Associate Professor, Chemistry Department, Brooklyn College, The City University of New York
Ph.D. (Chemistry) University of Louisville, KY, USA
My research interests span across nanotechnology and nanomedicine with specific interest in designing and testing the theranostic nanoparticle systems, as well as bioconjugates for concurrent imaging and therapy of disease. We focus on formulating the nanoparticles for cancer therapy. The development of multifunctional nanoparticle-based platforms with targeting, drug loading, and imaging features offer better treatment/imaging efficiencies than free drugs or traditional imaging agents. This involves formulation of theranostic nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) or oil-in-water nanoemulsions. The nanoparticle-based formulations or bioconjugation offer lower toxicity profiles for many drug molecules, long in vivo circulation, and sustained release. We focus primarily on producing nanoparticle-based and peptide-based delivery methods for highly potent but also highly toxic chemotherapy agents e.g. platinum (II). We have synthesized new Pt (II) complexes with functional groups available for click chemistry, which gives an option to attach Pt (II) to other supports, such as biological carriers, polymers or oils. We have developed the Pt (II)-nuclear localization sequence peptide hybrid that shuttles Pt (II) directly into the nucleus. This led to dramatic improvements in Pt (II) delivery to the nucleus and higher cytotoxicity towards cancer cells. We have also prepared lipophilic nanoparticle formulations of Pt (II) stabilized with tripeptide KYF. The nanoemulsion showed superior biological activity when compared to free drug. The latter was an important proof-of-concept study demonstrating, for the first time, peptide stabilization of a nanostructure. Currently, we continue our research on peptide-stabilized nanoparticles exploring other materials, such as PLGA polymers as a nanoparticle’s core. We included combretastatin A4 (CA4), the tubulin-binding vascular disrupting agent, in the formulation. We found that the RGDFFF-coated nanoparticles combined with the CA4 were biologically active against angiogenic and cancer cells, and they effectively targeted tumors in vivo. Importantly, other targeting peptides could be easily included in the nanoparticle formulation, thus facilitating multi-receptor targeting approaches. In addition, we formulate nanoparticles with an array of small drug molecules that have different mechanisms of action, e.g. targeting mitochondria. This highlights our interest in pursuing the next generation nanoparticles, which are capable of targeted drug delivery to organelles in cancer cells.
Dragulska, SA, Wlodarczyk, MT, Poursharifi, M, Mieszawska, AJ, “Engineering of a tripeptide-stabilized nanoemulsion of oleic acid for biological imaging and drug delivery applications.” R JOVE 2019.
Dragulska, SA, Chen, Y, Wlodarczyk, MT, Poursharifi, M, Dottino, P, Ulijn, RV, Martignetti, JA, Mieszawska, AJ, “Tripeptide-stabilized oil-in-water nanoemulsions of an oleic acid-platinum (II) conjugate as an anticancer nanomedicine.” R Bioconjugate Chem. 2018, PMID 30001618.
Wlodarczyk, MT, Dragulska, SA, Camacho-Vanegas, O, Dottino, PR, Jarzecki, AA, Martignetti, JA, Mieszawska, AJ, “Platinum (II) complex – nuclear localization sequence peptide hybrid for overcoming platinum resistance in cancer therapy” R ACS Biomater. Sci. Eng. 2018, 4, 2, 463-467.
Duivenvoorden R, Tang J, Cormode DP, Mieszawska AJ, Izquierdo-Garcia D, Ozcan C, Otten MJ, Zaidi N, Lobatto ME, van Rijs SM, Priem B, Kuan EL, Martel C, Hewing B, Sager H, Nahrendorf M, Randolph GJ, Stroes ES, Fuster V, Fisher EA, Fayad ZA, Mulder WJ, “A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation” Nat. Commun. 2014, PMID 24445279.
Aneta J. Mieszawska et al. Patent pending 20A0022: Peptide-stabilized poly(lactic-co-glycolic) acid nanoparticles US Patent 9,555,049 B2 (01/31/2017).
Grants over the last 5 years
Mieszawska, AJ, PI