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Article ; Online: Dynamic bioinspired coculture model for probing ER

Pradhan, Lina / Moore, DeVonte / Ovadia, Elisa M / Swedzinski, Samantha L / Cossette, Travis / Sikes, Robert A / van Golen, Kenneth / Kloxin, April M

Science advances

2023 Volume 9, Issue 10, Page(s) eade3186

Abstract: Late recurrences of breast cancer are hypothesized to arise from disseminated tumor cells (DTCs) that reactivate after dormancy and occur most frequently with estrogen receptor-positive ( ... ...

Abstract	Late recurrences of breast cancer are hypothesized to arise from disseminated tumor cells (DTCs) that reactivate after dormancy and occur most frequently with estrogen receptor-positive (ER
MeSH term(s)	Humans ; Female ; Breast Neoplasms/metabolism ; Coculture Techniques ; Bone Marrow/pathology ; Signal Transduction ; Cell Communication ; Tumor Microenvironment
Language	English
Publishing date	2023-03-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.ade3186
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Article ; Online: Injectable liposome-containing click hydrogel microparticles for release of macromolecular cargos.

Palmese, Luisa L / LeValley, Paige J / Pradhan, Lina / Parsons, Amanda L / Oakey, John S / Abraham, Mathew / D'Addio, Suzanne M / Kloxin, April M / Liang, Yingkai / Kiick, Kristi L

Soft matter

2024 Volume 20, Issue 8, Page(s) 1736–1745

Abstract: Hydrogel microparticles ranging from 0.1-100 μm, referred to as microgels, are attractive for biological applications afforded by their injectability and modularity, which allows facile delivery of mixed populations for tailored combinations of ... ...

Abstract	Hydrogel microparticles ranging from 0.1-100 μm, referred to as microgels, are attractive for biological applications afforded by their injectability and modularity, which allows facile delivery of mixed populations for tailored combinations of therapeutics. Significant efforts have been made to broaden methods for microgel production including
MeSH term(s)	Animals ; Horses ; Hydrogels/chemistry ; Liposomes ; Microgels ; Microfluidics ; Rheology
Chemical Substances	Hydrogels ; Liposomes ; Microgels
Language	English
Publishing date	2024-02-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2191476-X
ISSN	1744-6848 ; 1744-683X
ISSN (online)	1744-6848
ISSN	1744-683X
DOI	10.1039/d3sm01009k
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Article ; Online: Destructive fibrotic teamwork: how both microenvironment stiffness and profibrotic interleukin 13 impair alveolar macrophage phenotype and function.

Bomb, Kartik / Pradhan, Lina / Zhang, Qi / Jarai, Bader M / Bhattacharjee, Arnab / Burris, David L / Kloxin, April M / Fromen, Catherine A

Biomaterials science

2022 Volume 10, Issue 19, Page(s) 5689–5706

Abstract: The pulmonary fibrotic microenvironment is characterized by increased stiffness of lung tissue and enhanced secretion of profibrotic soluble cues contributing to a feedback loop that leads to dysregulated wound healing and lung failure. Pinpointing the ... ...

