“…5a). In murine xenograft models of breast cancer, the conjugated form of AZA showed enhanced therapeutic efficacy compared to free AZA, including increased drug solubility and bioavailability, enrichment in cancer cells, pH-sensitive drug release, and a greater anti-proliferative effect [120]. Fig.…”
Section: Epigenetic Approaches In Nanomedicinementioning
The emergence of nanotechnology applied to medicine has revolutionized the treatment of human cancer. As in the case of classic drugs for the treatment of cancer, epigenetic drugs have evolved in terms of their specificity and efficiency, especially because of the possibility of using more effective transport and delivery systems. The use of nanoparticles (NPs) in oncology management offers promising advantages in terms of the efficacy of cancer treatments, but it is still unclear how these NPs may be affecting the epigenome such that safe routine use is ensured. In this work, we summarize the importance of the epigenetic alterations identified in human cancer, which have led to the appearance of biomarkers or epigenetic drugs in precision medicine, and we describe the transport and release systems of the epigenetic drugs that have been developed to date.
“…5a). In murine xenograft models of breast cancer, the conjugated form of AZA showed enhanced therapeutic efficacy compared to free AZA, including increased drug solubility and bioavailability, enrichment in cancer cells, pH-sensitive drug release, and a greater anti-proliferative effect [120]. Fig.…”
Section: Epigenetic Approaches In Nanomedicinementioning
The emergence of nanotechnology applied to medicine has revolutionized the treatment of human cancer. As in the case of classic drugs for the treatment of cancer, epigenetic drugs have evolved in terms of their specificity and efficiency, especially because of the possibility of using more effective transport and delivery systems. The use of nanoparticles (NPs) in oncology management offers promising advantages in terms of the efficacy of cancer treatments, but it is still unclear how these NPs may be affecting the epigenome such that safe routine use is ensured. In this work, we summarize the importance of the epigenetic alterations identified in human cancer, which have led to the appearance of biomarkers or epigenetic drugs in precision medicine, and we describe the transport and release systems of the epigenetic drugs that have been developed to date.
“…Nanoparticles are also used to vectorize hydrophobic epigenetic modulators (e.g. inhibitors of histone deacetylases or DNA methyltransferases) to improve their pharmacokinetics and therapeutic efficacy [119][120][121][122]. Macromolecular nanoassemblies and lipid-based nanoparticles have been used to vectorize almost all types of chemotherapeutics and several nanomedications have either already been approved by the FDA for cancer treatment or are currently evaluated in clinical trials [8,123] (Table 3).…”
Background
As a complement to the clinical development of new anticancer molecules, innovations in therapeutic vectorization aim at solving issues related to tumor specificity and associated toxicities. Nanomedicine is a rapidly evolving field that offers various solutions to increase clinical efficacy and safety.
Main
Here are presented the recent advances for different types of nanovectors of chemical and biological nature, to identify the best suited for translational research projects. These nanovectors include different types of chemically engineered nanoparticles that now come in many different flavors of ‘smart’ drug delivery systems. Alternatives with enhanced biocompatibility and a better adaptability to new types of therapeutic molecules are the cell-derived extracellular vesicles and micro-organism-derived oncolytic viruses, virus-like particles and bacterial minicells. In the first part of the review, we describe their main physical, chemical and biological properties and their potential for personalized modifications. The second part focuses on presenting the recent literature on the use of the different families of nanovectors to deliver anticancer molecules for chemotherapy, radiotherapy, nucleic acid-based therapy, modulation of the tumor microenvironment and immunotherapy.
Conclusion
This review will help the readers to better appreciate the complexity of available nanovectors and to identify the most fitting “type” for efficient and specific delivery of diverse anticancer therapies.
“…PEGylated liposomes trichostatin A, CG1521, and PXD101 [189] PEGylated liposomes with Fe complex VOR and LAQ824 [190] Hybrid lipid-polymer NPs DAC [191,192] Solid lipid NPs VOR [193] Solid lipid NPs decorated with hyaluronic acid VOR [194] Norbornene polyethylene oxide macromonomer CI-994 (tacedinaline) [195] POEG blocks VOR [196] PLGA NPs decorated with PGON belinostat and VOR [197,198] PLGE-PEG nano-micelles AZA [199] PEG-PLA di-block copolymer DAC [200] Gelatinases-stimuli di-block copolymers (PEG, PCL) DAC [201,202] LGE block copolymer VOR [203] Lipid-polymer (DSPE-PEG-COOH-PLGA-lecithin-PEG) core-shell NPs VOR and quisinostat [204] Nanogels DAC [205] 4.1.2. Solid Lipid Nanoparticles SLNs ( Figure 2B) consist of a hydrophobic lipid core composed of lipids (e.g., fatty acids, steroids, waxes, or triglycerides) that are in the solid state at room temperature.…”
Section: Nanocarrier Loaded Drug Referencementioning
confidence: 99%
“…The micelles are predominantly utilized as versatile nanocarriers for the delivery of DNMT inhibitors. Encapsulation of AZA or DAC into micelles has increased their stability under physiological conditions, markedly enhanced their therapeutic efficacy, provided controlled pH-dependent drug release, significantly down-regulated DNMT1 and DNMT3b expression, and increased expression of caspase-9 in murine xenograft models of BC [199,200]. Intelligent DAC-loaded micelles have been prepared by inserting cancer-specific gelatinase-cleavable peptide between two polymers.…”
Epigenetic dysregulation has been recognized as a critical factor contributing to the development of resistance against standard chemotherapy and to breast cancer progression via epithelial-to-mesenchymal transition. Although the efficacy of the first-generation epigenetic drugs (epi-drugs) in solid tumor management has been disappointing, there is an increasing body of evidence showing that epigenome modulation, in synergy with other therapeutic approaches, could play an important role in cancer treatment, reversing acquired therapy resistance. However, the epigenetic therapy of solid malignancies is not straightforward. The emergence of nanotechnologies applied to medicine has brought new opportunities to advance the targeted delivery of epi-drugs while improving their stability and solubility, and minimizing off-target effects. Furthermore, the omics technologies, as powerful molecular epidemiology screening tools, enable new diagnostic and prognostic epigenetic biomarker identification, allowing for patient stratification and tailored management. In combination with new-generation epi-drugs, nanomedicine can help to overcome low therapeutic efficacy in treatment-resistant tumors. This review provides an overview of ongoing clinical trials focusing on combination therapies employing epi-drugs for breast cancer treatment and summarizes the latest nano-based targeted delivery approaches for epi-drugs. Moreover, it highlights the current limitations and obstacles associated with applying these experimental strategies in the clinics.
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