Andrew Mackay, PhD

Our lab engineers innovative protein-polymer tools and drug carriers that respond to their environment. Cancer and ocular drug delivery are our primary focus; however, we also develop biomaterials that modulate cell signaling and trafficking. Protein-polymers are repetitive polypeptides that can be expressed in cells, fused to functional peptides, and tuned to respond to cues such as temperature, concentration, or nanoassembly. Composed from genetically-engineered biomaterials, their sequence and behavior can be precisely tailored at the genetic level. Drug delivery in the eye and cancer is often limited by access to and retention at the target site. In addition, many small molecules are dose-limited by toxicity at peripheral sites in the body. Our strategy is to repackage drugs and functional peptides into protein-polymers that control release and reduce toxicity. Successful carrier strategies are being formulated and evaluated for translation to the clinic. Using these biomaterials, our group has recently made significant breakthroughs by assembling ‘microdomains’ inside living cells. When decorated with functional proteins, these microdomains are helping us to precisely modulate cellular biology. To explore the potential for these new tools, we explore fundamental relationships between microdomain phase behavior and interactions with other proteins, membranes, organelles, and cells. Please explore our lab website to learn more about our work.

Dr. MacKay received his SB in chemical engineering and biology from the Massachusetts Institute of Technology in 1999. A Howard Hughes Medical Institute Predoctoral Fellow, he completed his PhD at the University of California at San Francisco and Berkeley in the joint graduate group in Bioengineering in 2005. As a Kirschstein National Research Service Award Postdoctoral Fellow, Dr. MacKay studied at Duke University in the Department of Biomedical Engineering. In 2008 Dr. MacKay joined the faculty at the University of Southern California. Dr. MacKay is a full member of the USC Norris Comprehensive Cancer Center. He has authored over 49 peer-reviewed publications. His work is and has been supported by the US Army, NIH/NIGMS, NIH/NIBIB, NIH/NEI, StopCancer, USC Ming Hsieh Institute, and the USC Whittier Foundation. His group explores biomolecular engineering and nanomedicine. At the USC School of Pharmacy, Dr. MacKay has deep expertise teaching drug delivery, nanoscience, and pharmacokinetics.

• Corrigendum to “Anti-CD99 scFv-ELP nanoworms for the treatment of acute myeloid leukemia” [Nanomed: Nanotechnol Biol Med 29C (2020) 102236] Nanomedicine. 2024 Nov; 62:102783. . View in PubMed
• Serum and Tear Autoantibodies from NOD and NOR Mice as Potential Diagnostic Indicators of Local and Systemic Inflammation in Sjögren’s Disease bioRxiv. 2024 Oct 29. . View in PubMed
• Enhanced T cell activation and cytotoxicity against AML via targeted anti-CD99 nanoparticle treatment Biomed Pharmacother. 2024 Oct; 179:117265. . View in PubMed
• FLT3/CD99 Bispecific Antibody-Based Nanoparticles for Acute Myeloid Leukemia Cancer Res Commun. 2024 Aug 01; 4(8):1946-1962. . View in PubMed
• Steric stabilization of bioactive nanoparticles using elastin-like polypeptides Adv Drug Deliv Rev. 2024 03; 206:115189. . View in PubMed
• Synergy between Laminin-Derived Elastin-like Polypeptides (LELPs) Optimizes Cell Spreading Biomacromolecules. 2024 07 08; 25(7):4001-4013. . View in PubMed
