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Article ; Online: Drug delivery for metabolism targeted cancer immunotherapy.

Khodaei, Taravat / Inamdar, Sahil / Suresh, Abhirami P / Acharya, Abhinav P

2022 Volume 184, Page(s) 114242

Abstract: Drug delivery vehicles have made a great impact on cancer immunotherapies in clinics and pre-clinical research. Notably, the science of delivery of cancer vaccines and immunotherapeutics, modulating immune cell functions has inspired development of ... ...

Abstract	Drug delivery vehicles have made a great impact on cancer immunotherapies in clinics and pre-clinical research. Notably, the science of delivery of cancer vaccines and immunotherapeutics, modulating immune cell functions has inspired development of several successful companies and clinical products. Interestingly, these drug delivery modalities not only modulate the function of immune cells (often quantified at the mRNA and protein levels), but also modulate the metabolism of these cells. Specifically, cancer immunotherapy often leads to activation of different immune cells such as dendritic cells, macrophages and T cells, which is driven by energy metabolism of these cells. Recently, there has been a great excitement about interventions that can directly modulate the energy metabolism of these immune cells and thus affect their function and in turn lead to a robust cancer immune response. Here we review few strategies that have been tested in clinic and pre-clinical research for generating effective metabolism-associated cancer therapies and immunotherapies.
MeSH term(s)	Cancer Vaccines/therapeutic use ; Drug Delivery Systems ; Humans ; Immunotherapy ; Neoplasms/drug therapy ; T-Lymphocytes
Chemical Substances	Cancer Vaccines
Language	English
Publishing date	2022-03-31
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
DOI	10.1016/j.addr.2022.114242
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Article ; Online: Covalent Organic Frameworks for Biomedical Applications.

Esrafili, Arezoo / Wagner, Avery / Inamdar, Sahil / Acharya, Abhinav P

Advanced healthcare materials

2021 Volume 10, Issue 6, Page(s) e2002090

Abstract: Covalent organic frameworks (COFs) are porous organic polymeric materials that are composed of organic elements and linked together by the thermodynamically stable covalent bonds. The applications of COFs in energy sector and drug delivery are afforded ... ...

Abstract	Covalent organic frameworks (COFs) are porous organic polymeric materials that are composed of organic elements and linked together by the thermodynamically stable covalent bonds. The applications of COFs in energy sector and drug delivery are afforded because of the desirable properties of COFs, such as high stability, low density, large surface area, multidimensionality, porosity, and high-ordered crystalline structure expanded. In this review COFs are reviewed, from the perspective of different types of reported COFs, different methods for their synthesis, and their potential applications in the biomedical field. The main goal of this review is to introduce COFs as a biomaterial and to identify specific advantages of different types of COFs that can be exploited for specialized biomedical applications, such as immune engineering.
MeSH term(s)	Metal-Organic Frameworks ; Polymers ; Porosity
Chemical Substances	Metal-Organic Frameworks ; Polymers
Language	English
Publishing date	2021-01-21
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2649576-4
ISSN	2192-2659 ; 2192-2640
ISSN (online)	2192-2659
ISSN	2192-2640
DOI	10.1002/adhm.202002090
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Zs.A 6966: Show issues

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Article ; Online: Short term, low dose alpha-ketoglutarate based polymeric nanoparticles with methotrexate reverse rheumatoid arthritis symptoms in mice and modulate T helper cell responses.

Mangal, Joslyn L / Inamdar, Sahil / Suresh, Abhirami P / Jaggarapu, Madhan Mohan Chandra Sekhar / Esrafili, Arezoo / Ng, Nathan D / Acharya, Abhinav P

Biomaterials science

2022 Volume 10, Issue 23, Page(s) 6688–6697

Abstract: Activated effector T cells induce pro-inflammatory responses in rheumatoid arthritis (RA) which then lead to inflammation of the joints. In this report, we demonstrate that polymeric nanoparticles with alpha keto-glutarate (aKG) in their polymer backbone ...

Abstract	Activated effector T cells induce pro-inflammatory responses in rheumatoid arthritis (RA) which then lead to inflammation of the joints. In this report, we demonstrate that polymeric nanoparticles with alpha keto-glutarate (aKG) in their polymer backbone (termed as paKG NPs) modulate T cell responses
MeSH term(s)	Mice ; Animals ; Methotrexate/pharmacology ; Methotrexate/therapeutic use ; Ketoglutaric Acids/therapeutic use ; Mice, Inbred DBA ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Experimental/chemically induced ; Arthritis, Experimental/drug therapy ; T-Lymphocytes, Helper-Inducer/metabolism ; Nanoparticles ; Polymers/therapeutic use
Chemical Substances	Methotrexate (YL5FZ2Y5U1) ; Ketoglutaric Acids ; Polymers
Language	English
Publishing date	2022-11-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d2bm00415a
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Alpha-ketoglutaric acid based polymeric particles for cutaneous wound healing.

