Versatile Encapsulation and Synthesis of Potent Therapeutic Liposomes by Thermal Equilibration

The wide-scale use of liposomal delivery systems is hampered by difficulties in obtaining potent liposomal suspensions. Passive and active loading strategies have been proposed to formulate drug encapsulated liposomes, but are limited by low efficiencies (passive) or high drug specificities (active). Here, we present an efficient and universal loading strategy for synthesizing therapeutic liposomes. Integrating a thermal equilibration technique with our unique liposome synthesis approach, co-loaded targeting liposomes can be engineered in an efficient and scalable manner with potencies 200-fold higher than typical passive encapsulation techniques. We demonstrate this capability through simultaneous co-loading of hydrophilic and hydrophobic small molecules and through targeted delivery of liposomal Doxorubicin to a metastatic breast cancer cell line MDA-MB-231. Molecular dynamic simulations are used to explain interactions between Doxorubicin and liposome membrane during thermal equilibration. By addressing the existing challenges, we have developed an unparalleled approach that will facilitate the formulation of novel theranostic and pharmaceutical strategies.

Absent thermal equilibration on fractional quantum Hall edges over macroscopic scale

Two-dimensional topological insulators, and in particular quantum Hall states, are characterized by an insulating bulk and a conducting edge. Fractional states may host both downstream (dictated by the magnetic field) and upstream propagating edge modes, which leads to complex transport behavior. Here, we combine two measurement techniques, local noise thermometry and thermal conductance, to study thermal properties of states with counter-propagating edge modes. We find that, while charge equilibration between counter-propagating edge modes is very fast, the equilibration of heat is extremely inefficient, leading to an almost ballistic heat transport over macroscopic distances. Moreover, we observe an emergent quantization of the heat conductance associated with a strong interaction fixed point of the edge modes. This new understanding of the thermal equilibration on edges with counter-propagating modes is a natural route towards extracting the topological order of the exotic 5/2 state.

Thermal equilibration between singlet and triplet excited states in organic fluorophore for submicrosecond delayed fluorescence

In any complex molecular system, electronic excited states with different spin multiplicities can be described via a simple statistical thermodynamic formalism if the states are in thermal equilibrium. However, this ideal situation has hitherto been infeasible for efficient fluorescent organic molecules. Here, we report a highly emissive metal-free purely organic fluorophore that enables thermal equilibration between singlet and triplet excited states. The key to this unconventional excitonic behavior is the exceptionally fast spin-flipping reverse intersystem crossing from the triplet to singlet excited states with a rate constant exceeding 108 per second, which is considerably higher than that of radiative decay (fluorescence) from the singlet excited state. The present fluorophoric system exhibits an emission lifetime as short as 750 nanoseconds and, therefore, allows organic light-emitting diodes to demonstrate external electroluminescence quantum efficiency exceeding 20% even at a practical high luminance of more than 10,000 candelas per square meter.