Abstract	The pulmonary fibrotic microenvironment is characterized by increased stiffness of lung tissue and enhanced secretion of profibrotic soluble cues contributing to a feedback loop that leads to dysregulated wound healing and lung failure. Pinpointing the individual and tandem effects of profibrotic stimuli in impairing immune cell response remains difficult and is needed for improved therapeutic strategies. We utilized a statistical design of experiment (DOE) to investigate how microenvironment stiffness and interleukin 13 (IL13), a profibrotic soluble factor linked with disease severity, contribute to the impaired macrophage response commonly observed in pulmonary fibrosis. We used engineered bioinspired hydrogels of different stiffness, ranging from healthy to fibrotic lung tissue, and cultured murine alveolar macrophages (MH-S cells) with or without IL13 to quantify cell response and analyze independent and synergistic effects. We found that, while both stiffness and IL13 independently influence macrophage morphology, phenotype, phagocytosis and efferocytosis, these factors work synergistically to exacerbate impaired macrophage phenotype and efferocytosis. These unique findings provide insights into how macrophages in fibrotic conditions are not as effective in clearing debris, contributing to fibrosis initiation/progression, and more broadly inform how underlying drivers of fibrosis modulate immune cell response to facilitate therapeutic strategies.
MeSH term(s)	Animals ; Fibrosis ; Hydrogels/therapeutic use ; Interleukin-13/therapeutic use ; Macrophages, Alveolar/pathology ; Mice ; Phenotype ; Pulmonary Fibrosis/chemically induced
Chemical Substances	Hydrogels ; Interleukin-13
Language	English
Publishing date	2022-09-27
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/d2bm00828a
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Article: Destructive fibrotic teamwork: how both microenvironment stiffness and profibrotic interleukin 13 impair alveolar macrophage phenotype and function

Bomb, Kartik / Pradhan, Lina / Zhang, Qi / Jarai, Bader M. / Bhattacharjee, Arnab / Burris, David L. / Kloxin, April M. / Fromen, Catherine A.

Biomaterials science. 2022 Sept. 27, v. 10, no. 19

2022

Abstract	The pulmonary fibrotic microenvironment is characterized by increased stiffness of lung tissue and enhanced secretion of profibrotic soluble cues contributing to a feedback loop that leads to dysregulated wound healing and lung failure. Pinpointing the individual and tandem effects of profibrotic stimuli in impairing immune cell response remains difficult and is needed for improved therapeutic strategies. We utilized a statistical design of experiment (DOE) to investigate how microenvironment stiffness and interleukin 13 (IL13), a profibrotic soluble factor linked with disease severity, contribute to the impaired macrophage response commonly observed in pulmonary fibrosis. We used engineered bioinspired hydrogels of different stiffness, ranging from healthy to fibrotic lung tissue, and cultured murine alveolar macrophages (MH-S cells) with or without IL13 to quantify cell response and analyze independent and synergistic effects. We found that, while both stiffness and IL13 independently influence macrophage morphology, phenotype, phagocytosis and efferocytosis, these factors work synergistically to exacerbate impaired macrophage phenotype and efferocytosis. These unique findings provide insights into how macrophages in fibrotic conditions are not as effective in clearing debris, contributing to fibrosis initiation/progression, and more broadly inform how underlying drivers of fibrosis modulate immune cell response to facilitate therapeutic strategies.
Keywords	biocompatible materials ; disease severity ; fibrosis ; hydrogels ; interleukin-13 ; lungs ; macrophages ; mice ; phagocytosis ; phenotype ; pulmonary fibrosis ; secretion ; teams ; therapeutics
Language	English
Dates of publication	2022-0927
Size	p. 5689-5706.
Publishing place	The Royal Society of Chemistry
Document type	Article
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d2bm00828a
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Article: Polymer Stabilized Fe3O4-Graphene as an Amphiphilic Drug Carrier for Thermo-Chemotherapy of Cancer

Swain, Akshaya Kumar / Bahadur Dhirendra / Pradhan Lina

ACS Applied Materials & Interfaces. 2015 Apr. 22, v. 7, no. 15

2015

Abstract: In light of the growing interest in the search for cheap and effective solutions for cancer treatment, we report a simple one pot synthesis of polymer stabilized iron oxide-graphene (PIG) that could be realized on a large scale. The structural (FeâOâ ...

