Multifunctional Delivery Systems for Cancer Gene Therapy

McErlean, Emma; McCrudden, Cian M.; McCarthy, Helen

doi:10.5772/61297

Cited by 6 publications

(8 citation statements)

References 214 publications

(237 reference statements)

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“…In recent times, regulatory authorities have placed rigorous health and environmental laws in place to ensure products are carefully assessed before entry into and during clinical development [88]. In addition, difficulty in large-scale production and limitation in size of cargo have slowed the progression of viral vectors [89].…”

Section: Viral Delivery Vehiclesmentioning

confidence: 99%

Delivery across the blood-brain barrier: nanomedicine for glioblastoma multiforme

Jena

McErlean

McCarthy

2019

Drug Deliv. and Transl. Res.

118

103

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The malignant brain cancer, glioblastoma multiforme (GBM), is heterogeneous, infiltrative, and associated with chemo-and radioresistance. Despite pharmacological advances, prognosis is poor. Delivery into the brain is hampered by the blood-brain barrier (BBB), which limits the efficacy of both conventional and novel therapies at the target site. Current treatments for GBM remain palliative rather than curative; therefore, innovative delivery strategies are required and nanoparticles (NPs) are at the forefront of future solutions. Since the FDA approval of Doxil® (1995) and Abraxane (2005), the first generation of nanomedicines, development of nano-based therapies as anti-cancer treatments has escalated. A new generation of NPs has been investigated to efficiently deliver therapeutic agents to the brain, overcoming the restrictive properties of the BBB. This review discusses obstacles encountered with systemic administration along with integration of NPs incorporated with conventional and emerging treatments. Barriers to brain drug delivery, NP transport mechanisms across the BBB, effect of opsonisation on NPs administered systemically, and peptides as NP systems are addressed. Keywords BBB. Cell penetrating peptides. Drug delivery. GBM. Nanoparticle. RALA Abbreviations Au PENP P o l y e t h y l e n e i m i n e-e n t r a p p e d g o l d nanoparticles Au Gold BBB Blood-brain barrier Bcl-2 B cell lymphoma-2 BCRP Breast cancer resistance protein BMEC Brain microvascular endothelial cell c(RGD) Cyclic (arginine-glycine-aspartic acid) peptide C h o l-P C L-LNP PEGylated cleavage lipopeptide CNS Central nervous system CPP Cell penetrating peptide D M-P C L-LNP Dimyristoyl anchored PEGylated MMPcleavable lipopeptide DSPE 1 , 2-D i s t e a r o y l-s n-g l y c e r o-3phosphoethanolamine DTC Dithiolane-functionalized trimethylene carbonate EB

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Section: Viral Delivery Vehiclesmentioning

confidence: 99%

Delivery across the blood-brain barrier: nanomedicine for glioblastoma multiforme

Jena

McErlean

McCarthy

2019

Drug Deliv. and Transl. Res.

118

103

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“…Due to their ability to transfer their genetic material into host cells, viral vectors present higher transfection efficiency. 37 , 40 However, there are difficulties in large-scale production mainly due to the size of the carried DNA, mutagenesis, 41 toxicity and immunogenicity, 37 which limit the viral vectors progression. Nonviral vectors have the ability to deliver nucleic acids into cells, with lower transfection efficiency than viral vectors, 41 but are safer, 37 protect the cargo from the immune system and can manage larger DNA fragments.…”

Section: Delivery Systems Used In Cancer Researchmentioning

confidence: 99%

“… 37 , 40 However, there are difficulties in large-scale production mainly due to the size of the carried DNA, mutagenesis, 41 toxicity and immunogenicity, 37 which limit the viral vectors progression. Nonviral vectors have the ability to deliver nucleic acids into cells, with lower transfection efficiency than viral vectors, 41 but are safer, 37 protect the cargo from the immune system and can manage larger DNA fragments. 40 In cancer therapy, it is important to use efficient vectors that can surpass different natural barriers such as extracellular and intracellular membranes, and deliver the genetic material to its target site.…”

Section: Delivery Systems Used In Cancer Researchmentioning

confidence: 99%

The new era of nanotechnology, an alternative to change cancer treatment

Jurj

Braicu

Pop

et al. 2017

DDDT

155

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In the last few years, nanostructures have gained considerable interest for the safe delivery of therapeutic agents. Several therapeutic approaches have been reported, such as molecular diagnosis, disease detection, nanoscale immunotherapy and anticancer drug delivery that could be integrated into clinical use. The current paper aims to highlight the background that supports the use of nanoparticles conjugated with different types of therapeutic agents, applicable in targeted therapy and cancer research, with a special emphasis on hematological malignancies. A particular key point is the functional characterization of nonviral delivery systems, such as gold nanoparticles, liposomes and dendrimers. The paper also presents relevant published data related to microRNA and RNA interference delivery using nanoparticles in cancer therapy.

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“…[79] Similarly, cyclodextrins undergo unspecific (clathrin independent) uptake [80] but also serve to improve water-solubility and biodistribution of the cargo due to their cyclic oligosaccharide nature. [81] In the case of CPPs, uptake may occur either through transitory micelle formation, endocytosis in its four variants, or direct penetration driven by penetratin or TAT (GRKKR-RQRRR) domains, [82] which explains their documented high transfection efficiencies. [76] Overall, dendrimers, cyclodextrins, and CPPs offer extensive versatility in their structure and associated phys-chem properties, ultimately allowing the formation of the complexes to occur through charge adsorption or physical encapsulation; research in adapting and optimizing these vectors for miRNA delivery will undoubtedly impact the application of miRNA therapeutics in RM.…”

Section: Nonviral Vectorsmentioning

confidence: 99%

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Curtin

Castaño

O’Brien

2017

Adv Healthcare Materials

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The field of "regenerative medicine" (RM) was conceptually developed to aid the body's natural capacity to self-repair, a capacity which is impaired with age and in cases of disease or injury. [1] RM is a vast and multifaceted area of medicine, often microRNA-based therapies are an advantageous strategy with applications in both regenerative medicine (RM) and cancer treatments. microRNAs (miRNAs) are an evolutionary conserved class of small RNA molecules that modulate up to one third of the human nonprotein coding genome. Thus, synthetic miRNA activators and inhibitors hold immense potential to finely balance gene expression and reestablish tissue health. Ongoing industrysponsored clinical trials inspire a new miRNA therapeutics era, but progress largely relies on the development of safe and efficient delivery systems. The emerging application of biomaterial scaffolds for this purpose offers spatiotemporal control and circumvents biological and mechanical barriers that impede successful miRNA delivery. The nascent research in scaffold-mediated miRNA therapies translates know-how learnt from studies in antitumoral and genetic disorders as well as work on plasmid (p)DNA/siRNA delivery to expand the miRNA therapies arena. In this progress report, the state of the art methods of regulating miRNAs are reviewed. Relevant miRNA delivery vectors and scaffold systems applied to-date for RM and cancer treatment applications are discussed, as well as the challenges involved in their design. Overall, this progress report demonstrates the opportunity that exists for the application of miRNA-activated scaffolds in the future of RM and cancer treatments.Regenerative Medicine

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Multifunctional Delivery Systems for Cancer Gene Therapy

Cited by 6 publications

References 214 publications

Delivery across the blood-brain barrier: nanomedicine for glioblastoma multiforme

Delivery across the blood-brain barrier: nanomedicine for glioblastoma multiforme

The new era of nanotechnology, an alternative to change cancer treatment

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

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