Dr. Khalifehzadeh received a dual Ph.D. in Chemical Engineering and Nanotechnology & Molecular Engineering from the University of Washington (UW) in 2018. Her thesis research was focused on design of new classes of degradable polymers for the next generation of cardiovascular stents. Throughout her graduate study, she received multiple prestigious awards such as Pre-doctoral Clinical Research Training (TL1) scholarship from National Center for Advancing Translational Science at NIH, Society for Biomaterials (SFB) travel award, Dean of Engineering Scholarship and Graduate School Fund for Excellence and Innovation (GSFEI, UW). She is currently a T32 postdoctoral research fellow in the laboratories of Prof. Zhenan Bao and Prof. Sam Gambhir at Stanford University. Her interdisciplinary research lies at the interface of engineering and translational medicine and focuses on the development of wireless, implantable or wearable bioelectronics for early disease diagnosis and therapy.
Honors & Awards
Cancer-Translational Nanotechnology Training (Cancer-TNT) Program, Stanford (2019- 2021)
Honorable mention for an outstanding contribution to the Society For Biomaterials, Society For Biomaterials (2018)
National Institute of Health (NIH) fellowship, BloodSurf workshop (2017)
Graduate School Fund for Excellence and Innovation (GSFEI) Travel Award, University of Washington (2016&2018)
NIH (TL1) fellowship, Institute of Translational Health Sciences (ITHS) (2016)
World Biomaterial Congress (WBC) Travel Award, Society for Biomaterials (2016)
Commentary about “Biomaterials” selected as Next Generation Voices, Science magazine (2014)
Dean of Engineering scholarship, University of Texas at Arlington (2008-2010)
Doctor of Philosophy, University of Washington (2018)
BD Ratner, R Khalifehzadeh, E Naeemi, CU Lee, AJ Boydston. "United States Patent 10,577,456 Halogenated cyclic diesters, related polymers, and methods for their preparation and use", Mar 3, 2020
The CpG molecular structure controls the mineralization of calcium phosphate nanoparticles and their immunostimulation efficacy as vaccine adjuvants.
The co-precipitation of calcium phosphate nanoparticles (CaPs) in the presence of nucleotide chains such as polynucleotides (i.e., plasmid DNA and siRNA) and oligonucleotides has been extensively used for pre-clinical gene or drug delivery and immunotherapy studies. However, the exact role of these molecules in mineralization and tuning the physicochemical characteristics of the synthesized CaPs is still not entirely clear. In this study, we evaluated the effects of three different CpG oligodeoxynucleotides (ODN) and two representative nucleic acids (siRNA and DNA), when used as templates for the formation of CaPs. We examined the influence of CpGs with naturally-occurring phosphodiester or modified phosphorothioate backbones on the homogeneous formation of CaPs from a modified simulated body fluid solution. The hydrodynamic size, size polydispersity, morphology and surface charge of the CaPs were used as the most critical checkpoints to unravel the involved mechanisms. Our results show that the characteristics of CaPs are highly dependent on the composition, backbone, sequence and concentrations of the CpGs. The CpG type and concentration control the size distribution of the mineralized CaPs and their immunostimulation performance as verified by the activation of dendritic cells and secretion of the pro-inflammatory interleukin-6 (IL-6) cytokine, type I interferon-alpha (IFN-alpha) and co-stimulatory CD80, CD86 and CD40 markers. This study paves the way for better design of more efficient CaPs loaded with different types of CpGs for immunostimulation applications as vaccine adjuvants.
View details for DOI 10.1039/c9nr09782a
View details for PubMedID 32314980
Biodegradable calcium phosphate nanoparticles for cancer therapy.