Abstract	In light of the growing interest in the search for cheap and effective solutions for cancer treatment, we report a simple one pot synthesis of polymer stabilized iron oxide-graphene (PIG) that could be realized on a large scale. The structural (FeâOâ particle size of â¼11 nm), functional (various oxygen containing moieties), and magnetic (moment of â¼43 emu/g) properties of PIG are explored using various characterization techniques for possible biomedical applications. PIG shows good colloidal stability and is biocompatible even at higher concentrations (2.5 mg/mL) by virtue of cross-linking polymers. The biocompatibility of the composite has been tested using HeLa cell lines by computing the percentage of the reactive oxygen species through the 2,7-dichlorofluorescein (DCF) intensity level. PIG has the ability to load and release both hydrophobic and hydrophilic drugs with a good loading efficiency and capacity. The dug loading efficiency of PIG is measured to be â¼87% and â¼91% for doxorubicin (DOX) and paclitaxel (PTXL), respectively. Under an AC magnetic field, superparamagnetic PIG (2.5 mg/mL) takes less than 16 min to reach the stable hyperthermia temperature, suggesting it as a good anticancer material. A time-dependent cellular uptake of doxorubicin-conjugated PIG has been studied to optimize the parameters for thermo-chemotherapy of cancer. The synergetic effect of both the drug and hyperthermia is observed in the killing of the cancerous cells, verified by computing the cell apoptotic population using a flow cytometer. However, it has been noticed that, even in the absence of chemotherapy, PIG shows good antiproliferative activity with thermotherapy alone.
Keywords	apoptosis ; biocompatibility ; crosslinking ; doxorubicin ; drug carriers ; drug therapy ; fever ; flow cytometry ; hydrophilicity ; hydrophobicity ; iron ; iron oxides ; magnetic fields ; neoplasms ; oxygen ; paclitaxel ; particle size ; polymers ; reactive oxygen species ; synergism ; thermotherapy
Language	English
Dates of publication	2015-0422
Size	p. 8013-8022.
Publishing place	American Chemical Society
Document type	Article
ISSN	1944-8252
DOI	10.1021%2Facsami.5b02536
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Article ; Online: Enhanced cell apoptosis triggered by a multi modal mesoporous amphiphilic drug delivery system.

Pradhan, Lina / Srivastava, R / Bahadur, D

Nanotechnology

2015 Volume 26, Issue 47, Page(s) 475101

Abstract: Mesoporous magnetic nanoparticles (MMNPs) have been synthesized through a facile soft chemical route and are conjugated with multiple therapeutic agents. These MMNPs have the ability to contain and deliver both hydrophilic and hydrophobic drugs ... ...

Abstract	Mesoporous magnetic nanoparticles (MMNPs) have been synthesized through a facile soft chemical route and are conjugated with multiple therapeutic agents. These MMNPs have the ability to contain and deliver both hydrophilic and hydrophobic drugs simultaneously with the mediation of an AC magnetic field (ACMF). Furthermore, the synthesis and characterization of doxorubicin hydrochloride:paclitaxel (DOX:TXL) and doxorubicin hydrochloride:cisplatin (DOX:Cis-Pt) conjugates are demonstrated. MMNPs show an excellent loading efficiency of ~96:83% (DOX:TXL) and ~93:83% (DOX:Cis-Pt) along with a loading capacity of ~0.002:0.002 mg mg(-1) (DOX:TXL) and ~0.002:0.002 mg mg(-1) (DOX:Cis-Pt), respectively. Over a period of 180 h, a sustained release of drugs is observed and shows a better efficiency at pH 4.3 (~85:63%-DOX:TXL and ~86:73%-DOX:Cis-Pt) compared to that under physiological pH conditions (~28:22%-DOX:TXL and ~26:22%-DOX:Cis-Pt). The MMNPs can release ~37:22% (DOX:TXL) and ~34:25% (DOX:Cis-Pt) within 30 min when triggered by an ACMF (at ~43 °C). The in vitro cytotoxic effect, the ROS generation level and cell cycle distribution analysis of DOX:TXL-MMNPs and DOX:Cis-Pt-MMNPs treated MDA-MB231, MCF-7 and PC3 cancer cells are demonstrated. Enhanced cell apoptosis is observed by thermo-chemotherapy which includes application of an ACMF for 15 min. Specifically, DOX:TXL-MMNPs are more effective than DOX:Cis-Pt-MMNPs towards the PC3 cell line. The internalization of multiple drug loaded MMNPs by cells and their morphological changes due to thermo-chemotherapy are confirmed through confocal microscopy. From the present results, it is observed that the DOX:TXL and DOX:Cis-Pt conjugated MMNPs, under an ACMF, can readily minimize drug resistance. This has significantly enhanced the cell apoptosis of target cancer cells.
MeSH term(s)	Apoptosis/drug effects ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Doxorubicin/pharmacokinetics ; Drug Delivery Systems/methods ; Humans ; MCF-7 Cells ; Magnetic Fields ; Magnetite Nanoparticles/chemistry ; Magnetite Nanoparticles/ultrastructure ; Nanoconjugates/chemistry ; Paclitaxel/pharmacokinetics ; Porosity ; Surface-Active Agents
Chemical Substances	Magnetite Nanoparticles ; Nanoconjugates ; Surface-Active Agents ; Doxorubicin (80168379AG) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2015-11-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1362365-5
ISSN	1361-6528 ; 0957-4484
ISSN (online)	1361-6528
ISSN	0957-4484
DOI	10.1088/0957-4484/26/47/475101
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Article ; Online: Polymer Stabilized Fe3O4-Graphene as an Amphiphilic Drug Carrier for Thermo-Chemotherapy of Cancer.