Jaggarapu, Madhan M C S / Ghosh, Deepanjan / Johnston, Tyler / Yaron, Jordan R / Mangal, Joslyn L / Inamdar, Sahil / Gosangi, Mallikarjun / Rege, Kaushal / Acharya, Abhinav P

Journal of biomedical materials research. Part A

2023 Volume 111, Issue 9, Page(s) 1372–1378

Abstract: Metabolites are not only involved in energy pathways but can also act as signaling molecules. Herein, we demonstrate that polyesters of alpha-ketoglutararte (paKG) can be generated by reacting aKG with aliphatic diols of different lengths, which release ... ...

Abstract	Metabolites are not only involved in energy pathways but can also act as signaling molecules. Herein, we demonstrate that polyesters of alpha-ketoglutararte (paKG) can be generated by reacting aKG with aliphatic diols of different lengths, which release aKG in a sustained manner. paKG polymer-based microparticles generated via emulsion-evaporation technique lead to faster keratinocyte wound closures in a scratch assay test. Moreover, paKG microparticles also led to faster wound healing responses in an excisional wound model in live mice. Overall, this study shows that paKG MPs that release aKG in a sustained manner can be used to develop regenerative therapeutic responses.
MeSH term(s)	Animals ; Mice ; Ketoglutaric Acids/pharmacology ; Ketoglutaric Acids/metabolism ; Polymers ; Polyesters ; Wound Healing
Chemical Substances	Ketoglutaric Acids ; Polymers ; Polyesters
Language	English
Publishing date	2023-03-23
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2099989-6
ISSN	1552-4965 ; 1549-3296 ; 0021-9304
ISSN (online)	1552-4965
ISSN	1549-3296 ; 0021-9304
DOI	10.1002/jbm.a.37539
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Article ; Online: Succinate in the tumor microenvironment affects tumor growth and modulates tumor associated macrophages.

Inamdar, Sahil / Suresh, Abhirami P / Mangal, Joslyn L / Ng, Nathan D / Sundem, Alison / Behbahani, Hoda Shokrollahzadeh / Rubino, Thomas E / Yaron, Jordan R / Khodaei, Taravat / Green, Matthew / Curtis, Marion / Acharya, Abhinav P

Biomaterials

2023 Volume 301, Page(s) 122292

Abstract: Succinate is an important metabolite that modulates metabolism of immune cells and cancer cells in the tumor microenvironment (TME). Herein, we report that polyethylene succinate (PES) microparticles (MPs) biomaterial mediated controlled delivery of ... ...

Abstract	Succinate is an important metabolite that modulates metabolism of immune cells and cancer cells in the tumor microenvironment (TME). Herein, we report that polyethylene succinate (PES) microparticles (MPs) biomaterial mediated controlled delivery of succinate in the TME modulates macrophage responses. Administering PES MPs locally with or without a BRAF inhibitor systemically in an immune-defective aging mice with clinically relevant BRAF
MeSH term(s)	Animals ; Mice ; Succinic Acid ; Tumor-Associated Macrophages ; Tumor Microenvironment ; Proto-Oncogene Proteins B-raf ; Succinates ; Melanoma
Chemical Substances	Succinic Acid (AB6MNQ6J6L) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; poly(ethylene succinate) ; Succinates
Language	English
Publishing date	2023-08-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2023.122292
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Article ; Online: Versatile Detection and Monitoring of Ionizing Radiation Treatment Using Radiation-Responsive Gel Nanosensors.

Pushpavanam, Karthik / Dutta, Subhadeep / Inamdar, Sahil / Bista, Tomasz / Sokolowski, Thaddeus / Rapchak, Alek / Sadeghi, Amir / Sapareto, Stephen / Rege, Kaushal

ACS applied materials & interfaces

2022 Volume 14, Issue 13, Page(s) 14997–15007

Abstract: Modern radiation therapy workflow involves complex processes intended to maximize the radiation dose delivered to tumors while simultaneously minimizing excess radiation to normal tissues. Safe and accurate delivery of radiation doses is critical to the ... ...

