pH and redox triggered doxorubicin release from covalently linked carbon dots conjugates

Hettiarachchi, Sajini D.; Cilingir, Emel Kirbas; Maklouf, Heidi; Seven, Elif S.; Paudyal, Suraj; Vanni, Steven; Graham, Regina M.; Leblanc, Roger M.

doi:10.1039/d0nr08381j

Cited by 28 publications

(19 citation statements)

References 47 publications

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“…24 CQDs modified with hydrazone bonds enhanced Dox release at an acidic pH ( pH 5.5). 27 In another study, a hydrophobic cysteine-based polymer was conjugated with black phosphorus carbon dots (PCQDs) for the selective delivery of drugs in tumor cells. 28 Several CQD-based DDVs for targeted drug delivery have been described previously; however, the use of polyphenolic CQDs as DDVs has not been well reported.…”

Section: Introductionmentioning

confidence: 99%

Two-photon excitable membrane targeting polyphenolic carbon dots for long-term imaging and pH-responsive chemotherapeutic drug delivery for synergistic tumor therapy

et al. 2022

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Section: Introductionmentioning

confidence: 99%

Two-photon excitable membrane targeting polyphenolic carbon dots for long-term imaging and pH-responsive chemotherapeutic drug delivery for synergistic tumor therapy

et al. 2022

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“…Anabatic drug release was observed with a single trigger; for example, DTX release reached 43.7% in the presence of 50 mM DTT at pH 7.4 and 42.0% without DTT at pH 5 after 6 h. When CLip-PC@CO-LC NPs were incubated with a release medium at pH = 5 containing DTT, DTX release reached 79.0% with a fast release after 6 h. These results may be attributed to reduction-triggered disulfide bond destruction and the charge-reversal core leading to the disruption of the CLip, indicating that the biomimetic nano-delivery system remains stable in the blood circulation system and has less drug leakage. Nevertheless, the burst release of the drug can be triggered by high GSH and low pH in the TME when the NPs reach the tumor site [ 50 , 51 ].…”

Section: Resultsmentioning

confidence: 99%

Tumor microenvironment-activated cancer cell membrane-liposome hybrid nanoparticle-mediated synergistic metabolic therapy and chemotherapy for non-small cell lung cancer

et al. 2021

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Background Biomimetic nanotechnology-based RNA interference (RNAi) has been successful in improving theranostic efficacy in malignant tumors. Its integration with hybrid biomimetic membranes made of natural cell membranes fused with liposomal membranes is mutually beneficial and extends their biofunctions. However, limited research has focused on engineering such biomimetics to endow them with unique properties and functions, in particular, those essential for a “smart” drug delivery system, such as a tumor microenvironment (TME)-activated multifunctional biomimetic nanoplatform. Results Herein, we utilized an integrated hybrid nanovesicle composed of cancer cell membranes (Cm) and matrix metallopeptidase 9 (MMP-9)-switchable peptide-based charge-reversal liposome membranes (Lipm) to coat lipoic acid-modified polypeptides (LC) co-loaded with phosphoglycerate mutase 1 (PGAM1) siRNA (siPGAM1) and DTX. The nanovesicle presented a negatively charged coating (citraconic anhydride-grafted poly-l-lysine, PC) in the middle layer for pH-triggered charge conversion functionalization. The established chemotherapeutic drug (DTX) co-delivery system CLip-PC@CO-LC nanoparticles (NPs) have a particle size of ~ 193 nm and present the same surface proteins as the Cm. Confocal microscopy and flow cytometry results indicated a greater uptake of MMP-9-treated CLip-PC@CO-LC NPs compared with that of the CLip-PC@CO-LC NPs without MMP-9 pretreatment. The exposure to MMP-9 activated positively charged cell-penetrating peptides on the surface of the hybrid nanovesicles. Moreover, pH triggered membrane disruption, and redox triggered DTX and siRNA release, leading to highly potent target-gene silencing in glycolysis and chemotherapy with enhanced antiproliferation ability. The biodistribution results demonstrated that the CLip-PC@LC-DiR NPs accumulated in the tumor owing to a combination of long blood retention time, homologous targeting ability, and TME-activated characteristics. The CLip-PC@CO-LC NPs led to more effective tumor growth inhibition than the DTX and free siPGAM1 formulations. Conclusions TME-activated cancer cell membrane-liposome integrated hybrid NPs provide an encouraging nanoplatform that combines RNAi with chemotherapy for precise treatment of non-small cell lung cancer. Graphical abstract

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“…[10,11] Well-documented biocompatibility, tunable photoluminescence, excellent water solubility, ease of production, and resistance to photobleaching are among the unique characteristics of CDs. [12] Previously, we reported a carbon dots-based triple-drug delivery model that consists of two chemotherapeutic drugs and targeted ligand transferrin protein. [13] We showed that the synergistic therapeutic e cacy of the triple nano-model compared to the single drug delivery models.…”

Section: Introductionmentioning

confidence: 99%

Cell-nucleus Targeted Peptide Tethered Quadruple Carbon Dots for Treatment of High-grade Gliomas

Cilingir

Hettiarachchi

Zhou

et al. 2022

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Ultimate goal of the nanomedicine is built on the idea of robust targeted delivery of complex assemblies that contain sufficient amount of multiple therapeutics and diagnostic agents for highly localized payload release with no adverse side effects. Besides the numerous efforts on the field of cancer specific nanomedicine, still there is a great need for improvements in terms of target specificity. Previously, we have reported a target-specific carbon dots- based dual nano-drug delivery system. In study, for the first time in literature, surface functional group of the carbon dots were conjugated with four different ligands namely, two peptides (shPep-1 and lnPep-1) and two chemotherapeutic drugs (epirubicin and temozolomide). Here, we advanced our drug delivery system as a dual drug nano-carrier (quadruple nano-model) that explicitly targets the IL-13Rα2 receptors and the nucleus of high-grade glioma brain tumors. The successful conjugation of each molecule onto carbon dots (CDs) was meticulously characterized with numerous analytical techniques. Additionally, the in vitro cell viability assay revealed that quadrupole nano-model significantly reduced the cancer cell viability compared to the single peptide dual drug linked conjugates. Further, in vitro bioimaging studies using FITC conjugated single and dual peptides models, showed that dual peptide model exhibited greater FITC fluorescence throughout the cell including the nucleus compared to the single peptide models. This observation is evidence for improved cancer cell uptake and nucleus colocalization of quadrupole nano-model. Our quadrupole nano-model fully serves the ultimate goal of nanomedicine as a nanocarrier which contains two targeting peptides and two therapeutics simultaneously.

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pH and redox triggered doxorubicin release from covalently linked carbon dots conjugates

Abstract: Tumor microenvironment responsive drug delivery systems are potential approaches to reduce the acute toxicity caused by high-dose cancer chemotherapy.

Cited by 28 publications

References 47 publications

Two-photon excitable membrane targeting polyphenolic carbon dots for long-term imaging and pH-responsive chemotherapeutic drug delivery for synergistic tumor therapy

Two-photon excitable membrane targeting polyphenolic carbon dots for long-term imaging and pH-responsive chemotherapeutic drug delivery for synergistic tumor therapy

Tumor microenvironment-activated cancer cell membrane-liposome hybrid nanoparticle-mediated synergistic metabolic therapy and chemotherapy for non-small cell lung cancer

Cell-nucleus Targeted Peptide Tethered Quadruple Carbon Dots for Treatment of High-grade Gliomas

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