Advances in colloid and interface science
2020; 279: 102157
Calcium phosphate is the inorganic mineral of hard tissues such as bone and teeth. Due to their similarities to the natural bone, calcium phosphates are highly biocompatible and biodegradable materials that have found numerous applications in dental and orthopedic implants and bone tissue engineering. In the form of nanoparticles, calcium phosphate nanoparticles (CaP's) can also be used as effective delivery vehicles to transfer therapeutic agents such as nucleic acids, drugs, proteins and enzymes into tumor cells. In addition, facile preparation and functionalization of CaP's, together with their inherent properties such as pH-dependent solubility provide advantages in delivery and release of these bioactive agents using CaP's as nanocarriers. In this review, the challenges and achievements in the intracellular delivery of these agents to tumor cells are discussed. Also, the most important issues in the design and potential applications of CaP-based biominerals are addressed with more focus on their biodegradability in tumor microenvironment.
View details for DOI 10.1016/j.cis.2020.102157
View details for PubMedID 32330734
Trifluoromethyl-functionalized poly(lactic acid): a fluoropolyester designed for blood contact applications
2019; 7 (9): 3764–78
Fluorinated polymers are strong candidates for development of new cardiovascular medical devices, due to their lower thrombogenicity as compared to other polymers used for cardiovascular implants. Few studies have reported the development of fluorinated polyesters and their potential in blood contact applications has never been examined. In this study, we developed a versatile method for preparing trifluoromethyl-functionalized poly(lactic acid) that can be potentially extended to prepare a new class of polyesters with various halogen or halocarbon substitutions. The resulting fluorinated polymer was hydrophobic relative to poly(lactic acid) and extracts from this polymer showed no in vitro cytotoxicity to NIH-3T3 mouse fibroblast cells. A preliminary consideration of the blood interactions of the CF3-functionalized polyester was evaluated by measuring the amount of the adsorbed albumin and fibrinogen from human blood plasma. The fluorinated polyester adsorbed and retained higher amounts of albumin and fibrinogen with a higher albumin/fibrinogen ratio as compared to poly(lactic acid), suggesting enhanced hemocompatibility. Plasma protein adsorption is the first event that occurs seconds after device implantation and controlling the adsorbed proteins will dictate the performance of medical implants.
View details for DOI 10.1039/c9bm00353c
View details for Web of Science ID 000482087100019
View details for PubMedID 31342016
- DNA-Templated Strontium-Doped Calcium Phosphate Nanoparticles for Gene Delivery in Bone Cells ACS BIOMATERIALS SCIENCE & ENGINEERING 2019; 5 (7): 3201–11
Surface fluorination of polylactide as a path to improve platelet associated hemocompatibility
2018; 78: 23–35
Surface-induced thrombosis is still a significant clinical concern for many types of blood-contacting medical devices. In particular, protein adsorption and platelet adhesion are important events due to their ability to trigger the coagulation cascade and initiate thrombosis. Poly(lactic acid) (PLA) has been the predominant polymer used for making bioresorbable stents. Despite long-term advantages, these stents are associated with higher rates of early thrombosis compared with permanent metallic stents. To address this issue, we modified the surface of PLA with a perfluoro compound facilitated by surface activation using radio frequency (RF) plasma. Fluoropolymers have been extensively used in blood contacting materials, such as blood vessel replacements due to their reduced thrombogenicity and reduced platelet reactivity. The compositions of plasma-treated surfaces were determined by electron spectroscopy for chemical analysis (ESCA). Also, contact angle measurements, cell cytotoxicity and the degradation profile of the treated polymers are presented. Finally, relevant blood compatibility parameters, including plasma protein adsorption, platelet adhesion and morphology, were evaluated. We hypothesized that tight binding of adsorbed albumin by fluoropolymers enhances its potential for blood-contacting applications.Although bioresorbable stents made from poly(lactic acid) (PLA) may have long-term clinical advantages, they have shown higher rates of early thrombosis as compared with permanent metallic stents. To improve the thromboresistance of PLA, we developed a novel method for surface fluorination of this polymer with a perfluoro compound. Fluoropolymers (e.g., expanded polytetrafluoroethylene) have long been used in blood-contacting applications due to their satisfactory clinical performance. This is the first report of PLA surface fluorination which might be applied to the fabrication of a new generation of fluorinated PLA stents with improved platelet interaction, tunable degradability and drug release capabilities. Also, we describe a general strategy for improving the platelet interactions with biomaterials based on albumin retention.
