@article{fromen_rahhal_robbins_kai_shen_luft_desimone_2016, title={Nanoparticle surface charge impacts distribution, uptake and lymph node trafficking by pulmonary antigen-presenting cells}, volume={12}, ISSN={["1549-9642"]}, DOI={10.1016/j.nano.2015.11.002}, abstractNote={Engineered nanoparticles have the potential to expand the breadth of pulmonary therapeutics, especially as respiratory vaccines. Notably, cationic nanoparticles have been demonstrated to produce superior local immune responses following pulmonary delivery; however, the cellular mechanisms of this increased response remain unknown. To this end, we investigated the cellular response of lung APCs following pulmonary instillation of anionic and cationic charged nanoparticles. While nanoparticles of both surface charges were capable of trafficking to the draining lymph node and were readily internalized by alveolar macrophages, both CD11b and CD103 lung dendritic cell (DC) subtypes preferentially associated with cationic nanoparticles. Instillation of cationic nanoparticles resulted in the upregulation of Ccl2 and Cxc10, which likely contributes to the recruitment of CD11b DCs to the lung. In total, these cellular mechanisms explain the increased efficacy of cationic formulations as a pulmonary vaccine carrier and provide critical benchmarks in the design of pulmonary vaccine nanoparticles.Advance in nanotechnology has allowed the production of precise nanoparticles as vaccines. In this regard, pulmonary delivery has the most potential. In this article, the authors investigated the interaction of nanoparticles with various types of lung antigen presenting cells in an attempt to understand the cellular mechanisms. The findings would further help the future design of much improved vaccines for clinical use.}, number={3}, journal={NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE}, author={Fromen, Catherine A. and Rahhal, Tojan B. and Robbins, Gregory R. and Kai, Marc P. and Shen, Tammy W. and Luft, J. Christopher and DeSimone, Joseph M.}, year={2016}, month={Apr}, pages={677–687} }
 @article{kai_brighton_fromen_shen_luft_luft_keeler_robbins_ting_zamboni_et al._2016, title={Tumor Presence Induces Global Immune Changes and Enhances Nanoparticle Clearance}, volume={10}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.5b05999}, abstractNote={Long-circulating nanoparticles are essential for increasing tumor accumulation to provide therapeutic efficacy. While it is known that tumor presence can alter the immune system, very few studies have explored this impact on nanoparticle circulation. In this report, we demonstrate how the presence of a tumor can change the local and global immune system, which dramatically increases particle clearance. We found that tumor presence significantly increased clearance of PRINT hydrogel nanoparticles from the circulation, resulting in increased accumulation in the liver and spleen, due to an increase in M2-like macrophages. Our findings highlight the need to better understand interactions between immune status and nanoparticle clearance, and suggest that further consideration of immune function is required for success in preclinical and clinical nanoparticle studies.}, number={1}, journal={ACS NANO}, author={Kai, Marc P. and Brighton, Hailey E. and Fromen, Catherine A. and Shen, Tammy W. and Luft, J. Christopher and Luft, Yancey E. and Keeler, Amanda W. and Robbins, Gregory R. and Ting, Jenny P. Y. and Zamboni, William C. and et al.}, year={2016}, month={Jan}, pages={861–870} }
 @article{fromen_robbins_shen_kai_ting_desimone_2015, title={Controlled analysis of nanoparticle charge on mucosal and systemic antibody responses following pulmonary immunization}, volume={112}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1422923112}, abstractNote={Significance}, number={2}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Fromen, Catherine A. and Robbins, Gregory R. and Shen, Tammy W. and Kai, Marc P. and Ting, Jenny P. Y. and DeSimone, Joseph M.}, year={2015}, month={Jan}, pages={488–493} }
 @article{shen_fromen_kai_luft_rahhal_robbins_desimone_2015, title={Distribution and Cellular Uptake of PEGylated Polymeric Particles in the Lung Towards Cell-Specific Targeted Delivery}, volume={32}, ISSN={0724-8741 1573-904X}, url={http://dx.doi.org/10.1007/s11095-015-1701-7}, DOI={10.1007/s11095-015-1701-7}, abstractNote={We evaluated the role of a poly(ethylene glycol) (PEG) surface coating to increase residence times and alter the cellular fate of nano- and microparticles delivered to the lung.Three sizes of PRINT hydrogel particles (80 × 320 nm, 1.5 and 6 μm donuts) with and without a surface PEG coating were instilled in the airways of C57/b6 mice. At time points of 1, 7, and 28 days, BALF and whole lungs were evaluated for the inflammatory cytokine Il-6 and chemokine MIP-2, histopathology, cellular populations of macrophages, dendritic cells (DCs), and granulocytes, and particulate uptake within these cells through flow cytometry, ELISAs, and fluorescent imaging.Particles of all sizes and surface chemistries were readily observed in the lung with minimal inflammatory response at all time points. Surface modification with PEGylation was found to significantly increase lung residence times and homogeneous lung distribution, delaying macrophage clearance of all sizes, with the largest increase in residence time observed for 80 × 320 nm particles. Additionally, it was observed that DCs were recruited to the airway following administration of unPEGylated particles and preferentially associated with these particles.Pulmonary drug delivery vehicles designed with a PEG surface coating can be used to delay particle uptake and promote cell-specific targeting of therapeutics.}, number={10}, journal={Pharmaceutical Research}, publisher={Springer Science and Business Media LLC}, author={Shen, Tammy W. and Fromen, Catherine A. and Kai, Marc P. and Luft, J. Christopher and Rahhal, Tojan B. and Robbins, Gregory R. and DeSimone, Joseph M.}, year={2015}, month={May}, pages={3248–3260} }
 @article{fromen_shen_larus_mack_maynor_luft_desimone_2013, title={Synthesis and characterization of monodisperse uniformly shaped respirable aerosols}, volume={59}, ISSN={["1547-5905"]}, DOI={10.1002/aic.14157}, abstractNote={The top‐down, micromolding technique, referred to as Particle Replication in Nonwetting Templates (PRINT®), affords a new opportunity for the generation of inhalation therapeutics. Powders were fabricated with predetermined particle size and shape; when dispersed with a collision jet nebulizer, these particles resulted in monodisperse aerosols with geometric standard deviations well below 1.2. Dynamic shape factors for this novel set of uniformly shaped particles were determined by correcting the drag of nonspherical particles in the ultra‐Stokesian flow conditions of the aerodynamic particle sizer (APS). This convenient approach for shape factor determination agreed well with current literature approaches and allowed for the correction of APS results for particles with known volumes. Determined shape factor values of PRINT geometries were used to estimate the theoretical median aerodynamic diameters of individual aerosols, which were then compared to actual inhalation powders. © 2013 American Institute of Chemical Engineers AIChE J, 59: 3184–3194, 2013}, number={9}, journal={AICHE JOURNAL}, author={Fromen, Catherine A. and Shen, Tammy W. and Larus, Abigail E. and Mack, Peter and Maynor, Benjamin W. and Luft, J. Christopher and DeSimone, Joseph M.}, year={2013}, month={Sep}, pages={3184–3194} }