Abstract	Modern radiation therapy workflow involves complex processes intended to maximize the radiation dose delivered to tumors while simultaneously minimizing excess radiation to normal tissues. Safe and accurate delivery of radiation doses is critical to the successful execution of these treatment plans and effective treatment outcomes. Given extensive differences in existing dosimeters, the choice of devices and technologies for detecting biologically relevant doses of radiation has to be made judiciously, taking into account anatomical considerations and modality of treatment (invasive, e.g., interstitial brachytherapy vs noninvasive, e.g., external-beam therapy radiotherapy). Rapid advances in versatile radiation delivery technologies necessitate new detection platforms and devices that are readily adaptable into a multitude of form factors in order to ensure precision and safety in dose delivery. Here, we demonstrate the adaptability of radiation-responsive gel nanosensors as a platform technology for detecting ionizing radiation using three different form factors with an eye toward versatile use in the clinic. In this approach, ionizing radiation results in the reduction of monovalent gold salts leading to the formation of gold nanoparticles within gels formulated in different morphologies including one-dimensional (1D) needles for interstitial brachytherapy, two-dimensional (2D) area inserts for skin brachytherapy, and three-dimensional (3D) volumetric dose distribution in tissue phantoms. The formation of gold nanoparticles can be detected using distinct but complementary modes of readout including optical (visual) and photothermal detection, which further enhances the versatility of this approach. A linear response in the readout was seen as a function of radiation dose, which enabled straightforward calibration of each of these devices for predicting unknown doses of therapeutic relevance. Taken together, these results indicate that the gel nanosensor technology can be used to detect ionizing radiation in different morphologies and using different detection methods for application in treatment planning, delivery, and verification in radiotherapy and in trauma care.
MeSH term(s)	Gels ; Gold ; Metal Nanoparticles ; Phantoms, Imaging ; Radiation, Ionizing
Chemical Substances	Gels ; Gold (7440-57-5)
Language	English
Publishing date	2022-03-22
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.2c01019
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Emerging applications of exosomes in cancer therapeutics and diagnostics.

Inamdar, Sahil / Nitiyanandan, Rajeshwar / Rege, Kaushal

Bioengineering & translational medicine

2017 Volume 2, Issue 1, Page(s) 70–80

Abstract: Exosomes are nanoscale extracellular vesicles that are shed from different cells in the body. Exosomes encapsulate several biomolecules including lipids, proteins, and nucleic acids, and can therefore play a key role in cellular communication. These ... ...

Abstract	Exosomes are nanoscale extracellular vesicles that are shed from different cells in the body. Exosomes encapsulate several biomolecules including lipids, proteins, and nucleic acids, and can therefore play a key role in cellular communication. These vesicles can be isolated from different body fluids and their small sizes make them attractive in various biomedical applications. Here, we review state-of-the art approaches in exosome isolation and purification, and describe their potential use in cancer vaccines, drug delivery, and diagnostics.
Language	English
Publishing date	2017-04-03
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2380-6761
ISSN	2380-6761
DOI	10.1002/btm2.10059
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Article: Versatile Detection and Monitoring of Ionizing Radiation Treatment Using Radiation-Responsive Gel Nanosensors

Pushpavanam, Karthik / Dutta, Subhadeep / Inamdar, Sahil / Bista, Tomasz / Sokolowski, Thaddeus / Rapchak, Alek / Sadeghi, Amir / Sapareto, Stephen / Rege, Kaushal

ACS applied materials & interfaces. 2022 Mar. 22, v. 14, no. 13

2022

Abstract	Modern radiation therapy workflow involves complex processes intended to maximize the radiation dose delivered to tumors while simultaneously minimizing excess radiation to normal tissues. Safe and accurate delivery of radiation doses is critical to the successful execution of these treatment plans and effective treatment outcomes. Given extensive differences in existing dosimeters, the choice of devices and technologies for detecting biologically relevant doses of radiation has to be made judiciously, taking into account anatomical considerations and modality of treatment (invasive, e.g., interstitial brachytherapy vs noninvasive, e.g., external-beam therapy radiotherapy). Rapid advances in versatile radiation delivery technologies necessitate new detection platforms and devices that are readily adaptable into a multitude of form factors in order to ensure precision and safety in dose delivery. Here, we demonstrate the adaptability of radiation-responsive gel nanosensors as a platform technology for detecting ionizing radiation using three different form factors with an eye toward versatile use in the clinic. In this approach, ionizing radiation results in the reduction of monovalent gold salts leading to the formation of gold nanoparticles within gels formulated in different morphologies including one-dimensional (1D) needles for interstitial brachytherapy, two-dimensional (2D) area inserts for skin brachytherapy, and three-dimensional (3D) volumetric dose distribution in tissue phantoms. The formation of gold nanoparticles can be detected using distinct but complementary modes of readout including optical (visual) and photothermal detection, which further enhances the versatility of this approach. A linear response in the readout was seen as a function of radiation dose, which enabled straightforward calibration of each of these devices for predicting unknown doses of therapeutic relevance. Taken together, these results indicate that the gel nanosensor technology can be used to detect ionizing radiation in different morphologies and using different detection methods for application in treatment planning, delivery, and verification in radiotherapy and in trauma care.
Keywords	brachytherapy ; gels ; gold ; nanogold ; sensors (equipment)
Language	English
Dates of publication	2022-0322
Size	p. 14997-15007.
Publishing place	American Chemical Society
Document type	Article
ISSN	1944-8252
DOI	10.1021/acsami.2c01019
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Plasmonic gel nanocomposites for detection of high energy electrons.

