Galactose-decorated liver tumor-specific nanoliposomes incorporating selective BRD4-targeted PROTAC for hepatocellular carcinoma therapy

Saraswat, Aishwarya; Vemana, Hari Priya; Dukhande, Vikas V.; Patel, Ketan

doi:10.1016/j.heliyon.2021.e08702

Cited by 42 publications

(14 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Experimental results have also shown excellent synergistic effects of dual ARV-825 and nintedanib-loaded PEGylated nanoliposomes in melanoma, providing a new approach for the treatment of vemurafenib-resistant melanoma [ 47 ]. Experiments with ARV-825-loaded nanoliposomes in lung cancer and hepatocellular carcinoma have shown that nano-fusion leads to better tumor penetration and lethality [ 48 , 49 ].…”

Section: Protacs For Epigenetic Targets In Cancermentioning

confidence: 99%

PROTACs in Epigenetic Cancer Therapy: Current Status and Future Opportunities

et al. 2023

View full text Add to dashboard Cite

The epigenetic regulation of gene functions has been proven to be strongly associated with the development and progression of cancer. Reprogramming the cancer epigenome landscape is one of the most promising target therapies in both treatments and in reversing drug resistance. Proteolytic targeted chimeras (PROTACs) are an emerging therapeutic modality for selective degradation via the native ubiquitin-proteasome system. Rapid advances in PROTACs have facilitated the exploration of targeting epigenetic proteins, yielding effective strategies to target transcription while reducing toxicities to untransformed cells. A lot of PROTAC degraders have already been designed in the field of epigenetic cancer therapy, and PROTACs targeting epigenetic proteins can better exploit target druggability and improve the mechanistic understanding of the epigenetic regulation of cancer. Thus, this review focuses on the progress made in the development of PROTAC degraders and PROTAC drugs targeting epigenetics in cancer and discusses challenges and future opportunities for the field.

show abstract

Section: Protacs For Epigenetic Targets In Cancermentioning

confidence: 99%

PROTACs in Epigenetic Cancer Therapy: Current Status and Future Opportunities

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Lipid nanoparticles are another PROTAC carrier where additional moieties can be introduced for active cancer targeting. A. Saraswat et al explored galactose-decorated liposomes for PROTAC delivery to treat hepatocellular carcinoma [ 120 ]. The galactose on liposome surfaces was intended to specifically bind asialoglycoprotein receptors (ASGPRs) on cancer cells, and BRD4-degrading ARV-825 was loaded in the bilayer of liposomes to produce GALARV.…”

Section: Cancer-specific Protac Delivery Systemmentioning

confidence: 99%

Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy

et al. 2023

View full text Add to dashboard Cite

Proteolysis-targeting chimeras (PROTACs) are rapidly emerging as a potential therapeutic strategy for cancer therapy by inducing the degradation of tumor-overexpressing oncogenic proteins. They can specifically catalyze the degradation of target oncogenic proteins by recruiting E3 ligases and utilizing the ubiquitin-proteasome pathway. Since their mode of action is universal, irreversible, recyclable, long-lasting, and applicable to ‘undruggable’ proteins, PROTACs are gradually replacing the role of conventional small molecular inhibitors. Moreover, their application areas are being expanded to cancer immunotherapy as various types of oncogenic proteins that are involved in immunosuppressive tumor microenvironments. However, poor water solubility and low cell permeability considerably restrict the pharmacokinetic (PK) property, which necessitates the use of appropriate delivery systems for cancer immunotherapy. In this review, the general characteristics, developmental status, and PK of PROTACs are first briefly covered. Next, recent studies on the application of various types of passive or active targeting delivery systems for PROTACs are introduced, and their effects on the PK and tumor-targeting ability of PROTACs are described. Finally, recent drug delivery systems of PROTACs for cancer immunotherapy are summarized. The adoption of an adequate delivery system for PROTAC is expected to accelerate the clinical translation of PROTACs, as well as improve its efficacy for cancer therapy.

show abstract

“…Triplicates of each experiment were performed. 10 Visual Assessment of SNEDDS and Stability. The dispersibility of SNEDDS formulation batches was investigated, and the batches were evaluated for appearance on emulsification in aqueous media.…”

Section: Data Set Selectionmentioning

confidence: 99%

Investigating Key Molecular Descriptors Affecting Particle Size: A Predictive Exemplary Approach for Self-Emulsifying System

et al. 2023

Self Cite

View full text Add to dashboard Cite

The self-nano/microemulsifying drug delivery system is one of the well-established techniques for enhancing the solubility of poorly water-soluble drug molecules. The ratio of oil:surfactant:cosolvent plays a key role in globule size on dispersion into water, but there is very limited information on how a drug molecule affects the size. The rationale of this project was to illustrate the correlation between the particle size of nanoemulsion droplets and molecular descriptors of a drug. In the study, a self-nanoemulsifying preconcentrate containing drug with medium chain triglycerides (oil), dimethylacetamide (DMA, cosolvent), and Kolliphor EL (surfactant) was prepared for 40 drug molecules with diverse physicochemical properties. The selfnanoemulsifying preconcentrate was dispersed in water, and dynamic light scattering particle size was analyzed. A majority of drugs showed a significant increase in globule size compared to blank formulation, while few drugs showed a stark reduction in globule size. It is interesting to understand the attributes of molecules driving the self-emulsification and the diameter of nanoglobules. A systematic correlation of resultant particle size with 1D, 2D, and 3D molecular descriptors (overall more than 700 descriptors) was carried out for the data set using the PaDEL tool kit. The data compilation, curation, and analysis were performed using the SIMCA14 software. In the process of molecular descriptors screening, thereafter curation, 50 descriptors were selected using the genetic algorithm screening. The PLS-DA statistical method was employed for conversion of data into binomial systems. Final group of 5 descriptors: SpMiSpMin2_Bhe, RNCS, TDB9i, JG17, and ETA_Shape showed the correlation with particle size and classifying the drug molecules facilitating increase or decrease in particle size.

show abstract

Galactose-decorated liver tumor-specific nanoliposomes incorporating selective BRD4-targeted PROTAC for hepatocellular carcinoma therapy

Cited by 42 publications

References 53 publications

PROTACs in Epigenetic Cancer Therapy: Current Status and Future Opportunities

PROTACs in Epigenetic Cancer Therapy: Current Status and Future Opportunities

Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy

Investigating Key Molecular Descriptors Affecting Particle Size: A Predictive Exemplary Approach for Self-Emulsifying System

Contact Info

Product

Resources

About