About

Stavroula Sofou is a professor in the Department of Chemical and Biomolecular Engineering at Johns Hopkins University. She is a member of the Cancer Invasion & Metastasis Program at the JHU Sidney Kimmel Comprehensive Cancer Center, holds a secondary appointment in the Department of Oncology, and is an associate researcher at the Institute of NanoBioTechnology (INBT). Sofou is recognized for her non-traditional approaches to combat difficult-to-kill cancers in diffusion-limited environments. Her research interests encompass fundamental studies of lipid bilayers and applications of biomaterials for drug delivery, focusing on harnessing intermolecular and interfacial interactions of self-assembling materials within biological settings. She combines this knowledge with engineering principles to design devices aimed at promoting human health. Her group investigates environmentally-responsive biomaterials tailored to perform specific tasks, with the goal of engineering devices and strategies to overcome challenging drug delivery limitations in cancer therapies. Two major applied research focuses are enabling uniform and prolonged distributions of therapeutics in solid tumors and designing new nanoparticle binding geometries for targeting receptors to effectively kill cells with low surface marker expression. Sofou’s work primarily involves the delivery of chemotherapeutics and radionuclides, including alpha-particle emitters. She has received numerous awards and grants, including the Research Scholar Grant from the American Cancer Society, and has been recognized with the 2023 Dionisopoulou Prize by the Academy of Athens. Sofou earned her PhD in Chemical Engineering at Columbia University, completed a post-doctoral fellowship in Medical Physics at Memorial Sloan-Kettering Cancer Center, and has held academic positions at NYU-Poly and Rutgers University.

Research topics

• Chemistry
• Nuclear medicine
• Pharmacology
• Cancer research
• Botany
• Biology
• Biophysics
• Internal medicine
• Biochemistry
• Medicine

Selected publications

• Systemic cocktails of actinium-225 radioconjugates for treatment of glioblastoma

  Journal of medical imaging and radiation sciences · 2026-03-01

  article1st authorCorresponding
  PublisherDOI

• Hypoxia restores the acidosis-induced inhibition of cancer cell dissemination

  Cell Reports · 2026-02-01 · 1 citations

  articleOpen access

  = 6.4) suppresses cell proliferation, metabolism, dissociation from tumor spheroids, and migration in vitro as well as extravasation in chick embryos and mice. Acidosis acutely inhibits motility by downregulating the activity of sodium-hydrogen exchanger isoform-1 (NHE1), which in turn suppresses phosphatidylinositol 3-kinase (PI3K)/Akt. PI3K/Akt inhibition blocks Yes-associated protein (YAP) translocation to the nucleus, reducing NHE1 and integrin-linked kinase (ILK) expression. The resulting reduction in NHE1-/ILK-dependent migration and ATP production is rescued by hypoxia across cell types. While certain cancer cells can adapt to long-term (>3 weeks) acidosis and acquire an aggressive phenotype, acidosis-induced adaptation is not universal and depends on the cell's ability to restrain reactive oxygen species overproduction via fatty acid oxidation.

  PublisherDOI

• A Digital Twin to Optimize Treatment Efficacy of Targeted Alpha-particle Therapies by Antibody-Radioconjugate Cocktails Against Solid Tumors

