Multimodal Polysilsesquioxane Nanoparticles for Combinatorial Therapy and Gene Delivery in Triple-Negative Breast Cancer

Juneja, Ridhima; Lyles, Zachary; Vadarevu, Hemapriyadarshini; Afonin, Kirill A.; Vivero‐Escoto, Juan L.

doi:10.1021/acsami.9b00704

Cited by 37 publications

(55 citation statements)

References 69 publications

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“…Investigating different potential carriers, such as lipids or cell-penetrating peptides, for in vivo delivery of RNA therapeutics is therefore one area of RNA nanotechnology that would benefit from SAS-based approaches. Experiments with NANPs employing various carriers such as magnetic nanoparticles [81], lipids [82], mesoporous silica-based nanoparticles [79], polysilsesquioxane [83], and bolaamphiphiles or ‘bolas’ [84,85] have already been successfully initiated. The use of SANS can significantly improve our current understanding of the interactions between the NANPs and carriers, which can further improve NANP delivery in vivo.…”

Section: Discussionmentioning

confidence: 99%

Small-Angle Scattering as a Structural Probe for Nucleic Acid Nanoparticles (NANPs) in a Dynamic Solution Environment

et al. 2019

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Nucleic acid-based technologies are an emerging research focus area for pharmacological and biological studies because they are biocompatible and can be designed to produce a variety of scaffolds at the nanometer scale. The use of nucleic acids (ribonucleic acid (RNA) and/or deoxyribonucleic acid (DNA)) as building materials in programming the assemblies and their further functionalization has recently established a new exciting field of RNA and DNA nanotechnology, which have both already produced a variety of different functional nanostructures and nanodevices. It is evident that the resultant architectures require detailed structural and functional characterization and that a variety of technical approaches must be employed to promote the development of the emerging fields. Small-angle X-ray and neutron scattering (SAS) are structural characterization techniques that are well placed to determine the conformation of nucleic acid nanoparticles (NANPs) under varying solution conditions, thus allowing for the optimization of their design. SAS experiments provide information on the overall shapes and particle dimensions of macromolecules and are ideal for following conformational changes of the molecular ensemble as it behaves in solution. In addition, the inherent differences in the neutron scattering of nucleic acids, lipids, and proteins, as well as the different neutron scattering properties of the isotopes of hydrogen, combined with the ability to uniformly label biological macromolecules with deuterium, allow one to characterize the conformations and relative dispositions of the individual components within an assembly of biomolecules. This article will review the application of SAS methods and provide a summary of their successful utilization in the emerging field of NANP technology to date, as well as share our vision on its use in complementing a broad suite of structural characterization tools with some simulated results that have never been shared before.

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Section: Discussionmentioning

confidence: 99%

Small-Angle Scattering as a Structural Probe for Nucleic Acid Nanoparticles (NANPs) in a Dynamic Solution Environment

et al. 2019

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“…[7][8][9]11] PSilQ NPs have been previously used for the efficient delivery of chemotherapeutic agents, photosensitizers (PSs), nucleic acids, and contrast imaging agents. [12][13][14][15] The PSilQ nanoplatform provides similar advantages as the other silica-based nanomaterials, but with the additional benefit of having both a high content of organic functionalities in the matrix and controlled degradability. Recently, the use of PSilQ platform has been investigated to improve the performance of lightactivated treatments, such as photodynamic and photothermal therapy.…”

Section: Introductionmentioning

confidence: 99%

“…[26][27][28] We recently expanded the application of PSilQ nanoplatform for the combinatorial treatment of triple-negative breast cancer (TNBC) using chemo, photo, and gene silencing therapies. [14] Khashab and co-workers have also demonstrated the development of enzymatically degradable PSilQ NPs for in vitro imaging. [29] Nevertheless, to the best of our knowledge, all the results reported for these stimuliresponsive PSilQ NPs have been obtained only under in vitro conditions.…”

