posted on 2018-01-26, 00:00authored byAnil Kumar Sahoo, Subbarao Kanchi, Taraknath Mandal, Chandan Dasgupta, Prabal K. Maiti
One
of the major challenges of nanomedicine and gene therapy is the effective
translocation of drugs and genes across cell membranes. In this study,
we describe a systematic procedure that could be useful for efficient
drug and gene delivery into the cell. Using fully atomistic molecular
dynamics (MD) simulations, we show that molecules of various shapes,
sizes, and chemistries can
be spontaneously encapsulated in a single-walled carbon nanotube (SWCNT)
embedded in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
(POPC) lipid bilayer, as we have exemplified with dendrimers, asiRNA,
ssDNA, and ubiquitin protein. We compute the free energy gain by the
molecules upon their entry inside the SWCNT channel to quantify the
stability of these molecules inside the channel as well as to understand
the spontaneity of the process. The free energy profiles suggest that
all molecules can enter the channel without facing any energy barrier
but experience a strong energy barrier (≫kBT) to translocate across the channel.
We propose a theoretical model for the estimation of encapsulation
and translocation times of the molecules. Whereas the model predicts
the encapsulation time to be of the order of few nanoseconds, which
match reasonably well with those obtained from the simulations, it
predicts the translocation time to be astronomically large for each
molecule considered in this study. This eliminates the possibility
of passive diffusion of the molecules through the CNT–nanopore
spanning across the membrane. To counter this, we put forward a mechanical
method of ejecting the encapsulated molecules by pushing them with
other free-floating SWCNTs of diameter smaller than the pore diameter.
The feasibility of the proposed method is also demonstrated by performing
MD simulations. The generic strategy described here should work for
other molecules as well and hence could be potentially useful for
drug- and gene-delivery applications.