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-22 · 1 citations

  articleOpen accessSenior authorCorresponding

  Abstract Advanced solid tumors are incurable. Antibody-delivered targeted alpha-particle (α-particle) radionuclide therapies (TAT) comprise a tumor-agnostic treatment type, due to the unparalleled killing efficacy of, and irradiation precision (4-5 cell lengths) by, α-particles, as well as the selectivity in tumor cell targeting by antibody technologies. However, cells not being directly hit by α-particles will likely not be killed. METHODS To address the limited solid tumor penetration by highly specific and strongly binding antibody-radioconjugates, an experimentally informed digital twin, based on transport (diffusion/advection) first principles, was developed to describe an approach where a fraction of the administered (radio)activity is delivered by a separate type of a model α-particle antibody-radioconjugate of low(er)/no affinity for the same marker. The latter was chosen because it can irradiate cells residing in the deep regions of solid tumors away from vasculature. RESULTS The digital twin that was trained and validated on spheroids that were employed as surrogates of the avascular tumor regions, demonstrated that the investigated cocktails of antibody-radioconjugates with controlled affinities exhibited better inhibition of spheroid growth compared to the extent of growth inhibition by the high-affinity antibody-radioconjugate alone, for the same total (incubated) activity concentrations; this prediction was independent of spheroid size and/or level of expression of the targeted markers. CONCLUSION The findings of this study suggest that antibody-delivered TAT (that is already in the clinic) can be augmented by delivering a fraction of the same total activity by low(er) affinity antibody-radioconjugates. This combination of separate antibody-radioconjugates with variable affinities (for the same targeted marker) is a promising approach to possibly even more delay recurrence and further prolong survival of patients with advanced solid tumors.

  PublisherOA PDFDOI

• Low-dose temozolomide selectively increases glioblastoma’s vascular permeability, tumor microenvironment penetration and the killing potential of systemic actinium-225 α-particle dendrimer-radioconjugates improving treatment efficacy

  European Journal of Nuclear Medicine and Molecular Imaging · 2025-05-13 · 2 citations

  articleSenior author
  PublisherDOI

• Guiding treatment response by spatiotemporal control of α-particle deposition in solid tumors: the case for ‘affinity cocktails’ of antibody-radioconjugates

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-25

  articleOpen accessSenior authorCorresponding

  Abstract Antibody-radioconjugates are leading the investigational targeted alpha-particle (α-particle) therapies for the treatment of solid tumors that do not respond to approved therapies. Yet, there is still treatment failure in the clinic largely attributed to the heterogenous patterns of tumor irradiation by α-particles. Although α-particles are essentially impervious to resistance, attributed to the complex double-strand DNA breaks they cause while traversing cells, cells not being directly hit by α-particles will likely not be killed. The diffusion-limited poor tumor penetration of high-affinity (strongly-binding) antibody-radioconjugates combined with α-particles’ short-range in tissue (only 40-80μm), let tumor regions far from vasculature inadequately irradiated, therefore, possibly escaping treatment. METHODS To improve penetration of delivered activity within tumors, we engineered separate actinium-225 antibody-radioconjugates of variable affinities (‘affinity cocktails’) targeting the same marker on cancer cells, that were chosen based on their preferential irradiation of complementary regions of the same tumors. The cocktails comprise: (a) ‘high-affinity’ antibody-radioconjugates (as the ones on clinical trials), which mostly deliver their cargo in tumor cells close to the vasculature, where the ‘low(er)-affinity’ antibody-radioconjugates fail to deliver effective doses, due to their fast clearance; and (b) ‘low(er)-affinity’ antibody-radioconjugates, that penetrate the deeper parts of tumors farther from the vasculature, where the ‘high-affinity’ antibodies fail to reach. The efficacy of affinity cocktails was assessed in spheroids, that were employed as surrogates of tumor avascular regions, and on mice with subcutaneous xenografts of different cancer origin, expression levels and/or type of the targeted receptor: HER2 highly-expressing BT-474 breast cancer cells, HER2 moderately-expressing HEPG2 hepatoma cells, and/or HER1 low-expressing BxPC-3 pancreatic cancer cells. RESULTS Although the high-affinity antibody-radioconjugates were most lethal against cancer cells in monolayers, affinity cocktails were most effective in inhibiting spheroid growth, due to better collective spreading of the antibody-conjugates within the spheroids’ volume. On all mouse models, and for the same total injected activity, affinity cocktails resulted in the best tumor growth inhibition, even at lower tumor absorbed doses, compared to the high-affinity antibody-radioconjugates alone. CONCLUSIONS This proof-of-concept study in α-particle antibody-delivery to solid tumors demonstrates that ‘separating’ the two key processes of diffusion and reaction/binding improves treatment efficacy. This generalizable approach may augment antibody-radioconjugates already in clinical trials.