• Noncovalent Conjugation of OVA323 to ELP Micelles Increases Immune Response Biomacromolecules. 2024 02 12; 25(2):1027-1037. . View in PubMed
• aB-Crystallin Peptide Fused with Elastin-like Polypeptide: Intracellular Activity in Retinal Pigment Epithelial Cells Challenged with Oxidative Stress Antioxidants (Basel). 2023 Sep 30; 12(10). . View in PubMed
• Biomimetic SARS-CoV-2 Spike Protein Nanoparticles Biomacromolecules. 2023 05 08; 24(5):2030-2041. . View in PubMed
• Protein and polypeptide mediated delivery to the eye Adv Drug Deliv Rev. 2022 09; 188:114441. . View in PubMed
• Supra-lacrimal protein-based carriers for cyclosporine A reduce Th17-mediated autoimmunity in murine model of Sjögren’s syndrome Biomaterials. 2022 04; 283:121441. . View in PubMed
• Intracellular Dynamin Elastin-like Polypeptides Assemble into Rodlike, Spherical, and Reticular Dynasomes Biomacromolecules. 2022 01 10; 23(1):265-275. . View in PubMed
• Bet v 1-displaying elastin-like polypeptide nanoparticles induce a strong humoral and weak CD4+ T-cell response against Bet v 1 in a murine immunogenicity model Front Immunol. 2022; 13:1006776. . View in PubMed
• Hydra-Elastin-like Polypeptides Increase Rapamycin Potency When Targeting Cell Surface GRP78 Biomacromolecules. 2022 08 08; 23(8):3116-3129. . View in PubMed
• Single-Cell Quantification of the Transition Temperature of Intracellular Elastin-like Polypeptides ACS Biomater Sci Eng. 2021 02 08; 7(2):428-440. . View in PubMed
• Intralacrimal Sustained Delivery of Rapamycin Shows Therapeutic Effects without Systemic Toxicity in a Mouse Model of Autoimmune Dacryoadenitis Characteristic of Sjögren’s Syndrome Biomacromolecules. 2021 03 08; 22(3):1102-1114. . View in PubMed
• Biosynthesized Multivalent Lacritin Peptides Stimulate Exosome Production in Human Corneal Epithelium Int J Mol Sci. 2020 Aug 26; 21(17). . View in PubMed
• A Multivalent ICAM-1 Binding Nanoparticle which Inhibits ICAM-1 and LFA-1 Interaction Represents a New Tool for the Investigation of Autoimmune-Mediated Dry Eye Int J Mol Sci. 2020 Apr 15; 21(8). . View in PubMed
• Live long and active: Polypeptide-mediated assembly of antibody variable fragments Adv Drug Deliv Rev. 2020 12; 167:1-18. . View in PubMed
• Adaptable antibody Nanoworms designed for non-Hodgkin lymphoma Biomaterials. 2020 12; 262:120338. . View in PubMed
• Anti-CD99 scFv-ELP nanoworms for the treatment of acute myeloid leukemia Nanomedicine. 2020 10; 29:102236. . View in PubMed
• Evaluation of extracellular matrix mimetic laminin bioactive peptide and elastin-like polypeptide FASEB J. 2020 05; 34(5):6729-6740. . View in PubMed
• The humanin peptide mediates ELP nanoassembly and protects human retinal pigment epithelial cells from oxidative stress Nanomedicine. 2020 02; 24:102111. . View in PubMed
• Anti-FLT3 nanoparticles for acute myeloid leukemia: Preclinical pharmacology and pharmacokinetics J Control Release. 2020 08 10; 324:317-329. . View in PubMed
• Advanced drug delivery 2020 – Parts 1,2 and 3 Adv Drug Deliv Rev. 2020; 156:1-2. . View in PubMed
• SIAL: A simple image analysis library for wet-lab scientists J Open Source Softw. 2020; 5(56). . View in PubMed
• Caveolin elastin-like polypeptide fusions mediate temperature-dependent assembly of caveolar microdomains ACS Biomater Sci Eng. 2020 01 13; 6(1):198-204. . View in PubMed
