synthesis-characterization-multi-modal-phase-change-porphyrin

Synthesis and Characterization of Multi-Modal Phase-Change Porphyrin Droplets

Phase-change droplets are a class of ultrasound contrast agents that can convert into echogenic microbubbles in situ with the application of sufficient ...

Princess Margaret Cancer Centre

University of Toronto

The physical effects of small sugars on membranes have been studied for decades, primarily because of their membrane stabilization in cold or dehydrated environments. We studied the effects of up to 20 mol% glucose in bilayers made of 1,2-dimyristoyl--glycero-3-phosphocholine (DMPC) at low hydration by combining X-ray diffraction and Molecular Dynamics (MD) simulations. In agreement with previous studies, we observe membrane thinning at low and membrane thickening at high sugar concentrations. Glucose was found to preferentially localize to the outer head region of phospholipid bilayers at all concentrations, and partitioning of sugar in the membranes was found to monotonically increase with increasing sugar concentration. While the number of gauche defects in the lipid acyl tails and the lipid packing in the presence of sugar resembled values of a fluid lipid bilayer, tail dynamics, as assessed by autocorrelation of the carbon atoms in the phospholipid tails, were slowed down significantly with increasing glucose content. Thus, our findings suggest that sugar leads to a a disordered, glassy state of the hydrophobic membrane core. The non-monotonic effect of glucose on membrane thickness was found to be an effect of fluidification at low concentrations and decreased interdigitation in the higher sugar concentration regime.

Glucose Can Protect Membranes against Dehydration Damage by Inducing a Glassy Membrane State at Low Hydrations.

The enhanced permeability and retention (EPR) effect has underlain the predominant nanomedicine design philosophy for the past three decades. However, growing evidence suggests that it is over-represented in preclinical models, and agents designed solely using its principle of passive accumulation can only be applied to a narrow subset of clinical tumors. For this reason, strategies that can improve upon the EPR effect to facilitate nanomedicine delivery to otherwise non-responsive tumors are required for broad clinical translation. EPR-adaptive nanomedicine delivery comprises a class of chemical and physical techniques that modify tumor accessibility in an effort to increase agent delivery and therapeutic effect. In the present review, we overview the primary benefits and limitations of radiation, ultrasound, hyperthermia, and photodynamic therapy as physical strategies for EPR-adaptive delivery to EPR-insensitive tumor phenotypes, and we reflect upon changes in the preclinical research pathway that should be implemented in order to optimally validate and develop these delivery strategies.

Alexander Dhaliwal

Princess Margaret Cancer Centre

Synthesis and Characterization of Multi-Modal Phase-Change Porphyrin Droplets