Disulfide Cleavable Linker
Disulfide cleavable linkers provide redox-responsive bonds for drug delivery because extracellular and intracellular glutathione gradients enable selective activation in reductive cytoplasmic environments[1]. Mechanistically, disulfide cleavage can release small-molecule drugs, macromolecule conjugates, or masked bioactive agents after cellular entry[2][3]. In cancer models, disulfide-containing prodrugs, nanoparticles, nanogels, vaccines, and aptamer-drug conjugates have improved controlled release, tumor-cell uptake, or antitumor response[2][4][5][6]. Compared with non-redox-responsive analogues, disulfide-linked systems showed faster drug release, stronger cellular uptake, or higher tumor-selective cytotoxicity in reported experimental models[4][7][8]. For research design, linker electronics, steric hindrance, substituent position, and biorelevant reducing agents such as glutathione should guide stability and cleavage-rate evaluation[2][9].
References:
- [1]. Deng Z, et al. Disulfide-Based Self-Immolative Linkers and Functional Bioconjugates for Biological Applications. Macromol Rapid Commun. 2020 Jan;41(1):e1900531. [Content Brief]
- [2]. Wang Q, et al. Disulfide based prodrugs for cancer therapy. RSC Adv. 2020 Jun 25;10(41):24397-24409. [Content Brief]
- [3]. Yang X, et al. Making smart drugs smarter: The importance of linker chemistry in targeted drug delivery. Med Res Rev. 2020 Nov;40(6):2682-2713. [Content Brief]
- [4]. Conte C, et al. Enhanced uptake in 2D- and 3D- lung cancer cell models of redox responsive PEGylated nanoparticles with sensitivity to reducing extra- and intracellular environments. J Control Release. 2018 May 10;277:126-141. [Content Brief]
- [5]. Kramer K, et al. Intracellular Cleavable CpG Oligodeoxynucleotide-Antigen Conjugate Enhances Anti-tumor Immunity. Mol Ther. 2017 Jan 4;25(1):62-70. [Content Brief]
- [6]. Wu Y, et al. Improvement of Drug Release from an Aptamer Drug Conjugate Using Reductive-sensitive Linkers for Tumor-targeted Drug Delivery. AAPS J. 2025 May 20;27(4):95. [Content Brief]
- [7]. Drude N, et al. Impact of Glutathione Modulation on Stability and Pharmacokinetic Profile of Redox-Sensitive Nanogels. Small. 2018 Apr;14(14):e1704093. [Content Brief]
- [8]. Ai X, et al. Star-shape redox-responsive PEG-sheddable copolymer of disulfide-linked polyethylene glycol-lysine-di-tocopherol succinate for tumor-triggering intracellular doxorubicin rapid release: head-to-head comparison. Macromol Biosci. 2014 Oct;14(10):1415-28. [Content Brief]
- [9]. Phillips DJ, et al. Redox-sensitive materials for drug delivery: targeting the correct intracellular environment, tuning release rates, and appropriate predictive systems. Antioxid Redox Signal. 2014 Aug 10;21(5):786-803. [Content Brief]
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Disulfide Cleavable Linker Related Products (124)
Related Products (124)
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Sulfo-SNPB
0 ImagesCat. No.: HY-129376CAS No.: 1193111-37-3Sulfo-SNPB is a cleavable linker that is used for making antibody-drug conjugate (ADC).
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PPC-NB
0 ImagesPPC-NB is a glutathione cleavable linker used for the antibody-drug conjugate (ADC).
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Tetrazine-SS-NHS
0 ImagesCat. No.: HY-136032CAS No.: 2739938-13-5Tetrazine-SS-NHS is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Tetrazine-SS-NHS is a click chemistry reagent, it contains a Tetrazine group that can undergo an inverse electron demand Diels-Alder reaction (iEDDA) with molecules containing TCO groups.
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PC SPDP-NHS carbonate ester
0 ImagesCat. No.: HY-140138CAS No.: 2279944-61-3PC SPDP-NHS carbonate ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Sulfo-LC-SPDP
0 ImagesCat. No.: HY-126495CAS No.: 150244-18-1Sulfo-LC-SPDP is a heterobifunctional, thiol-cleavable and membrane impermeable crosslinker.
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Azido-C2-SS-PEG2-C2-acid
0 ImagesAzido-C2-SS-PEG2-C2-acid is a cleavable 2 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-C2-SS-PEG2-C2-acid is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
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4-Methyl-4-(methyldisulfanyl)pentanoic acid
0 Images4-Methyl-4-(methyldisulfanyl)pentanoic acid is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Sulfo-SPP
0 ImagesCat. No.: HY-129377CAS No.: 452072-27-4Sulfo-SPP is a heterobifunctional, thiol-cleavable and membrane impermeable crosslinker.
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Acid-PEG2-SS-PEG2-acid
0 ImagesCat. No.: HY-140112CAS No.: 1807539-10-1Acid-PEG2-SS-PEG2-acid is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Azido-PEG3-SSPy
0 ImagesAzido-PEG3-SSPy is a cleavable 3 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Azido-PEG3-SSPy is a click chemistry reagent, it contains an Azide group and can undergo copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc) with molecules containing Alkyne groups. It can also undergo strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with molecules containing DBCO or BCN groups.
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SPDH
0 ImagesCat. No.: HY-129374CAS No.: 1824718-79-7SPDH is a cleavable ADC linker used for diagnosis and treatment of cancer or B cell proliferative diseas.
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PPA
0 ImagesPPA is an ADC linker (US20060073528A1). PPA can be used for making antibody-drug conjugate.
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Bis-Tos-(2-hydroxyethyl disulfide)
0 ImagesBis-Tos-(2-hydroxyethyl disulfide) is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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PDdEC-NB
0 ImagesCat. No.: HY-126519CAS No.: 1956318-90-3PDdEC-NB is a disulfide cleavable linker used for the antibody-drug conjugate (ADC).
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DBCO-SS-PEG4-Biotin
0 ImagesCat. No.: HY-135979DBCO-SS-PEG4-Biotin is a cleavable 4 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs). DBCO-SS-PEG4-Biotin is a click chemistry reagent, it contains a DBCO group that can undergo strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules containing Azide groups.
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SNPB-sulfo-Me
0 ImagesCat. No.: HY-129375CAS No.: 890409-86-6SNPB-sulfo-Me is a cleavable linker that is used for making antibody-drug conjugate (ADC).
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NO2-SPP
0 ImagesCat. No.: HY-129367CAS No.: 663598-61-6NO2-SPP is a cleavable linker that is used for making antibody-drug conjugate (ADC).
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m-PEG6-SS-PEG6-methyl
0 ImagesCat. No.: HY-140121CAS No.: 1007386-15-3m-PEG6-SS-PEG6-methyl is a cleavable 12 unit PEG ADC linker used in the synthesis of antibody-drug conjugates (ADCs).
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Methyltetrazine-SS-NHS
0 ImagesCat. No.: HY-136033CAS No.: 2740453-91-0Methyltetrazine-SS-NHS is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). Methyltetrazine-SS-NHS is a click chemistry reagent, it contains a Tetrazine group that can undergo an inverse electron demand Diels-Alder reaction (iEDDA) with molecules containing TCO groups.