View details for DOI 10.1016/j.actbio.2018.07.042
View details for Web of Science ID 000445990200003
View details for PubMedID 30036719
- Facile Synthesis of Fluorine-Substituted Polylactides and Their Amphiphilic Block Copolymers MACROMOLECULES 2018; 51 (4): 1280–89
- Rapid formation of hydroxyapatite nanostrips via microwave irradiation JOURNAL OF ALLOYS AND COMPOUNDS 2009; 469 (1-2): 391-394
- Self-assembled nanostructured ZnO hollow spheres with UVA luminescence ADVANCES IN APPLIED CERAMICS 2009; 108 (2): 73-77
- Effect of predeformation and heat treatment conditions in the SIMA process on microstructural and mechanical properties of A319 aluminum alloy JOURNAL OF ALLOYS AND COMPOUNDS 2009; 468 (1-2): 130-135
- Synthesis of γ-Alumina Nanopowders from Synthetic Bayer Liquor and its Application for Oil and Gas Industries JOURNAL OF NANOCOMPOSITE MATERIALS RESEARCH (JNMR) 2009 ; 1 (2): 71-76
- Surfactant free hydrothermal formation of Pb3O4 nanorods JOURNAL OF ALLOYS AND COMPOUNDS 2008; 466 (1-2): 323-325
- Bundles of self-assembled boehmite nanostrips from a surfactant free hydrothermal route JOURNAL OF ALLOYS AND COMPOUNDS 2008; 461 (1-2): 551-554
ELECTROCHEMICAL DEPOSITION OF FLOWER-LIKE NICKEL NANOSTRUCTURES ON WELL-DEFINED n-Si(111):H
INTERNATIONAL JOURNAL OF ENGINEERING
2008; 21 (2): 177–82
View details for Web of Science ID 000444859800009
- Microporosity control and thermal-fatigue resistance of A319 aluminum foundry alloy MATERIALS SCIENCE AND ENGINEERING A-STRUCTURAL MATERIALS PROPERTIES MICROSTRUCTURE AND PROCESSING 2008; 472 (1-2): 107-114
- Self-assembled dahlia-like cadmium hydrogen phosphate hydrate nanostructures as templates for cadmium hydroxyapatite hexagonal prisms JOURNAL OF CRYSTAL GROWTH 2007; 309 (1): 37-42
- Electron beam-induced "nanocalcination" of boehmite nanostrips to mesoporous alpha-alumina phase JOURNAL OF THE AMERICAN CERAMIC SOCIETY 2007; 90 (10): 3311-3313
- Prediction of the effect of vacuum sintering conditions on porosity and hardness of porous NiTi shape memory alloy using ANFIS COMPUTATIONAL MATERIALS SCIENCE 2007; 40 (3): 359-365
- Sonochemical preparation of TiO2 nanoparticles MATERIALS LETTERS 2007; 61 (23-24): 4559-4561
- Polypyrrole/multiwall carbon nanotube nanocomposites electropolymerized on copper substrate MATERIALS LETTERS 2007; 61 (22): 4412-4415
- Studies on synthesis of alumina nanopowder from synthetic Bayer liquor MATERIALS RESEARCH BULLETIN 2007; 42 (6): 1004-1009
- Alumina nanopowder production from synthetic Bayer liquor JOURNAL OF THE AMERICAN CERAMIC SOCIETY 2006; 89 (12): 3654-3657
- Powder metallurgical fabrication and characterization of nanostructured porous NiTi shape-memory alloy MATERIALS AND MANUFACTURING PROCESSES 2006; 21 (8): 727-735