SofouGroup
RESEARCH
TRANSPORT COCKTAILS for SOLID TUMOR THERAPY
to overcome the heterogeneous intratumoral drug microdistributions
The Sofou lab employs more than one, separate delivery carriers, of the same drug, chosen to deliver their therapeutic cargo in complementary regions of the same solid tumor. Collectively, the drug is well-spread within established, soft-tissue solid tumors. We have demonstrated remarkable improvements in cancer therapy including: (1) better tumor growth inhibition, (2) elimination of formation of spontaneous metastases, and/or (3) prolonged survival, in tumor bearing mice at low injected doses. This is a tumor agnostic strategy: we have demonstrated the applicability of this approach on a variety of solid tumors using a variety of (same drug) delivery carriers. It is not about the carrier, it is about where the drug goes!
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FUNDAMENTAL STUDIES ON LIPID BILAYERS
In bilayer membranes composed of lipid mixtures, the lateral distribution of lipids is not necessarily homogeneous. Actually it almost never is. Depending on intermolecular forces, it is possible to have lateral lipid reorganization resulting in a membrane that appears as a mosaic, as a surface patterned at the nanometer and micrometer scale.
We systematically alter the balance between electrostatic, hydrogen bonding, and van der Waals interactions among lipids forming heterogeneous lateral assemblies on giant unilamellar vesicles with the aim to understand the major factors driving lipid separation and to potentially design materials with environmentally responsive morphologies.
TARGETED CHEMOTHERAPY
We engineer liposomes that respond to different environments by forming heterogeneities resembling ‘lipid rafts’, with the aim to maximize tumor localization and targeting selectivity, and to accelerate drug release for superior tumor control at low toxicities.
Liposomes with ‘raft switches’ are designed from biophysical principles for pH-triggered binding activity (multivalency) and pH-triggered release of therapeutics.
TRANSPORT LIMITATIONS IN LIPOSOMAL CHEMOTHERAPY
We develop environmentally responsive lipid carriers that aim to increase penetration and homogeneity of chemotherapeutics in vascularized tumors.
ANTIVASCULAR ALPHA-PARTICLE THERAPY
Alpha particles are short range, high energy particles that efficiently kill cells but are very toxic. Neovasculature targeting lipid vesicles with encapsulated alpha-particle generators are designed to selectively target the tumor endothelium and efficiently deliver lethal doses while sparing the host from corresponding toxicities.
TRANSLATIONAL RESEARCH
Optimization of therapeutic outcomes in vivo. Emphasis on toxicity minimization and/or redistribution.