• Human Granulocyte-Macrophage Colony-Stimulating Factor Fused to Elastin-Like Polypeptides Assembles Biologically-Active Nanoparticles Bioconjug Chem. 2020 05 20; 31(5):1551-1561. . View in PubMed
• Berunda Polypeptides Carrying Rapalogues Inhibit Tumor mTORC1 Better than Oral Everolimus Biomacromolecules. 2020 08 10; 21(8):3038-3046. . View in PubMed
• Nanotoxicology of an Elastin-like Polypeptide Rapamycin Formulation for Breast Cancer Biomacromolecules. 2020 03 09; 21(3):1091-1102. . View in PubMed
• Thermally-Responsive Loading and Release of Elastin-Like Polypeptides from Contact Lenses Pharmaceutics. 2019 May 07; 11(5). . View in PubMed
• Generation of a Monoclonal Antibody to Detect Elastin-like Polypeptides Biomacromolecules. 2019 08 12; 20(8):2942-2952. . View in PubMed
• Inhibition of Cathepsin S Reduces Lacrimal Gland Inflammation and Increases Tear Flow in a Mouse Model of Sjögren’s Syndrome Sci Rep. 2019 07 02; 9(1):9559. . View in PubMed
• Molecular Targeting of Immunosuppressants Using a Bifunctional Elastin-Like Polypeptide Bioconjug Chem. 2019 09 18; 30(9):2358-2372. . View in PubMed
• Berunda Polypeptides: Biheaded Rapamycin Carriers for Subcutaneous Treatment of Autoimmune Dry Eye Disease Mol Pharm. 2019 07 01; 16(7):3024-3039. . View in PubMed
• A new temperature-dependent strategy to modulate the epidermal growth factor receptor Biomaterials. 2018 11; 183:319-330. . View in PubMed
• NOD and NOR mice exhibit comparable development of lacrimal gland secretory dysfunction but NOD mice have more severe autoimmune dacryoadenitis Exp Eye Res. 2018 11; 176:243-251. . View in PubMed
• Tunable assembly of protein-microdomains in living vertebrate embryos Adv Biosyst. 2018 10; 2(10). . View in PubMed
• Intracellular Delivery of Rapamycin From FKBP Elastin-Like Polypeptides Is Consistent With Macropinocytosis Front Pharmacol. 2018; 9:1184. . View in PubMed
• Intra-vitreal aB crystallin fused to elastin-like polypeptide provides neuroprotection in a mouse model of age-related macular degeneration J Control Release. 2018 08 10; 283:94-104. . View in PubMed
• A novel elastin-like polypeptide drug carrier for cyclosporine A improves tear flow in a mouse model of Sjögren’s syndrome J Control Release. 2018 12 28; 292:183-195. . View in PubMed
• Elastin-like polypeptide switches: A design strategy to detect multimeric proteins Protein Sci. 2017 Sep; 26(9):1785-1795. . View in PubMed
• Berunda Polypeptides: Multi-Headed Fusion Proteins Promote Subcutaneous Administration of Rapamycin to Breast Cancer In Vivo Theranostics. 2017; 7(16):3856-3872. . View in PubMed
• Rapamycin Eye Drops Suppress Lacrimal Gland Inflammation In a Murine Model of Sjögren’s Syndrome Invest Ophthalmol Vis Sci. 2017 01 01; 58(1):372-385. . View in PubMed
• Bifunctional Elastin-like Polypeptide Nanoparticles Bind Rapamycin and Integrins and Suppress Tumor Growth in Vivo Bioconjug Chem. 2017 11 15; 28(11):2715-2728. . View in PubMed
• Elastin-like polypeptides: Therapeutic applications for an emerging class of nanomedicines J Control Release. 2016 10 28; 240:93-108. . View in PubMed
• Engineering structure and function using thermoresponsive biopolymers Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2016 Jan-Feb; 8(1):123-38. . View in PubMed
• Tear-mediated delivery of nanoparticles through transcytosis of the lacrimal gland J Control Release. 2015 Jun 28; 208:2-13. . View in PubMed
• A thermo-responsive protein treatment for dry eyes J Control Release. 2015 Feb 10; 199:156-67. . View in PubMed
