Diselenide–Pemetrexed Assemblies for Combined Cancer Immuno‐, Radio‐, and Chemotherapies

Li, Tianyu; Pan, Sining; Gao, Shiqian; Xiang, Wentian; Sun, Chenxing; Cao, Wei; Xu, Huaping

doi:10.1002/ange.201914453

Cited by 16 publications

(9 citation statements)

References 50 publications

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“…Se-Se bonds can also be cleaved by very mild redox signals such as H 2 O 2 and reduced GSH to form seleninic acid and selenol derivatives, respectively [62]. The observed redox stimuli-responsive propensity was primarily associated with the weak bond energy of the Se-Se bond at 172 kJ/mol [25,34,63]. This endowed diselenide containing polymers to be used in the fabrication of redox stimuli-responsive CCMs for the delivery and controlled release of CAs in tumor tissue.…”

Section: Drug-loading and Releasing Behavior Of Micellesmentioning

confidence: 99%

Fabrication of Core Crosslinked Polymeric Micelles as Nanocarriers for Doxorubicin Delivery: Self-Assembly, In Situ Diselenide Metathesis and Redox-Responsive Drug Release

et al. 2020

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Polymeric micelles (PMs) have been used to improve the poor aqueous solubility, slow absorption and non-selective biodistribution of chemotherapeutic agents (CAs), albeit, they suffer from disassembly and premature release of payloads in the bloodstream. To alleviate the thermodynamic instability of PMs, different core crosslinking approaches were employed. Herein, we synthesized the poly(ethylene oxide)-b-poly((2-aminoethyl)diselanyl)ethyl l-aspartamide)-b-polycaprolactone (mPEG-P(LA-DSeDEA)-PCL) copolymer which self-assembled into monodispersed nanoscale, 156.57 ± 4.42 nm, core crosslinked micelles (CCMs) through visible light-induced diselenide metathesis reaction between the pendant selenocystamine moieties. The CCMs demonstrated desirable doxorubicin (DOX)-loading content (7.31%) and encapsulation efficiency (42.73%). Both blank and DOX-loaded CCMs (DOX@CCMs) established appreciable colloidal stability in the presence of bovine serum albumin (BSA). The DOX@CCMs showed redox-responsive drug releasing behavior when treated with 5 and 10 mM reduced glutathione (GSH) and 0.1% H2O2. Unlike the DOX-loaded non-crosslinked micelles (DOX@NCMs) which exhibited initial burst release, DOX@CCMs demonstrated a sustained release profile in vitro where 71.7% of the encapsulated DOX was released within 72 h. In addition, the in vitro fluorescent microscope images and flow cytometry analysis confirmed the efficient cellular internalization of DOX@CCMs. The in vitro cytotoxicity test on HaCaT, MDCK, and HeLa cell lines reiterated the cytocompatibility (≥82% cell viability) of the mPEG-P(LA-DSeDEA)-PCL copolymer and DOX@CCMs selectively inhibit the viabilities of 48.85% of HeLa cells as compared to 15.75% of HaCaT and 7.85% of MDCK cells at a maximum dose of 10 µg/mL. Overall, all these appealing attributes make CCMs desirable as nanocarriers for the delivery and controlled release of DOX in tumor cells.

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Section: Drug-loading and Releasing Behavior Of Micellesmentioning

confidence: 99%

Fabrication of Core Crosslinked Polymeric Micelles as Nanocarriers for Doxorubicin Delivery: Self-Assembly, In Situ Diselenide Metathesis and Redox-Responsive Drug Release

et al. 2020

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“…Besides, the development of therapeutic resistance to chemical agents remarkably impeded the treatment and prognosis of NSCLC, comparing with the small lung cancer [5]. Alimta (also known as pemetrexed) is a multitargeted antifolate agent that has been proved to exhibit e ective single-agent activity in patients with NSCLC [6][7][8][9] and is widely studied as the synergetic agent for NSCLC therapy in various clinical studies [10][11][12][13]. However, the resistance to pemetrexed is frequently occurred in multiple cancers and severely a ects the NSCLC therapy [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

The Potential Mechanism of HDAC1-Catalyzed Histone Crotonylation of Caspase-1 in Nonsmall Cell Lung Cancer