Swain, Akshaya Kumar / Pradhan, Lina / Bahadur, Dhirendra

ACS applied materials & interfaces

2015 Volume 7, Issue 15, Page(s) 8013–8022

Abstract	In light of the growing interest in the search for cheap and effective solutions for cancer treatment, we report a simple one pot synthesis of polymer stabilized iron oxide-graphene (PIG) that could be realized on a large scale. The structural (Fe3O4 particle size of ∼11 nm), functional (various oxygen containing moieties), and magnetic (moment of ∼43 emu/g) properties of PIG are explored using various characterization techniques for possible biomedical applications. PIG shows good colloidal stability and is biocompatible even at higher concentrations (2.5 mg/mL) by virtue of cross-linking polymers. The biocompatibility of the composite has been tested using HeLa cell lines by computing the percentage of the reactive oxygen species through the 2,7-dichlorofluorescein (DCF) intensity level. PIG has the ability to load and release both hydrophobic and hydrophilic drugs with a good loading efficiency and capacity. The dug loading efficiency of PIG is measured to be ∼87% and ∼91% for doxorubicin (DOX) and paclitaxel (PTXL), respectively. Under an AC magnetic field, superparamagnetic PIG (2.5 mg/mL) takes less than 16 min to reach the stable hyperthermia temperature, suggesting it as a good anticancer material. A time-dependent cellular uptake of doxorubicin-conjugated PIG has been studied to optimize the parameters for thermo-chemotherapy of cancer. The synergetic effect of both the drug and hyperthermia is observed in the killing of the cancerous cells, verified by computing the cell apoptotic population using a flow cytometer. However, it has been noticed that, even in the absence of chemotherapy, PIG shows good antiproliferative activity with thermotherapy alone.
MeSH term(s)	Antimetabolites, Antineoplastic/administration & dosage ; Antimetabolites, Antineoplastic/chemistry ; Cell Line, Tumor ; Diffusion ; Doxorubicin/administration & dosage ; Doxorubicin/chemistry ; Drug Stability ; Excipients/chemistry ; Graphite/chemistry ; Humans ; Magnetite Nanoparticles/chemistry ; Nanocapsules/administration & dosage ; Nanocapsules/chemistry ; Nanocapsules/ultrastructure ; Neoplasms, Experimental/drug therapy ; Neoplasms, Experimental/pathology ; Photochemotherapy/methods ; Photosensitizing Agents/chemistry ; Photosensitizing Agents/therapeutic use ; Surface-Active Agents/chemistry ; Treatment Outcome
Chemical Substances	Antimetabolites, Antineoplastic ; Excipients ; Magnetite Nanoparticles ; Nanocapsules ; Photosensitizing Agents ; Surface-Active Agents ; Graphite (7782-42-5) ; Doxorubicin (80168379AG)
Language	English
Publishing date	2015-04-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.5b02536
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Article ; Online: Assessing Therapeutic Potential of Magnetic Mesoporous Nanoassemblies for Chemo-Resistant Tumors.

