Nanoparticle (NP) bioconjugates have an important role in the development of photothermal (PT) therapy, a promising noninvasive approach wherein the NP acts as a light harvesting antenna to convert light into thermal energy to control cellular function. NP-mediated PT control of cellular membrane potential has gained significant interest in recent years as membrane potential regulates proliferation, migration, action potentials (in neurons), and contraction (in muscle cells). Recently gold nanoparticles (AuNPs) and Au nanorods have been demonstrated to induce action potentials via light-induced thermal activation of membrane tethered NPs. Spherical AuNPs have an efficient plasmonic output and are easily modified to interface with the cell surface. We demonstrate here that 20 nm diameter spherical AuNPs (tethered to the plasma membrane by a cholesterol moiety) transduce incident 532 nm light into proximal membrane heating that induces depolarization of membrane potential. Using these NP bioconjugates, we show the ability to controllably induce action potentials in dorsal root ganglion neurons and to control the membrane potential of rat pheochromocytoma cells. The ability to use light-actuated NP conjugates to control cellular behavior is an emerging research field with implications for neuronal and muscle cell modulation as well as in cancer therapeutics.
The main principle of photodynamic therapy (PDT) is to kill malignant cells by generation of reactive oxygen species (ROS). PDT appeared highly effective when ROS can be produced in subcellular location such as plasma membrane. The plasma membrane maintains the structural integrity of the cell and regulates multiple important cellular processes, such as endocytosis, trafficking, and apoptotic pathways, could be one of the best points to kill the cancer cells. Previously, we have developed a plasma membrane-targeted liquid crystal nanoparticle (LCNP) formulation that can be loaded with dyes or drugs. Here we highlight the utility of this LCNP for membrane targeted delivery and imaging for a photosensitizer (PS) for PDT applications.
In addition to maintaining the structural integrity of the cell, the plasma membrane regulates multiple important cellular processes, such as endocytosis and trafficking, apoptotic pathways and drug transport. The modulation or tracking of such cellular processes by means of controlled delivery of drugs or imaging agents <i>via</i> nanoscale delivery systems is very attractive. Nanoparticle-mediated delivery systems that mediate long-term residence (e.g., days) and controlled release of the cargoes in the plasma membrane while simultaneously not interfering with regular cellular physiology would be ideal for this purpose. Our laboratory has developed a plasma membrane-targeted liquid crystal nanoparticle (LCNP) formulation that can be loaded with dyes or drugs which can be slowly released from the particle over time. Here we highlight the utility of these nanopreparations for membrane delivery and imaging.
We report a two-photon (TP) absorbing molecular probe
1,4-bis(4'-(N,N-bis(6''-(N,N,N-trimethylammonium)hexyl)amino)-styryl)benzene tetrabromide (C1) and its
interaction with cells upon encapsulation with polymeric vesicles. Two-photon microscopy (TPM)
revealed that the free C1 specifically could bind to the plasma membrane and shows bright TP emission.
However, C1 encapsulated with polymeric vesicles internalized into the cytosol. In addition, fluorescence
quantum efficiency and TP cross section of encapsulated C1 enhanced by 2-fold. These results not only
show useful guidelines for the development of efficient TP probes, but also underscore the possibility of
using this type of nanostructure for intracellular delivery of the bioactive therapeutics.