Conceptual Nanomedical Lipofuscin Removal Strategy

(Y. Svidinenko and FJ Boehm – Apr/27/13)

Lipofuscin is a waxy heterogeneous substance that is comprised of aggregates of metabolic cellular waste end products, which reside within the lysosomes and cytosols of particular types of human cells. This substance can neither be degraded further via the typical complement of lysosomal enzymes, nor ejected from cells, but can be somewhat diluted through cell division and subsequent cellular growth. This autofluorescent pigment is considered to be a significant aging-associated "wear-and-tear" compound that is found in the liver, kidney, heart muscle, adrenals, nerve cells and ganglion cells. It is specifically arranged around the cell nucleus, and is a type of lipochrome.

In a broader context, lipofuscin is often considered as one of several forms of undesirable proteinaceous agglomerations; others sometimes called ceroids, inclusion bodies, plaques, or aggresomes, contingent on their source and composition. It accumulates over time within aging cells to become manifest as a significant percentage of a cell’s internal volume. As a consequence, it may impede normal cellular processes, affecting proteasomal activity and protein turnover, and is present as typical feature in neurodegenerative diseases as well as aging. Within the aging human brain, deposits of lipofuscin are not uniformly distributed, but rather, are concentrated at specific sites of functional interest. The prevailing thought is that the major source of lipofuscin is derived from the incomplete lysosomal degradation of cell membrane lipids and damaged mitochondria.

It is conceivable that the future development of nanomedical robotics, as described in the upcoming book: Nanomedical Device and Systems Design: Challenges, Possibilities, Visions (FJ Boehm – Editor), to be published on Nov/22/13 by CRC Press (Taylor & Francis) might enable the capacity for the therapeutic removal of lipofuscin from individual cells in massively parallel fashion. Conceptual dedicated autonomous nanodevices (~200 nm in diameter - where one nanometer is a billionth of a meter) might penetrate the cell membranes of neurons and other cells and undertake the removal of lipofuscin through various means, as described in the book excerpt below:

“Although entirely conceptual and seemingly impracticable currently (2013), advanced AI [Artificial Intelligence] involvement in the design/optimization of sophisticated nanomedical devices working in conjunction mature nanomanufacturing may indeed bring about much more complex, albeit far more rapid and efficient lipofuscin detection and removal. Advanced autonomous nanodevices might precisely locate lipofuscin granules by exploiting its strong fluorescence signatures (emission spectrum ranges from 450 to 700 nm)…. to match with onboard reference spectral profiles. The prospective armamentarium at the disposal of these autonomous diamondoid “defuscin” class nanodevices…. might allow for the complete eradication of lipofuscin aggregates utilizing a feedthrough digestive strategy. These entities may be propelled by arrays of oscillating piezoelectric “fins” or via integrated magnetic nanoparticles, which might be activated and controlled externally. The conical inlet port of the nanodevice would be lined with molecules that possess high affinities for A2E [a primary lipofuscin constituent] and other lipofuscin elements. Once a lipofuscin granule has been captured it would proceed to be drawn into the core, where it would be digested by potent encapsulated enzymes or nanomechanically minced into a liquid state and subsequently purged from the outlet port.”

“The desired result of this defuscin mediated digestion would be the fragmentation and ideally dissolution of the chemical crosslinks that provide lipofuscin its refractive properties. Other defuscin-class nanodevice designs may include proboscises that serve dual purposes; as potential electrodes for highly localized hyperthermic interventions, following insertion into the lipofuscin mass, or hollow nanosyringes… for the injection of powerful cleaving enzymes. The nanomechanical segmentation or disassembly of individual lipofuscin granules at atomic/molecular resolution may be possible employing arrays of diamondoid “debriders” to reduce lipofuscin to its most elemental and harmless fractions. Larger fragments could subsequently be encapsulated for egress through the urinary or gastrointestinal tracts.

The overarching premise here is that treated cells might be thus induced to a more robust state of health (perhaps functioning at more youthful levels) when this cellular burden is extricated.”