Oral lipid nanocomplex of BRD4 PROteolysis TArgeting Chimera and vemurafenib for drug-resistant malignant melanoma

Saraswat, Aishwarya; Vartak, Richa; Hegazy, Rehab; Fu, Yige; Rao, Trishaal Janardhanam Raghavendra; Billack, Blase; Patel, Ketan

doi:10.1016/j.biopha.2023.115754

Cited by 11 publications

(2 citation statements)

References 29 publications

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“…For instance, Safaei et al [ 40 ] developed a transmembrane peptide (TAT)-conjugated liposomal nanocarrier for the delivery of trastuzumab and siRNA targeting breast cancer resistance protein (BCRP) to overcome multidrug resistance in breast cancer. Similarly, Saraswat and colleagues developed an oral lipid nanoparticle-based delivery system encapsulating ARV-825 and vemurafenib (VEM) for the treatment of BRAFi-resistant melanoma [ 41 ]. They conducted functional studies of VEM resistance in both 2D and 3D tumor spheroids in vitro and investigated the pharmacokinetics and anticancer efficacy in vivo, effectively demonstrating the application value and potential of lipid-based composite drugs in the treatment of resistant tumors.…”

Section: Discussionmentioning

confidence: 99%

Folate-modified liposomes mediate the co-delivery of cisplatin with miR-219a-5p for the targeted treatment of cisplatin-resistant lung cancer

Wu,

Zhang,

Zhao

et al. 2024

BMC Pulm Med

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Cisplatin (DDP) resistance, often leading to first-line chemotherapy failure in non-small cell lung cancer (NSCLC), poses a significant challenge. MiR-219a-5p has been reported to enhance the sensitivity of human NSCLC to DDP. However, free miR-219a-5p is prone to degradation by nucleases in the bloodstream, rendering it unstable. In light of this, our study developed an efficient nanodrug delivery system that achieved targeted delivery of DDP and miR-219a-5p by modifying liposomes with folate (FA). Based on the results of material characterization, we successfully constructed a well-dispersed and uniformly sized (approximately 135.8 nm) Lipo@DDP@miR-219a-5p@FA nanodrug. Agarose gel electrophoresis experiments demonstrated that Lipo@DDP@miR-219a-5p@FA exhibited good stability in serum, effectively protecting miR-219a-5p from degradation. Immunofluorescence and flow cytometry experiments revealed that, due to FA modification, Lipo@DDP@miR-219a-5p@FA could specifically bind to FA receptors on the surface of tumor cells (A549), thus enhancing drug internalization efficiency. Safety evaluations conducted in vitro demonstrated that Lipo@DDP@miR-219a-5p@FA exhibited no significant toxicity to non-cancer cells (BEAS-2B) and displayed excellent blood compatibility. Cellular functional experiments, apoptosis assays, and western blot demonstrated that Lipo@DDP@miR-219a-5p@FA effectively reversed DDP resistance in A549 cells, inhibited cell proliferation and migration, and further promoted apoptosis. In summary, the Lipo@DDP@miR-219a-5p@FA nanodrug, through specific targeting of cancer cells and reducing their resistance to DDP, significantly enhanced the anti-NSCLC effects of DDP in vitro, providing a promising therapeutic option for the clinical treatment of NSCLC.

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Section: Discussionmentioning

confidence: 99%

Folate-modified liposomes mediate the co-delivery of cisplatin with miR-219a-5p for the targeted treatment of cisplatin-resistant lung cancer

Wu,

Zhang,

Zhao

et al. 2024

BMC Pulm Med

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“…After a specific incubation period, cell viability was evaluated via CCK-8 assays (Bioexplorer, B4007-016). Moreover, invasion study of 3D multicellular tumor spheroids was described previously [ 40 – 42 ], briefly, stable overexpression or knockdown of miR-151-5p on HN12 cell and HN30 cell were seed cells into 96-well round bottom Ultra-Low Attachment plate (Corning, No. 7007) at 5000 cells per well.…”

Section: Methodsmentioning

confidence: 99%

m6A-dependent mature miR-151-5p accelerates the malignant process of HNSCC by targeting LYPD3

Huang,

Ren,

Hua

et al. 2024

Mol Biomed

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AbstractmiRNA has emerged as a crucial regulator in various of pathological and physiological processes, yet its precise mechanism of action the detailed mechanism of their action in Head and neck squamous cell carcinoma (HNSCC) remains incompletely understood. This study sheds light on the role of mi-151-5p, revealing its significantly elevated expression in tumor cells, which notably enhances the invasion and migration of HNSCC cells. This effect is achieved through directly targeting LY6/PLAUR Domain Containing 3 (LYPD3) by miR-151-5p, involving complementary binding to the 3’-untranslated regions (3’-UTR) in the mRNA of LYPD3. Consequently, this interaction accelerates the metastasis of HNSCC. Notably, clinical observations indicate a correlation between high expression of miR-151-5p and low levels of LYPD3 in clinical settings are correlated with poor prognosis of HNSCC patients. Furthermore, our investigation demonstrates that glycosylation of LYPD3 modulates its subcellular localization and reinforces its role in suppressing HNSCC metastasis. Additionally, we uncover a potential regulatory mechanism involving the facilitation of miR-151-5p maturation and accumulation through N6-methyladenosine (m6A) modification. This process is orchestrated by methyltransferase-like 3 (METTL3) and mediated by a newly identified reader, heterogeneous nuclear ribonucleoprotein U (hnRNP U). These findings collectively underscore the significance of the METTL3/miR-151-5p/LYPD3 axis serves as a prominent driver in the malignant progression of HNSCC.

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Recent breakthroughs in innovative elements, multidimensional enhancements, derived technologies, and novel applications of PROTACs

Zhang,

Zeng,

et al. 2024

Biomedicine & Pharmacotherapy

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Oral lipid nanocomplex of BRD4 PROteolysis TArgeting Chimera and vemurafenib for drug-resistant malignant melanoma

Cited by 11 publications

References 29 publications

Folate-modified liposomes mediate the co-delivery of cisplatin with miR-219a-5p for the targeted treatment of cisplatin-resistant lung cancer

Folate-modified liposomes mediate the co-delivery of cisplatin with miR-219a-5p for the targeted treatment of cisplatin-resistant lung cancer

m6A-dependent mature miR-151-5p accelerates the malignant process of HNSCC by targeting LYPD3

Recent breakthroughs in innovative elements, multidimensional enhancements, derived technologies, and novel applications of PROTACs

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