Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors

Granot-Matok, Yasmin; Ezra, Assaf; Ramishetti, Srinivas; Sharma, Preeti; Naidu, Gonna Somu; Benhar, Itai; Peer, Dan

doi:10.7150/thno.82228

Cited by 8 publications

(2 citation statements)

References 64 publications

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“…These drawbacks led scientists to look for other mRNA carriers, which resulted in taking advantage of nanoparticles, in particular the lipid and polymeric-based nanoparticles, to develop versatile, effective, and safe carriers for mRNA delivery [364][365][366][367][368]. Some of these lipid/polymeric-based methods are based on using protamine (cationic peptide) [369][370][371], cationic lipids [372,373], and polymers, including dendrimers and chitosan [374][375][376], as well as lipid nanoparticles [352,365,377], which are conjugated with other polymers like polyethylene glycol (PEG) to increase the stability. In the case of lipid carriers, cholesterol and other natural lipids present in the membrane have been applied to enhance the efficacy.…”

Section: Mrna-based Vaccinesmentioning

confidence: 99%

Recent Findings on Therapeutic Cancer Vaccines: An Updated Review

Sheikhlary,

Lopez,

Moghimi

et al. 2024

Biomolecules

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Cancer remains one of the global leading causes of death and various vaccines have been developed over the years against it, including cell-based, nucleic acid-based, and viral-based cancer vaccines. Although many vaccines have been effective in in vivo and clinical studies and some have been FDA-approved, there are major limitations to overcome: (1) developing one universal vaccine for a specific cancer is difficult, as tumors with different antigens are different for different individuals, (2) the tumor antigens may be similar to the body’s own antigens, and (3) there is the possibility of cancer recurrence. Therefore, developing personalized cancer vaccines with the ability to distinguish between the tumor and the body’s antigens is indispensable. This paper provides a comprehensive review of different types of cancer vaccines and highlights important factors necessary for developing efficient cancer vaccines. Moreover, the application of other technologies in cancer therapy is discussed. Finally, several insights and conclusions are presented, such as the possibility of using cold plasma and cancer stem cells in developing future cancer vaccines, to tackle the major limitations in the cancer vaccine developmental process.

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Section: Mrna-based Vaccinesmentioning

confidence: 99%

Recent Findings on Therapeutic Cancer Vaccines: An Updated Review

Sheikhlary,

Lopez,

Moghimi

et al. 2024

Biomolecules

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“…Spherical bipartite structures made of a hydrogel core enclosed within a lipid bilayer ("lipobeads") may serve as nanometer sized, biocompatible, multifunctional systems for targeted anticancer drug delivery [1][2][3]. Being conceptually similar to lipid nanoparticles (LNP) [4,5], lipobeads could be promising for DNA/RNA therapeutics and for a wide range of infectious, genetic, neurodegenerative diseases and cancers. An ultimate goal in chemotherapy is superior tumor response and minimal side-effects even at high drug loading concentrations.…”

Section: Introductionmentioning

confidence: 99%

Degradation Kinetics of Disulfide Cross-Linked Microgels: Real-Time Monitoring by Confocal Microscopy

Mercer,

Italiano,

Gazaryan

et al. 2023

Gels

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Although biodegradable microgels represent a useful drug delivery system, questions remain regarding the kinetics of gel degradation and subsequent drug release. Spherical microgels (~Ø10–300 µm) were synthesized using an inverse suspension polymerization method. Specifically, acrylamide and acrylonitrile monomers were thermally co-polymerized with N,N’-bis(acryloyl)cystamine as a cross-linker with disulfide bridges. The kinetics and mechanism of degradation of these cross-linked, degradable, fluorescently labeled microgels (PAAm-AN-BAC-FA) were quantitatively studied under confocal microscopy at various concentrations of glutathione (reducing agent) ranging from 0.06 to 91.8 mM. It was found that polymer network degradation via the cleavage of disulfide bonds was accompanied by two overlapping processes: diffusion-driven swelling and dissolution-driven erosion. A slow increase in microgel size (swelling) resulted from partial de-cross-linking in the bulk of the microgel, whereas a faster decrease in fluorescence intensity (erosion) resulted from the complete cleavage of disulfide bonds and the release of uncleaved polymeric chains from the microgel immediate surface into the solution. Swelling and erosion exhibited distinct kinetics and characteristic times. Importantly, the dependence of kinetics on glutathione concentration for both swelling and erosion suggests that degradation would occur faster in cancer cells (higher concentration of reductants) than in normal cells (lower concentration of reductants), such that drug release profiles would be correspondingly different. A greater comprehension of microgel degradation kinetics would help in (i) predicting the drug release profiles for novel multifunctional drug delivery systems and (ii) using redox-sensitive degradable hydrogel particles to determine the concentrations of reducing agents either in vitro or in vivo.

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Recent Advances in Bacterium‐Based Therapeutic Modalities for Melanoma Treatment

Khan,

Dong,

Ullah

et al. 2024

Adv Healthcare Materials

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Melanoma is one of the most severe skin cancer indications with rapid progression and a high risk of metastasis. However, despite the accumulated advances in melanoma treatment including adjuvant radiation, chemotherapy, and immunotherapy, the overall melanoma treatment efficacy in the clinics is still not satisfactory. Interestingly, bacterial therapeutics have demonstrated unique properties for tumor‐related therapeutic applications, such as tumor‐targeted motility, tailorable cytotoxicity, and immunomodulatory capacity of the tumor microenvironment, which have emerged as a promising platform for melanoma therapy. Indeed, the recent advances in genetic engineering and nanotechnologies have boosted the application potential of bacterium‐based therapeutics for treating melanoma by further enhancing their tumor‐homing, cell‐killing, drug delivery, and immunostimulatory capacities. This review provides a comprehensive summary of the state‐of‐the‐art bacterium‐based anti‐melanoma modalities, which are categorized according to their unique functional merits, including tumor‐specific cytotoxins, tumor‐targeted drug delivery platforms, and immune‐stimulatory agents. Furthermore, a perspective is provided discussing the potential challenges and breakthroughs in this area. The insights in this review may facilitate the development of more advanced bacterium‐based therapeutic modalities for improved melanoma treatment efficacy.

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Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors

Cited by 8 publications

References 64 publications

Recent Findings on Therapeutic Cancer Vaccines: An Updated Review

Recent Findings on Therapeutic Cancer Vaccines: An Updated Review

Degradation Kinetics of Disulfide Cross-Linked Microgels: Real-Time Monitoring by Confocal Microscopy

Recent Advances in Bacterium‐Based Therapeutic Modalities for Melanoma Treatment

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