Section: Introductionmentioning

confidence: 99%

Biodegradable Silica‐Based Nanoparticles with Improved and Safe Delivery of Protoporphyrin IX for the In Vivo Photodynamic Therapy of Breast Cancer

Lyles

Tarannum

Mena

et al. 2020

Advanced Therapeutics

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Silica-based nanoplatforms are highly versatile and attractive delivery systems for cancer treatment. These platforms have been used for the effective delivery of pharmacological agents in preclinical settings. Though silicon oxide is found naturally in the human body, a major limitation associated with silica-based nanoparticles is their slow biodegradability. Therefore, the potential risks related to the longer bioaccumulation of these materials can be significant. In this work, the synthesis and application of a novel silica-based nanoplatform, polysilsesquioxane nanoparticles (PSilQ NPs) is reported. The developed PSilQ material contains stimuli-responsive properties, and improves biodegradability for the efficient delivery of a clinically relevant photosensitizer, protoporphyrin IX. Herein, it is demonstrated that the PSilQ nanoplatform is biocompatible and exhibits enhanced biodegradability in an immune-competent mouse model. In addition, PSilQ NPs show phototherapeutic efficiency for reducing the tumor burden in an orthotopic model of triple-negative breast cancer. These results may pave the way for the future clinical evaluation of this silica-based nanoplatform.

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“…Further optimization of stability, as well as targeted delivery to the cells or tissues of interest, can be achieved by complexing these materials with delivery carriers [90]. Cationic lipids, bolaamphiphiles, poly-and lipoplexes, and inorganic nanoparticles have been described in the literature, as most common carriers used for NANPs [72,73,80,[91][92][93][94], as seen in Figure 3. To study tissue distribution, NANPs are commonly labeled with fluorescent probes.…”

Section: Delivery and Distribution To And Within Tissues And Cellsmentioning

confidence: 99%

Nucleic Acid Nanoparticles at a Crossroads of Vaccines and Immunotherapies

Dobrovolskaia¹

2019

Molecules

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Vaccines and immunotherapies involve a variety of technologies and act through different mechanisms to achieve a common goal, which is to optimize the immune response against an antigen. The antigen could be a molecule expressed on a pathogen (e.g., a disease-causing bacterium, a virus or another microorganism), abnormal or damaged host cells (e.g., cancer cells), environmental agent (e.g., nicotine from a tobacco smoke), or an allergen (e.g., pollen or food protein). Immunogenic vaccines and therapies optimize the immune response to improve the eradication of the pathogen or damaged cells. In contrast, tolerogenic vaccines and therapies retrain or blunt the immune response to antigens, which are recognized by the immune system as harmful to the host. To optimize the immune response to either improve the immunogenicity or induce tolerance, researchers employ different routes of administration, antigen-delivery systems, and adjuvants. Nanocarriers and adjuvants are of particular interest to the fields of vaccines and immunotherapy as they allow for targeted delivery of the antigens and direct the immune response against these antigens in desirable direction (i.e., to either enhance immunogenicity or induce tolerance). Recently, nanoparticles gained particular attention as antigen carriers and adjuvants. This review focuses on a particular subclass of nanoparticles, which are made of nucleic acids, so-called nucleic acid nanoparticles or NANPs. Immunological properties of these novel materials and considerations for their clinical translation are discussed.

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Multimodal Polysilsesquioxane Nanoparticles for Combinatorial Therapy and Gene Delivery in Triple-Negative Breast Cancer

Cited by 37 publications

References 69 publications

Small-Angle Scattering as a Structural Probe for Nucleic Acid Nanoparticles (NANPs) in a Dynamic Solution Environment

Small-Angle Scattering as a Structural Probe for Nucleic Acid Nanoparticles (NANPs) in a Dynamic Solution Environment

Biodegradable Silica‐Based Nanoparticles with Improved and Safe Delivery of Protoporphyrin IX for the In Vivo Photodynamic Therapy of Breast Cancer

Nucleic Acid Nanoparticles at a Crossroads of Vaccines and Immunotherapies

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