/caveolae‐mediated endocytosis, and clathrin/caveolae‐independent endocytosis. [ 25 ] The endocytosis mechanism of OGP‐tFNAs was explored accordingly.…”

Section: Resultsmentioning

confidence: 99%

Myelosuppression Alleviation and Hematopoietic Regeneration by Tetrahedral‐Framework Nucleic‐Acid Nanostructures Functionalized with Osteogenic Growth Peptide

et al. 2022

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As major complications of chemoradiotherapy, myelosuppression and hematopoietic-system damage severely affect immunologic function and can delay or even terminate treatment for cancer patients. Although several specific cytokines have been used for hematopoiesis recovery, their effect is limited, and they may increase the risk of tumor recurrence. In this study, osteogenic growth peptide functionalized tetrahedral framework nucleic-acid nanostructures (OGP-tFNAs) are prepared; they combine the positive hematopoiesis stimulating effect of OGP and the drug carrying function of tFNAs. The potential of OGP-tFNAs for hematopoietic stimulation and microenvironment regulation is investigated. It is shown that OGP-tFNAs can protect bone marrow stromal cells from 5-fluorouracil (5-FU)-induced DNA damage and apoptosis. OGP-tFNAs pretreatment activates the extracellularly regulated protein kinase signal and downregulates apoptosis-related proteins. OGP-tFNAs also alleviate the chemotherapy-induced inhibition of hematopoiesis-related cytokine expression, which is crucial for hematopoiesis reconstitution. In conclusion, OGP-tFNAs can protect hematopoietic cells and their microenvironment from chemotherapy-induced injuries and myelosuppression, while promoting hematopoiesis regeneration.

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Section: Resultsmentioning

confidence: 99%

Myelosuppression Alleviation and Hematopoietic Regeneration by Tetrahedral‐Framework Nucleic‐Acid Nanostructures Functionalized with Osteogenic Growth Peptide

et al. 2022

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“…An ideal intracellular delivery system should include the following features: (1) efficient delivery and successful release of the cargo inside the cell; (2) minimal or no influence on the cargo activities; (3) minimal cell perturbation; (4) potential for cell-selective and/or subcellular-targeted delivery (i.e., to the cytosol, nucleus, or other specific organelles). A plethora of approaches are now being explored to facilitate the cellular uptake of proteins, including physical methods (Figure b, c), direct protein modifications (Figure d), and carrier-mediated delivery systems (Figure e). ,,− …”

Section: How Can We Deliver Antibodies Into Cells?mentioning

confidence: 99%

“…612 Some controversial studies have even revealed that CPPs crossed the membrane via both endocytotic and nonendocytotic pathways depending on various factors such as CPP-cargo combination, the concentration and molecular weight of the cargo, and others. 576,613 At present, cationic, amphiphilic, and hydrophobic CPPs have been developed for intracellular delivery. A growing number of peptides, when used alone or in conjugation with other CPPs, also showed good promise in organelle-targeted delivery of biologics.…”

Section: Cell-penetrating Peptides (Cpps)mentioning

confidence: 99%

The Dawn of a New Era: Targeting the “Undruggables” with Antibody-Based Therapeutics

et al. 2023

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The high selectivity and affinity of antibodies toward their antigens have made them a highly valuable tool in disease therapy, diagnosis, and basic research. A plethora of chemical and genetic approaches have been devised to make antibodies accessible to more “undruggable” targets and equipped with new functions of illustrating or regulating biological processes more precisely. In this Review, in addition to introducing how naked antibodies and various antibody conjugates (such as antibody-drug conjugates, antibody-oligonucleotide conjugates, antibody-enzyme conjugates, etc.) work in therapeutic applications, special attention has been paid to how chemistry tools have helped to optimize the therapeutic outcome (i.e., with enhanced efficacy and reduced side effects) or facilitate the multifunctionalization of antibodies, with a focus on emerging fields such as targeted protein degradation, real-time live-cell imaging, catalytic labeling or decaging with spatiotemporal control as well as the engagement of antibodies inside cells. With advances in modern chemistry and biotechnology, well-designed antibodies and their derivatives via size miniaturization or multifunctionalization together with efficient delivery systems have emerged, which have gradually improved our understanding of important biological processes and paved the way to pursue novel targets for potential treatments of various diseases.

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“…It stands for 1 ) the emergence of cell‐penetrating activity in a substrate appended with a dynamic covalent cascade exchanger (CAX), and 2 ) the inhibition of this cell penetration with thiol‐reactive agents, often also by the same CAX. Since the introduction of cell‐penetrating poly(disulfide)s to thiol‐mediated uptake in 2014, [2] various CAXs have been explored to deliver a wide variety of substrates to the cytosol, [3–17] including challenging objects like quantum dots, [17] genes [7–11] or proteins, [6,16] from antibodies [6] to genome editing machinery, also in vivo [7] . Although weak and unreliable, [18] the uptake inhibition with Ellman ’s reagent has traditionally been accepted as experimental evidence for the occurrence of thiol‐mediated uptake [19–21] .…”

Section: Introductionmentioning

confidence: 99%

Tetrel‐Centered Exchange Cascades to Decouple Inhibition and Induction of Thiol‐Mediated Uptake: Introducing Cell‐Penetrating Thiolactones, Focus on Reversible Michael Acceptor Dimers

Lim

Sakai

Matile

2023

Helvetica Chimica Acta

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This study adds thiolactones to the collection of cascade exchangers (CAXs) and reports with dynamic covalent Michael acceptor dimers the first CAXs that rather inhibit than enable thiol‐mediated uptake. The superior performance of dimers compared to monomeric Michael acceptors as inhibitors might suggest that top inhibitors move along thiol/ate arrays without losing covalent contact, while cell penetrators exchange along disulfide arrays. This decoupling of inhibition and induction of thiol‐mediated uptake is important because the latter is promising for drug delivery, while the former possibly helps to reveal targets associated with antiviral, antithrombotic and antitumor activity, leading to drug discovery. These results are consistent with the working model of thiol‐mediated uptake as a general complex network in charge of bringing matter into cells, and thus support its validity.

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Approaches and materials for endocytosis-independent intracellular delivery of proteins

Cited by 31 publications

References 214 publications

Myelosuppression Alleviation and Hematopoietic Regeneration by Tetrahedral‐Framework Nucleic‐Acid Nanostructures Functionalized with Osteogenic Growth Peptide

Myelosuppression Alleviation and Hematopoietic Regeneration by Tetrahedral‐Framework Nucleic‐Acid Nanostructures Functionalized with Osteogenic Growth Peptide

The Dawn of a New Era: Targeting the “Undruggables” with Antibody-Based Therapeutics

Tetrel‐Centered Exchange Cascades to Decouple Inhibition and Induction of Thiol‐Mediated Uptake: Introducing Cell‐Penetrating Thiolactones, Focus on Reversible Michael Acceptor Dimers

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