  PublisherOA PDFDOI

• Actinium-225 dendrimer-radioconjugates combined with low-dose standard-of-care chemotherapy: site-independent treatment of triple negative breast cancer metastases

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-27

  preprintOpen accessSenior authorCorresponding

  Abstract PURPOSE Metastatic triple negative breast cancer (mTNBC) is incurable largely due to the development of drug resistance, the lack of selective cell targeting, and/or limitations in tumor drug delivery that vary depending on the different (metastatic) tumor locations. METHODS The potential of a single type of systemic, targeted alpha-particle therapy (TAT) was investigated for addressing the above challenges of TNBC tumors implanted at different anatomic sites in mice. Actinium-225 dendrimer-radioconjugates alone, and/or after pretreatment with low-dose standard-of-care cisplatin, were assessed in vitro and on immune-competent 4T1-Balb/c mouse models with tumors implanted intracranially, orthotopically or subcutaneously. RESULTS In vitro , TAT’s efficacy was enhanced by cisplatin . In vivo , treatment was initiated well after tumors had grown (V to = 39 ± 14 mm 3 in the intracranial model, and V to =100mm 3 in the orthotopic and subcutaneous models). Across all tumor implantation sites, a unified correlation was observed between animal mean survival and the dendrimer-delivered tumor absorbed doses, which were selectively increased by low-dose cisplatin pretreatment . Importantly, in all animal models, the mean survival following systemic treatment with both modalities was significantly longer vs. each modality alone and/or vs. no treatment, at injected doses that did not cause long-term (10-month) toxicities in tumor-free mice. CONCLUSION Systemically-injected dendrimer-delivered TAT, combined with low-dose cisplatin pretreatment , can safely extend survival independent of mTNBC tumors’ anatomic site, potentially presenting a single type of therapy to simultaneously treat multi-site mTNBC.

  PublisherOA PDFDOI

• Preirradiation of Spheroids with ²²⁵Ac-Trastuzumab Improves Penetration of ²²⁵Ac-Liposomes and MIRDcell Predictions of Responses to Drug Cocktails

  Journal of Nuclear Medicine · 2025-06-12 · 2 citations

  articleOpen access

  This investigation examined the factors involved in predicting the responses of micrometastases to targeted ²²⁵Ac-based therapies and in optimizing these therapies through the use of cocktails of radiopharmaceuticals (RPTs). <b>Methods:</b> MIRDcell version 4 was used to model the surviving fraction (SF) of cells in multicellular spheroids that were treated with cocktails of ²²⁵Ac RPTs as previously reported by Howe et&nbsp;al. in this journal. Spheroids were treated with varying activity concentrations of [²²⁵Ac]Ac-DOTA-SCN-trastuzumab (²²⁵Ac-trastuzumab) and ²²⁵Ac-DOTA–encapsulating liposomes (²²⁵Ac-liposomes). With the total activity concentration kept constant at 13.75 kBq/mL, 5 different activity distributions among the liposomes and antibodies were evaluated: 0%, 30%, 50%, 70%, and 100% of the total activity on each carrier. Penetration of the ²²⁵Ac-trastuzumab and ²²⁵Ac-liposomes into the spheroids was obtained with fluorescent surrogates in the previous work and remeasured here to determine whether preirradiating the spheroids with ²²⁵Ac-trastuzumab affected the spatiotemporal distribution of the liposomes. These data were used to compare MIRDcell-predicted SFs with experimental spheroid outgrowths. In addition, the artificial intelligence tool in MIRDcell was used to optimize the best cocktail formulation of ²²⁵Ac-antibodies and ²²⁵Ac-liposomes to achieve SFs of less than 0.0001 while minimizing the number of total decays necessary. <b>Results:</b> The penetration profiles of spheroids with 200-µm radii show a 42% increase in the total number of decays attributed to ²²⁵Ac-liposomes between 0 and 100 µm from the centers of spheroids when first pretreated with 6.5 kBq/mL ²²⁵Ac-trastuzumab. The MIRDcell predictions based on liposome penetration data obtained after preirradiation with ²²⁵Ac-trastuzumab also provided a better match to the experimental data. Artificial intelligence optimization found that although ²²⁵Ac-liposomes alone are able to sterilize all the cancer cells in the spheroid, 44% more total decays are required than when using a cocktail of ²²⁵Ac-trastuzumab and ²²⁵Ac-liposomes. <b>Conclusion:</b> Penetration of ²²⁵Ac-liposomes was enhanced by pretreatment with ²²⁵Ac-trastuzumab, and strategies to optimize penetration into micrometastases are important for RPT therapy with carrier cocktails. RPT cocktails, as opposed to single agents, may be required to eliminate circulating tumor cells, disseminated tumor cells, and micrometastases.