Pradhan, Lina / Thakur, Bhushan / Srivastava, Rohit / Ray, Pritha / Bahadur, Dhirendra

Theranostics

2016 Volume 6, Issue 10, Page(s) 1557–1572

Abstract: Smart drug delivery system with strategic drug distribution is the future state-of-the-art treatment for any malignancy. To investigate therapeutic potential of such nanoparticle mediated delivery system, we examined the efficacy of dual drug-loaded, pH ... ...

Abstract	Smart drug delivery system with strategic drug distribution is the future state-of-the-art treatment for any malignancy. To investigate therapeutic potential of such nanoparticle mediated delivery system, we examined the efficacy of dual drug-loaded, pH and thermo liable lipid coated mesoporous iron oxide-based magnetic nanoassemblies (DOX:TXL-LMMNA) in mice bearing both drug sensitive (A2780(S)) and drug resistant (A2780-CisR) ovarian cancer tumor xenografts. In presence of an external AC magnetic field (ACMF), DOX:TXL-LMMNA particles disintegrate to release encapsulated drug due to hyperthermic temperatures (41-45 ºC). In vivo bio distribution study utilizing the optical and magnetic properties of DOX:TXL-LMMNA particles demonstrated minimum organ specific toxicity. Noninvasive bioluminescence imaging of mice bearing A2780(S) tumors and administered with DOX-TXL-LMMNA followed by the application of ACMF revealed 65% less luminescence signal and 80% mice showed complete tumor regression within eight days. A six months follow-up study revealed absence of relapse in 70% of the mice. Interestingly, the A2780-CisR tumors which did not respond to drug alone (DOX:TXL) showed 80% reduction in luminescence and tumor volume with DOX:TXL-LMMNA after thermo-chemotherapy within eight days. Cytotoxic effect of DOX:TXL-LMMNA particles was more pronounced in A2780-CisR cells than in their sensitive counterpart. Thus these novel stimuli sensitive nanoassemblies hold great promise for therapy resistant malignancies and future clinical applications.
MeSH term(s)	Animals ; Antineoplastic Agents/administration & dosage ; Disease Models, Animal ; Doxorubicin/administration & dosage ; Drug Carriers/administration & dosage ; Drug Resistance ; Female ; Heterografts ; Magnetite Nanoparticles/administration & dosage ; Mice ; Ovarian Neoplasms/drug therapy ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Drug Carriers ; Magnetite Nanoparticles ; Doxorubicin (80168379AG)
Language	English
Publishing date	2016-06-18
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592097-2
ISSN	1838-7640 ; 1838-7640
ISSN (online)	1838-7640
ISSN	1838-7640
DOI	10.7150/thno.15231
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Article ; Online: pH- and thermosensitive thin lipid layer coated mesoporous magnetic nanoassemblies as a dual drug delivery system towards thermochemotherapy of cancer.

Pradhan, Lina / Srivastava, R / Bahadur, D

Acta biomaterialia

2014 Volume 10, Issue 7, Page(s) 2976–2987

Abstract: A new pH-sensitive and thermosensitive dual drug delivery system consisting of thin lipid layer encapsulated mesoporous magnetite nanoassemblies (MMNA) has been developed which can deliver two anticancer drugs simultaneously. The formulation of lipid ... ...