• Image-driven pharmacokinetics: nanomedicine concentration across space and time Nanomedicine (Lond). 2015; 10(18):2861-79. . View in PubMed
• Lacritin-mediated regeneration of the corneal epithelia by protein polymer nanoparticles J Mater Chem B. 2014 Dec 14; 2(46):8131-8141. . View in PubMed
• Protein polymer nanoparticles engineered as chaperones protect against apoptosis in human retinal pigment epithelial cells J Control Release. 2014 Oct 10; 191:4-14. . View in PubMed
• An amphipathic alpha-helical peptide from apolipoprotein A1 stabilizes protein polymer vesicles J Control Release. 2014 Oct 10; 191:15-23. . View in PubMed
• Flipping the Switch on Clathrin-Mediated Endocytosis using Thermally Responsive Protein Microdomains Adv Funct Mater. 2014 Sep 10; 24(34):5340-5347. . View in PubMed
• Multimeric disintegrin protein polymer fusions that target tumor vasculature Biomacromolecules. 2014 Jul 14; 15(7):2347-58. . View in PubMed
• A hybrid protein-polymer nanoworm potentiates apoptosis better than a monoclonal antibody ACS Nano. 2014 Mar 25; 8(3):2064-76. . View in PubMed
• Triggered sorting and co-assembly of genetically engineered protein microdomains in the cytoplasm Adv Mater. 2014 Jan 22; 26(3):449-54. . View in PubMed
• Genetically engineered nanocarriers for drug delivery Int J Nanomedicine. 2014; 9:1617-26. . View in PubMed
• A quantitative recipe for engineering protein polymer nanoparticles Polym Chem. 2014 Jan; 5(5):1614-1625. . View in PubMed
• Elastin-based protein polymer nanoparticles carrying drug at both corona and core suppress tumor growth in vivo J Control Release. 2013 Nov 10; 171(3):330-8. . View in PubMed
• A rapamycin-binding protein polymer nanoparticle shows potent therapeutic activity in suppressing autoimmune dacryoadenitis in a mouse model of Sjögren’s syndrome J Control Release. 2013 Nov 10; 171(3):269-79. . View in PubMed
• Switchable elastin-like polypeptides that respond to chemical inducers of dimerization Biomacromolecules. 2013 Apr 08; 14(4):976-85. . View in PubMed
• Kinetic quantification of protein polymer nanoparticles using non-invasive imaging Integr Biol (Camb). 2013 Jan; 5(1):183-94. . View in PubMed
• A tunable and reversible platform for the intracellular formation of genetically engineered protein microdomains Biomacromolecules. 2012 Nov 12; 13(11):3439-44. . View in PubMed
• Elastin-like peptide amphiphiles form nanofibers with tunable length Biomacromolecules. 2012 Sep 10; 13(9):2645-54. . View in PubMed
• Biodegradation of elastin-like polypeptide nanoparticles Protein Sci. 2012 Jun; 21(6):743-50. . View in PubMed
• Design and cellular internalization of genetically engineered polypeptide nanoparticles displaying adenovirus knob domain J Control Release. 2011 Oct 30; 155(2):218-26. . View in PubMed
• Proceedings of the National Academy of Inventors Nanoscale Self-Assembly for Delivery of Therapeutics and Imaging Agents. 2011; 1(13):5-25. . View in PubMed
• NANOSCALE SELF-ASSEMBLY FOR DELIVERY OF THERAPEUTICS AND IMAGING AGENTS Technol Innov. 2011 Jan 01; 13(1):5-25. . View in PubMed
• Quantitative model of the phase behavior of recombinant pH-responsive elastin-like polypeptides Biomacromolecules. 2010 Nov 08; 11(11):2873-9. . View in PubMed
• Theranostic agents that co-deliver therapeutic and imaging agents? Adv Drug Deliv Rev. 2010 Aug 30; 62(11):1003-4.. View in PubMed