Jiang

Liao

Yang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Nonsmall cell lung cancer (NSCLC) is a predominant subtype of lung cancer and accounts for over 80% of all lung cancer cases. The resistance to pemetrexed (PEM) is frequently occurred and severely affects the NSCLC therapy. Proteomic analysis of histones indicated that the histone deacetylase 1 (HDAC1) complex could hydrolyze lysine crotonylation on histone3 (H3K18cr), affecting epigenetic regulation in cancers. However, the effect of HDAC1-mediated H3K18cr on the PEM resistance of NSCLC is still unclear. Here, we aimed to explore the function of HDAC1-mediated H3K18cr in NSCLC PEM resistance. The expression of HDAC1 was upregulated in clinical NSCLC tissues and cell lines and correlated with the poor prognosis of NSCLC samples. We constructed the PEM-resistant NSCLC cell lines, and the depletion of HDAC1 remarkably reduced the viability of the cells. The proliferation of PEM-resistant NSCLC cells was decreased by HDAC1 knockdown, and the IC50 of PEM was repressed by the silencing of HDAC1 in the cells. Mechanically, we identified the enrichment of HDAC1 on the promoter of caspase-1 in PEM-resistant NSCLC cells. The depletion of HDAC1 inhibited the enrichment of histone H3K18cr and RNA polymerase II (RNA pol II) on the caspase-1 promoter in the cells. The expression of caspase-1 was suppressed by HDAC1 knockdown. The knockdown of HDAC1 reduced proliferation of PEM-resistant NSCLC cells, in which caspase-1 or GSDMD depletion reversed the effect. Clinically, the HDAC1 expression was negatively associated with caspase-1 and GSDMD in clinical NSCLC tissues, while caspase-1 and GSDMD expression was positively correlated in the samples. Therefore, we concluded that HDAC1-catalyzed histone crotonylation of caspase-1 modulates PEM sensitivity of NSCLC by targeting GSDMD.

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“…[ 278–280 ] Li et al developed a diselenide bridged cytosine homodimer (Cyt‐SeSe‐Cyt) to co‐assemble with pemetrexed through intermolecular hydrogen bonding (Figure 17C). [ 137 ] The prepared co‐assemblies (Pem/Se) combined immunotherapy with radiotherapy and chemotherapy. Under γ‐radiation, diselenide bonds were cleaved into seleninic acid, which could inhibit the expression of HLA‐E protein and then inducing natural killer (NK) cell‐based cancer immunity.…”

Section: Prodrug Nanoassemblies As Versatile Nanoplatform For Combination Therapymentioning

confidence: 99%

Small‐Molecule Prodrug Nanoassemblies: An Emerging Nanoplatform for Anticancer Drug Delivery

Sun

et al. 2021

Small

115

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The antitumor efficiency and clinical translation of traditional nanomedicines is mainly restricted by low drug loading, complex preparation technology, and potential toxicity caused by the overused carrier materials. In recent decades, small‐molecule prodrug nanoassemblies (SMP‐NAs), which are formed by the self‐assembly of prodrugs themselves, have been widely investigated with distinct advantages of ultrahigh drug‐loading and negligible excipients‐trigged adverse reaction. Benefited from the simple preparation process, SMP‐NAs are widely used for chemotherapy, phototherapy, immunotherapy, and tumor diagnosis. In addition, combination therapy based on the accurate co‐delivery behavior of SMP‐NAs can effectively address the challenges of tumor heterogeneity and multidrug resistance. Recent trends in SMP‐NAs are outlined, and the corresponding self‐assembly mechanisms are discussed in detail. Besides, the smart stimuli‐responsive SMP‐NAs and the combination therapy based on SMP‐NAs are summarized, with special emphasis on the structure–function relationships. Finally, the outlooks and potential challenges of SMP‐NAs in cancer therapy are highlighted.

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Diselenide–Pemetrexed Assemblies for Combined Cancer Immuno‐, Radio‐, and Chemotherapies

Cited by 16 publications

References 50 publications

Fabrication of Core Crosslinked Polymeric Micelles as Nanocarriers for Doxorubicin Delivery: Self-Assembly, In Situ Diselenide Metathesis and Redox-Responsive Drug Release

Fabrication of Core Crosslinked Polymeric Micelles as Nanocarriers for Doxorubicin Delivery: Self-Assembly, In Situ Diselenide Metathesis and Redox-Responsive Drug Release

The Potential Mechanism of HDAC1-Catalyzed Histone Crotonylation of Caspase-1 in Nonsmall Cell Lung Cancer

Small‐Molecule Prodrug Nanoassemblies: An Emerging Nanoplatform for Anticancer Drug Delivery

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