Jenny Liu

A Convergent Synthetic Platform for Single-Nanoparticle Combination Cancer Therapy: Ratiometric Loading and Controlled Release of Cisplatin, Doxorubicin, and Camptothecin

The synthesis of polymer therapeutics capable of controlled loading and synchronized release of multiple therapeutic agents remains a formidable challenge in drug delivery and synthetic polymer chemistry. Herein, we report the synthesis of polymer nanoparticles (NPs) that carry precise molar ratios of doxorubicin, camptothecin, and cisplatin. To our knowledge, this work provides the first example of orthogonally triggered release of three drugs from single NPs. The highly convergent synthetic approach opens the door to new NP-based combination therapies for cancer.

Using an RNAi Signature Assay To Guide the Design of Three-Drug-Conjugated Nanoparticles with Validated Mechanisms, In Vivo Efficacy, and Low Toxicity

Single-nanoparticle (NP) combination chemotherapeutics are quickly emerging as attractive alternatives to traditional chemotherapy due to their ability to increase drug solubility, reduce off-target toxicity, enhance blood circulation lifetime, and increase the amount of drug delivered to tumors. In the case of NP-bound drugs, that is, NP-prodrugs, the current standard of practice is to assume that the subcellular mechanism of action for each drug released from the NP mirrors that of the unbound, free-drug. Here, we use an RNAi signature assay for the first time to examine the mechanism of action of multidrug-conjugated NP prodrugs relative to their small molecule prodrugs and native drug mechanisms of action. Additionally, the effective additive contribution of three different drugs in a single-NP platform is characterized. The results indicate that some platinum(IV) cisplatin prodrugs, although cytotoxic, may not have the expected mechanism of action for cisplatin. This insight was utilized to develop a novel platinum(IV) oxaliplatin prodrug and incorporate it into a three-drug-conjugated NP, where each drugs mechanism of action is preserved, to treat tumor-bearing mice with otherwise lethal levels of chemotherapy.

STEM Education

This position paper discusses the use of the Zero Robotics Summer Program competition as a tool to teach programing to students in middle school (ages 11-14). The benefits of teaching programing at that age are discussed, including grasping the student attention early on and providing a useful skill. Zero Robotics is a free programming competition where students program microsatellites to compete with other studentprogrammed satellites in a virtual game using an online simulation. The finalists see their code compete on the SPHERES satellites aboard the International Space Station, during a final competition transmitted live. The game and curriculum teaches students physics, mathematics, and programming concepts. This position paper argues that it is possible to engage students in programing by providing the right incentive (space) through a competitive environment where teachers have a curriculum to back them up, without becoming a standard classroom exercise.

Classification of hospital acquired complications using temporal clinical information from a large electronic health record

Hospital acquired complications (HACs) are serious problems affecting modern day healthcare institutions. It is estimated that HACs result in an approximately 10% increase in total inpatient hospital costs across US hospitals. With US hospital spending totaling nearly

Reduction of liver fibrosis by rationally designed macromolecular telmisartan prodrugs

900 billion per annum, the damages caused by HACs are no small matter. Early detection and prevention of HACs could greatly reduce strains on the US healthcare system and improve patient morbidity & mortality rates. Here, we describe a machine-learning model for predicting the occurrence of HACs within five distinct categories using temporal clinical data. Using our approach, we find that at least

Students touch space in Zero Robotics programming competition with free downloadable curriculum

10 billion of excessive hospital costs could be saved in the US alone, with the institution of effective preventive measures. In addition, we also identify several keystone features that demonstrate high predictive power for HACs over different time periods following patient admission. The classifiers and features analyzed in this study show high promise of being able to be used for accurate prediction of HACs in clinical settings, and furthermore provide novel insights into the contribution of various clinical factors to the risk of developing HACs as a function of healthcare system exposure.

“Brush-First” Method for the Parallel Synthesis of Photocleavable, Nitroxide-Labeled Poly(ethylene glycol) Star Polymers

At present there are no drugs for the treatment of chronic liver fibrosis that have been approved by the Food and Drug Administration of the United States. Telmisartan, a small-molecule antihypertensive drug, displays antifibrotic activity, but its clinical use is limited because it causes systemic hypotension. Here, we report the scalable and convergent synthesis of macromolecular telmisartan prodrugs optimized for preferential release in diseased liver tissue. We have optimized the release of active telmisartan in fibrotic liver to be depot-like (that is, a constant therapeutic concentration) through the molecular design of telmisartan brush-arm star polymers, and show that these lead to improved efficacy and to the avoidance of dose-limiting hypotension in both metabolically and chemically induced mouse models of hepatic fibrosis, as determined by histopathology, enzyme levels in the liver, intact-tissue protein markers, hepatocyte necrosis protection and gene-expression analyses. In rats and dogs, the prodrugs are retained long term in liver tissue, and have a well-tolerated safety profile. Our findings support the further development of telmisartan prodrugs that enable infrequent dosing in the treatment of liver fibrosis.Macromolecular telmisartan prodrugs optimized for preferential release in fibrotic liver tissue reduce liver fibrosis in mouse models, and are retained and well tolerated in the liver tissue of rats and dogs.

Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats.

This paper describes the free downloadable curriculum for the first national Zero Robotics Middle School programming competition where student code is uploaded to the International Space Station for a final competition refereed by astronauts with live video feed. The curriculum includes both printed and online content, and has been implemented this past summer as part of the Zero Robotics Middle School Summer Program 2013. Students who attended the programs reported significantly higher scores related to understanding of: (1) Research on the International Space Station National Laboratory, (2) The uniqueness of the research environment on the International Space Station and (3) Possible careers related to robotics. Over 90% of students reported that they would recommend Zero Robotics to a friend. The pilot Zero Robotics Middle School program has achieved its goal of leveraging the resources of SPHERES as a tool for Science, Technology Engineering and Math education, and plans to expand the program further next summer.