Abstract	A new pH-sensitive and thermosensitive dual drug delivery system consisting of thin lipid layer encapsulated mesoporous magnetite nanoassemblies (MMNA) has been developed which can deliver two anticancer drugs simultaneously. The formulation of lipid layer used is 5:2:2:2 w/w, DPPC:cholesterol:DSPE-PEG2000:MMNA. The structure, morphology and magnetic properties of MMNA and lipid coated MMNA (LMMNA) were thoroughly characterized. This hybrid system was investigated for its ability to carry two anticancer drugs as well as its ability to provide heat under an alternating current magnetic field (ACMF). A very high loading efficiency of up to ∼81% of doxorubicin hydrochloride (DOX) with an ∼0.02 mg mg(-1) loading capacity and ∼60% of paclitaxel (TXL) with an ∼0.03 mg mg(-1) loading capacity are obtained with LMMNA. A sustained release of drug is observed over a period of 172 h, with better release, of ∼88:53% (DOX:TXL), at pH 4.3 compared to the ∼28:26% (DOX:TXL) in physiological conditions (pH 7.4). An enhanced release of ∼72 and ∼68% is recorded for DOX and TXL, respectively, during the first hour with the application of an ACMF (∼43°C). A greater in vitro cytotoxic effect is observed with the two drugs compared to them individually in HeLa, MCF-7 and HepG2 cancer cells. With the application of an ACMF for 10 min, the cell killing efficiency is improved substantially due to simultaneous thermo- and chemotherapy. Confocal microscopy confirms the internalization of drug loaded MMNA and LMMNA by cells and their morphological changes during thermochemotherapy.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Combined Modality Therapy ; Doxorubicin/administration & dosage ; Drug Delivery Systems ; Humans ; Hydrogen-Ion Concentration ; Lipids/chemistry ; Magnetics ; Microscopy, Atomic Force ; Microscopy, Electron, Transmission ; Neoplasms/drug therapy ; Neoplasms/therapy ; X-Ray Diffraction
Chemical Substances	Antineoplastic Agents ; Lipids ; Doxorubicin (80168379AG)
Language	English
Publishing date	2014-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2014.04.011
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Article: Efficient synthesis of rice based graphene quantum dots and their fluorescent properties

Kalita, Hemen / Mohapatra, Jeotikanta / Pradhan, Lina / Mitra, Arijit / Bahadur, Dhirendra / Aslam, Mohammed

RSC advances. 2016 Mar. 01, v. 6, no. 28

2016

Abstract: We present a facile green approach to synthesize monodisperse graphene quantum dots (GQDs) of sizes 2–6.5 nm using rice grains as a carbon source. As the size of the GQDs increases from 2–6.5 nm, a red shift (blue to cyan) in the photoluminescence ... ...

Abstract	We present a facile green approach to synthesize monodisperse graphene quantum dots (GQDs) of sizes 2–6.5 nm using rice grains as a carbon source. As the size of the GQDs increases from 2–6.5 nm, a red shift (blue to cyan) in the photoluminescence emission spectra is observed due to quantum confinement effect. The colloidal solution of as synthesized GQDs is highly luminescent under 336 nm illumination. The quantum yield (QY) of the as-prepared GQDs in water is size dependent and increases from 16 to 24% with the decrease in size from 6.5 to 2 nm. The potential of these GQDs as biomarkers for cell imaging is explored further. The cytoxicity study with different concentrations of the GQDs confirms the excellent biocompatibility of the GQDs.
Keywords	biocompatibility ; biomarkers ; fluorescence ; graphene ; image analysis ; lighting ; photoluminescence ; quantum dots ; rice
Language	English
Dates of publication	2016-0301
Size	p. 23518-23524.
Publishing place	The Royal Society of Chemistry
Document type	Article
ISSN	2046-2069
DOI	10.1039/c5ra25706a
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