Pushpavanam, Karthik / Inamdar, Sahil / Dutta, Subhadeep / Bista, Tomasz / Sokolowski, Thaddeus / Sapareto, Stephen / Rege, Kaushal

Journal of materials chemistry. B

2020 Volume 8, Issue 22, Page(s) 4930–4939

Abstract: Radiation therapy is a common treatment modality employed in the treatment of cancer. High energy photons are the primary source of radiation but when administered, they leave an exit dose resulting in radiation damage to the adjacent healthy tissues. To ...

Abstract	Radiation therapy is a common treatment modality employed in the treatment of cancer. High energy photons are the primary source of radiation but when administered, they leave an exit dose resulting in radiation damage to the adjacent healthy tissues. To overcome this, high energy electrons are employed in cases of skin cancer to minimize radiation induced toxicity. Despite these advances, measurement of delivered radiation remains a challenge due to limitations with existing dosimeters including labor intensive fabrication, complex read-out techniques and post-irradiation instability. To overcome these limitations, we have developed a novel colorimetric plasmonic gel nanocomposite for the detection of therapeutic levels of radiation delivered in electron beam therapy. The plasmonic nanocomposite consists of an agarose gel matrix encapsulating precursor gold ions, which are reduced to gold nanoparticles as a result of exposure to high energy electrons. The formation of gold nanoparticles renders a change in color to the agarose matrix, resulting in the formation of plasmonic gel nanocomposites. The intensity of the color formed exhibits a linear relation with the delivered electron dose, which can be quantified using absorbance spectroscopy. The plasmonic gel nanocomposites were able to detect doses employed in fractionated electron therapy, including in an anthropomorphic phantom used for planning radiation treatments in the clinic. Furthermore, the use of glutathione as a quenching agent facilitated qualitative and quantitative spatial mapping of the delivered dose. Our results indicate that the ease of fabrication, simplicity of detection and quantification using absorbance spectroscopy, determination of spatial dose profiles, and relatively low cost make the plasmonic gel nanocomposite technology attractive for detecting electron doses in the clinic.
MeSH term(s)	Colorimetry/instrumentation ; Electrons ; Gold/chemistry ; Humans ; Nanogels/chemistry ; Particle Size ; Phantoms, Imaging ; Sepharose/chemistry ; Skin Neoplasms/radiotherapy ; Surface Properties
Chemical Substances	Nanogels ; Gold (7440-57-5) ; Sepharose (9012-36-6)
Language	English
Publishing date	2020-04-11
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2702241-9
ISSN	2050-7518 ; 2050-750X
ISSN (online)	2050-7518
ISSN	2050-750X
DOI	10.1039/d0tb00241k
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Article ; Online: Inhibition of glycolysis in the presence of antigen generates suppressive antigen-specific responses and restrains rheumatoid arthritis in mice.

Mangal, Joslyn L / Inamdar, Sahil / Le, Tien / Shi, Xiaojian / Curtis, Marion / Gu, Haiwei / Acharya, Abhinav P

Biomaterials

2021 Volume 277, Page(s) 121079

Abstract: Dendritic cells (DCs) rely on glycolysis for their energy needs to induce pro-inflammatory antigen-specific immune responses. Therefore, inhibiting DC glycolysis, while presenting the self-antigen, may prevent pro-inflammatory antigen-specific immune ... ...

Abstract	Dendritic cells (DCs) rely on glycolysis for their energy needs to induce pro-inflammatory antigen-specific immune responses. Therefore, inhibiting DC glycolysis, while presenting the self-antigen, may prevent pro-inflammatory antigen-specific immune responses. Previously we demonstrated that microparticles with alpha-ketoglutarate (aKG) in the polymer backbone (paKG MPs) were able to generate anti-inflammatory DCs by sustained delivery of the aKG metabolite, and by modulating energy metabolism of DCs. Herein, we demonstrate that paKG MPs-based delivery of a glycolytic inhibitor, PFK15, using paKG MPs induces anti-inflammatory DCs (CD86
MeSH term(s)	Animals ; Arthritis, Experimental ; Arthritis, Rheumatoid/drug therapy ; Dendritic Cells ; Glycolysis ; Mice ; Mice, Inbred DBA ; Pyridines ; Quinolines
Chemical Substances	PFK15 ; Pyridines ; Quinolines
Language	English
Publishing date	2021-08-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2021.121079
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