  PublisherOA PDFDOI

• Combined, yet separate: cocktails of carriers (not drugs) for actinium-225 α-particle therapy of solid tumors expressing moderate-to-low levels of targetable markers

  European Journal of Nuclear Medicine and Molecular Imaging · 2024-04-19 · 7 citations

  articleSenior authorCorresponding
  PublisherDOI

• Transport Cocktails for Cancer Therapeutics

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-01-25 · 2 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Beyond biological cell heterogeneity, evidenced by different resistances to therapeutics, “delivery heterogeneity” crucially limits treatment efficacy for advanced solid tumors: variations in therapeutic drug delivery to different tumor areas (perivascular, perinecrotic) leading to nonuniform drug concentrations/doses and to unsuccessful treatment (cancer cell kill). Short-range (40-80 µm), high energy (1-5 MeV) alpha-particles successfully address the biological heterogeneity: the double-strand DNA breaks they cause make them impervious to cell resistance mechanisms. Multiresponsive nanocarriers and/or engineered antibody-drug-conjugates are elegant approaches to delivering such alpha-particle emitters. Delivery heterogeneity, however, remains a challenge in established (i.e. large, vascularized) tumors. Remarkably, delivery properties enabling efficacy at the cell scale (targeting selectivity, affinity, cell drug uptake) may act against spatial delivery uniformity at the tumor scale (binding-site barrier effect 1 ). We have previously demonstrated, in different mouse models, that spatial delivery uniformity, key to the effective killing of solid tumors, can be achieved utilizing combinations of different, distinct delivery carriers of the same emitter, but with different, complementary delivery properties, “leaving no cancer cell behind”. We build first principles reaction-transport models (quantitatively informed by experiments) that explain the “geographically complementary” behaviors of such carrier cocktails, and help optimally design these cocktails and their delivery protocols.

  PublisherOA PDFDOI

• Liposomes for drug delivery to cancer cells

  Elsevier eBooks · 2024-01-01

  book-chapter1st authorCorresponding
  PublisherDOI

Recent grants

• UNS: Collaborative Research: Unique binding geometries: Engineering & Modeling of Sticky Patches on Lipid Nanoparticles for Effective Targeting of Otherwise Untargetable cells

  NSF · $344k · 2015–2019

• Collaborative Research: Design of Multifunctional Doubly-Fusogenic Liposomes to Deliver Therapeutics and Diagnostics

  NSF · $390k · 2012–2016

Frequent coauthors

• Amey Bandekar

  38 shared

• Michelle Sempkowski

  26 shared

• Charles Zhu

  24 shared

• Frank Bruchertseifer

  Joint Research Centre

  21 shared

• Aliyah Morgenstern

  20 shared

• Martin G. Pomper

  The University of Texas Southwestern Medical Center

  17 shared

• Omkar Bhatavdekar

  Johns Hopkins University

  17 shared

• Sangeeta Ray Banerjee

  Johns Hopkins University

  17 shared

Labs

• Sofou GroupPI

Awards & honors

• Research Scholar Grant of the American Cancer Society
• Coulter Foundation awards
• Susan G. Komen awards
• NYSTAR funding
• NATO Science Fellow