• Imaging and drug delivery using theranostic nanoparticles Adv Drug Deliv Rev. 2010 Aug 30; 62(11):1052-1063. . View in PubMed
• Injectable intratumoral depot of thermally responsive polypeptide-radionuclide conjugates delays tumor progression in a mouse model J Control Release. 2010 May 21; 144(1):2-9. . View in PubMed
• Biomolecular engineering of intracellular switches in eukaryotes J Drug Deliv Sci Technol. 2010 May; 20(3):163-169. . View in PubMed
• Recursive directional ligation by plasmid reconstruction allows rapid and seamless cloning of oligomeric genes Biomacromolecules. 2010 Apr 12; 11(4):944-52. . View in PubMed
• Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection Nat Mater. 2009 Dec; 8(12):993-9. . View in PubMed
• Environmentally responsive peptides as anticancer drug carriers Adv Drug Deliv Rev. 2009 Sep 30; 61(11):940-52. . View in PubMed
• In situ growth of a stoichiometric PEG-like conjugate at a protein’s N-terminus with significantly improved pharmacokinetics Proc Natl Acad Sci U S A. 2009 Sep 08; 106(36):15231-6. . View in PubMed
• Fabrication of elastin-like polypeptide nanoparticles for drug delivery by electrospraying Biomacromolecules. 2009 Jan 12; 10(1):19-24. . View in PubMed
• Temperature sensitive peptides: engineering hyperthermia-directed therapeutics Int J Hyperthermia. 2008 Sep; 24(6):483-95. . View in PubMed
• HIV TAT peptide modifies the distribution of DNA nanolipoparticles following convection-enhanced delivery Mol Ther. 2008 May; 16(5):893-900. . View in PubMed
• Improved non-chromatographic purification of a recombinant protein by cationic elastin-like polypeptides Biomacromolecules. 2007 May; 8(5):1417-24. . View in PubMed
• Stimulus responsive elastin biopolymers: Applications in medicine and biotechnology Curr Opin Chem Biol. 2006 Dec; 10(6):652-7. . View in PubMed
• Acid-triggered transformation of diortho ester phosphocholine liposome J Am Chem Soc. 2006 Jan 11; 128(1):60-1. . View in PubMed
• Designing dendrimers for biological applications Nat Biotechnol. 2005 Dec; 23(12):1517-26. . View in PubMed
• Thiocholesterol-based lipids for ordered assembly of bioresponsive gene carriers Mol Ther. 2005 Mar; 11(3):409-17. . View in PubMed
• Distribution in brain of liposomes after convection enhanced delivery; modulation by particle charge, particle diameter, and presence of steric coating Brain Res. 2005 Feb 28; 1035(2):139-53. . View in PubMed
• Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1 Cell. 2005 Feb 11; 120(3):343-55. . View in PubMed
• Low-pH-sensitive poly(ethylene glycol) (PEG)-stabilized plasmid nanolipoparticles: effects of PEG chain length, lipid composition and assembly conditions on gene delivery J Gene Med. 2005 Jan; 7(1):67-79. . View in PubMed
• Low-pH-sensitive PEG-stabilized plasmid-lipid nanoparticles: preparation and characterization Bioconjug Chem. 2003 Mar-Apr; 14(2):420-9. . View in PubMed
• Mechanism of pH-triggered collapse of phosphatidylethanolamine liposomes stabilized by an ortho ester polyethyleneglycol lipid Biophys J. 2003 Mar; 84(3):1784-95. . View in PubMed
• HIV TAT Protein Transduction Domain Mediated Cell Binding and Intracellular Delivery of Nanoparticles J Dispers Sci Technol. 2003; 24(3):465-473. . View in PubMed
• Selective differentiation of mammalian bone marrow stromal cells cultured on three-dimensional polymer foams J Biomed Mater Res. 2001 May; 55(2):229-35. . View in PubMed

• Hamm-Alvarez, Sarah