@article{vanblunk_srikanth_pandit_kuznetsov_brudno_2023, title={Absorption rate governs cell transduction in dry macroporous scaffolds}, volume={1}, ISSN={["2047-4849"]}, DOI={10.1039/d2bm01753a}, abstractNote={Dry, macroporous scaffolds efficiently transduce T cells, but the mechanism for this transduction has not been studied previously. We report that liquid volume and resultant differences in liquid absorption rates governs cell transduction efficiency.}, journal={BIOMATERIALS SCIENCE}, author={VanBlunk, Madelyn and Srikanth, Vishal and Pandit, Sharda S. and Kuznetsov, Andrey V. and Brudno, Yevgeny}, year={2023}, month={Jan} }
 @article{vanblunk_agarwalla_pandit_brudno_2022, title={Fabrication and Use of Dry Macroporous Alginate Scaffolds for Viral Transduction of T Cells}, volume={9}, ISSN={["1940-087X"]}, DOI={10.3791/64036}, abstractNote={Genetic engineering of T cells for CAR-T cell therapy has come to the forefront of cancer treatment over the last few years. CAR-T cells are produced by viral gene transfer into T cells. The current gold standard of viral gene transfer involves spinoculation of retronectin-coated plates, which is expensive and time-consuming. There is a significant need for efficient and cost-effective methods to generate CAR-T cells. Described here is a method for fabricating inexpensive, dry macroporous alginate scaffolds, known as Drydux scaffolds, that efficiently promote viral transduction of activated T cells. The scaffolds are designed to be used in place of gold standard spinoculation of retronectin-coated plates seeded with virus and simplify the process for transducing cells. Alginate is cross-linked with calcium-D-gluconate and frozen overnight to create the scaffolds. The frozen scaffolds are freeze-dried in a lyophilizer for 72 h to complete the formation of the dry macroporous scaffolds. The scaffolds mediate viral gene transfer when virus and activated T cells are seeded together on top of the scaffold to produce genetically modified cells. The scaffolds produce >85% primary T cell transduction, which is comparable to the transduction efficiency of spinoculation on retronectin-coated plates. These results demonstrate that dry macroporous alginate scaffolds serve as a cheaper and more convenient alternative to the conventional transduction method.}, number={187}, journal={JOVE-JOURNAL OF VISUALIZED EXPERIMENTS}, author={VanBlunk, Madelyn and Agarwalla, Pritha and Pandit, Sharda and Brudno, Yevgeny}, year={2022}, month={Sep} }
 @article{pandit_palvai_massaro_pierce_brudno_2022, title={Tissue-reactive drugs enable materials-free local depots}, volume={343}, ISSN={["1873-4995"]}, DOI={10.1016/j.jconrel.2022.01.023}, abstractNote={Local, sustained drug delivery of potent therapeutics holds promise for the treatment of a myriad of localized diseases while eliminating systemic side effects. However, introduction of drug delivery depots such as viscous hydrogels or polymer-based implants is highly limited in stiff tissues such as desmoplastic tumors. Here, we present a method to create materials-free intratumoral drug depots through Tissue-Reactive Anchoring Pharmaceuticals (TRAPs). TRAPs diffuse into tissue and attach locally for sustained drug release. In TRAPs, potent drugs are modified with ECM-reactive groups and then locally injected to quickly react with accessible amines within the ECM, creating local drug depots. We demonstrate that locally injected TRAPs create dispersed, stable intratumoral depots deep within mouse and human pancreatic tumor tissues. TRAPs depots based on ECM-reactive paclitaxel (TRAP paclitaxel) had better solubility than free paclitaxel and enabled sustained in vitro and in vivo drug release. TRAP paclitaxel induced higher tumoral apoptosis and sustained better antitumor efficacy than the free drug. By providing continuous drug access to tumor cells, this material-free approach to sustained drug delivery of potent therapeutics has the potential in a wide variety of diseases where current injectable depots fall short.}, journal={JOURNAL OF CONTROLLED RELEASE}, author={Pandit, Sharda and Palvai, Sandeep and Massaro, Nicholas P. and Pierce, Joshua G. and Brudno, Yevgeny}, year={2022}, month={Mar}, pages={142–151} }
 @article{palvai_moody_pandit_brudno_2021, title={On-Demand Drug Release from Click-Refillable Drug Depots}, volume={18}, ISSN={["1543-8392"]}, DOI={10.1021/acs.molpharmaceut.1c00535}, abstractNote={Stimuli-responsive, on-demand release of drugs from drug-eluting depots could transform the treatment of many local diseases, providing intricate control over local dosing. However, conventional on-demand drug release approaches rely on locally implanted drug depots, which become spent over time and cannot be refilled or reused without invasive procedures. New strategies to noninvasively refill drug-eluting depots followed by on-demand release could transform clinical therapy. Here we report an on-demand drug delivery paradigm that combines bioorthogonal click chemistry to locally enrich protodrugs at a prelabeled site and light-triggered drug release at the target tissue. This approach begins with introduction of the targetable depot through local injection of chemically reactive azide groups that anchor to the extracellular matrix. The anchored azide groups then capture blood-circulating protodrugs through bioorthogonal click chemistry. After local capture and retention, active drugs can be released through external light irradiation. In this report, a photoresponsive protodrug was constructed consisting of the chemotherapeutic doxorubicin (Dox), conjugated to dibenzocyclooctyne (DBCO) through a photocleavable ortho-nitrobenzyl linker. The protodrug exhibited excellent on-demand light-triggered Dox release properties and light-mediated in vitro cytotoxicity in U87 glioblastoma cell lines. Furthermore, in a live animal setting, azide depots formed in mice through intradermal injection of activated azide-NHS esters. After i.v. administration, the protodrug was captured by the azide depots with intricate local specificity, which could be increased with multiple refills. Finally, doxorubicin could be released from the depot upon light irradiation. Multiple rounds of depot refilling and light-mediated release of active drug were accomplished, indicating that this system has the potential for multiple rounds of treatment. Taken together, these in vitro and in vivo proof of concept studies establish a novel method for in vivo targeting and on-demand delivery of cytotoxic drugs at target tissues.}, number={10}, journal={MOLECULAR PHARMACEUTICS}, author={Palvai, Sandeep and Moody, Christopher T. and Pandit, Sharda and Brudno, Yevgeny}, year={2021}, month={Oct}, pages={3920–3925} }