@article{perry_tian_sengottuvel_harrison_gorentla_kapadia_cheng_luft_ting_desimone_et al._2020, title={Pulmonary Delivery of Nanoparticle-Bound Toll-like Receptor 9 Agonist for the Treatment of Metastatic Lung Cancer}, volume={14}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.0c02207}, abstractNote={CpG oligodeoxynucleotides (ODNs) are potent toll-like receptor (TLR) 9 agonists and have shown promise as anti-cancer agents in preclinical studies and clinical trials. Binding of CpG to TLR9 initiates a cascade of innate and adaptive immune responses, beginning with activation of dendritic cells, and resulting in a range of secondary effects that include the secretion of pro-inflammatory cytokines, activation of natural killer (NK) cells, and expansion of T cell populations. Recent literature suggests that local delivery of CpG in tumors results in superior antitumor effects as compared to systemic delivery. In this study, we utilized PRINT (particle replication in non-wetting templates) nanoparticles as a vehicle to deliver CpG into murine lungs through orotracheal instillations. In two orthotopic metastasis models of non-small cell lung cancer (NSCLC) - 344SQ (lung adenocarcinoma) and KAL-LN2E1 (lung squamous carcinoma), local delivery of PRINT-CpG into the lungs effectively promoted substantial tumor regression and also limited systemic toxicities associated with soluble CpG. Furthermore, cured mice were completely resistant to tumor re-challenge. Additionally, nano-delivery showed extended retention of CpG within the lungs as well as elevated anti-tumor cytokines. These results demonstrate that PRINT-CpG is a potent nanoplatform for local treatment of lung cancer that has collateral therapeutic effects on systemic disease, an encouraging toxicity profile, and may have the potential to treat lung metastasis of other cancer types.}, number={6}, journal={ACS NANO}, author={Perry, Jillian L. and Tian, Shaomin and Sengottuvel, Nisitha and Harrison, Emily B. and Gorentla, Balachandra K. and Kapadia, Chintan H. and Cheng, Ning and Luft, J. Christopher and Ting, Jenny P-Y and DeSimone, Joseph M. and et al.}, year={2020}, month={Jun}, pages={7200–7215} }
 @article{kapadia_tian_perry_luft_desimone_2019, title={Role of Linker Length and Antigen Density in Nanoparticle Peptide Vaccine}, volume={4}, ISSN={["2470-1343"]}, DOI={10.1021/acsomega.8b03391}, abstractNote={Multiple studies have been published emphasizing the significant role of nanoparticle (NP) carriers in antigenic peptide-based subunit vaccines for the induction of potent humoral and cellular responses. Various design parameters of nanoparticle subunit vaccines such as linker chemistry, the proximity of antigenic peptide to NPs, and the density of antigenic peptides on the surface of NPs play an important role in antigen presentation to dendritic cells (DCs) and in subsequent induction of CD8+ T cell response. In this current study, we evaluated the role of peptide antigen proximity and density on DC uptake, antigen cross-presentation, in vitro T cell proliferation, and in vivo induction of CD8+ T cells. To evaluate the role of antigen proximity, CSIINFEKL peptides were systematically conjugated to poly(ethylene glycol) (PEG) hydrogels through N-hydroxysuccinimide–PEG–maleimide linkers of varying molecular weights: 2k, 5k, and 10k. We observed that the peptides conjugated to NPs via the 2k and 5k PEG linkers resulted in higher uptake in bone marrow-derived DCs (BMDCs) and increased p-MHC-I formation on the surface of bone marrow-derived DCs (BMDCs) as compared to the 10k PEG linker formulation. However, no significant differences in vitro T cell proliferation and induction of in vivo CD8+ T cells were found among linker lengths. To study the effect of antigen density, CSIINFEKL peptides were conjugated to PEG hydrogels via 5k PEG linkers at various densities. We found that high antigen density NPs presented the highest p-MHC-I on the surface of BMDCs and induced higher proliferation of T cells, whereas NPs with low peptide density resulted in higher DC cell uptake and elevated frequency of IFN-γ producing CD8+ T cells in mice as compared to the medium- and high-density formulations. Altogether, findings for these experiments highlighted the importance of linker length and peptide antigen density on DC cell uptake, antigen presentation, and induction of in vivo CD8+ T cell response.}, number={3}, journal={ACS OMEGA}, author={Kapadia, Chintan H. and Tian, Shaomin and Perry, Jillian L. and Luft, J. Christopher and Desimone, Joseph M.}, year={2019}, month={Mar}, pages={5547–5555} }
 @article{merkel_jones_herlihy_kersey_shields_napier_luft_wu_zamboni_wang_et al._2011, title={Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles}, volume={108}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1010013108}, abstractNote={It has long been hypothesized that elastic modulus governs the biodistribution and circulation times of particles and cells in blood; however, this notion has never been rigorously tested. We synthesized hydrogel microparticles with tunable elasticity in the physiological range, which resemble red blood cells in size and shape, and tested their behavior in vivo. Decreasing the modulus of these particles altered their biodistribution properties, allowing them to bypass several organs, such as the lung, that entrapped their more rigid counterparts, resulting in increasingly longer circulation times well past those of conventional microparticles. An 8-fold decrease in hydrogel modulus correlated to a greater than 30-fold increase in the elimination phase half-life for these particles. These results demonstrate a critical design parameter for hydrogel microparticles.}, number={2}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Merkel, Timothy J. and Jones, Stephen W. and Herlihy, Kevin P. and Kersey, Farrell R. and Shields, Adam R. and Napier, Mary and Luft, J. Christopher and Wu, Huali and Zamboni, William C. and Wang, Andrew Z. and et al.}, year={2011}, month={Jan}, pages={586–591} }
 @article{gratton_ropp_pohlhaus_luft_madden_napier_desimone_2008, title={The effect of particle design on cellular internalization pathways}, volume={105}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.0801763105}, abstractNote={The interaction of particles with cells is known to be strongly influenced by particle size, but little is known about the interdependent role that size, shape, and surface chemistry have on cellular internalization and intracellular trafficking. We report on the internalization of specially designed, monodisperse hydrogel particles into HeLa cells as a function of size, shape, and surface charge. We employ a top-down particle fabrication technique called PRINT that is able to generate uniform populations of organic micro- and nanoparticles with complete control of size, shape, and surface chemistry. Evidence of particle internalization was obtained by using conventional biological techniques and transmission electron microscopy. These findings suggest that HeLa cells readily internalize nonspherical particles with dimensions as large as 3 μm by using several different mechanisms of endocytosis. Moreover, it was found that rod-like particles enjoy an appreciable advantage when it comes to internalization rates, reminiscent of the advantage that many rod-like bacteria have for internalization in nonphagocytic cells.}, number={33}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Gratton, Stephanie E. A. and Ropp, Patricia A. and Pohlhaus, Patrick D. and Luft, J. Christopher and Madden, Victoria J. and Napier, Mary E. and DeSimone, Joseph M.}, year={2008}, month={Aug}, pages={11613–11618} }