posted on 2021-11-09, 20:03authored byPriya Rajdev, Pradip Dey, Indranil Ghosh, Rajesh Khamrui, Joy Kar, Siddhartha Sankar Jana, Suhrit Ghosh
Cellular uptake is an important event
in drug delivery and other
biomedical applications. Amphiphilic polymers produce aggregates of
different size and shape depending on the intrinsic structural differences
and the packing parameter. Although they have been explored for various
biomedical applications with immense interest, the relationship between
the shape of the aggregate and cellular uptake has been studied only
in limited examples. This work reports two polymers (P1 and P2), both
of which contain a hydrophobic supramolecular structure-directing
unit (SSDU) at the chain-end of a fluorescence dye-labeled hydrophilic
polymer. Depending on the difference in the structure of the single
H-bonding functional group (hydrazide or amide) of the SSDU, P1 and
P2 produce polymersomes (NS1) and spherical micelles (NS2), respectively.
An aged solution of P2 produces cylindrical micelles (NS3). Confocal
microscopy studies reveal that the uptake of these nanostructures
in HeLa cells greatly depends on the shape of the aggregate. Spherical
NS1 and NS2 show appreciable uptake at 1 or 4 h of incubation, whereas
NS3 shows negligible uptake. Temperature-dependent cellular uptake
studies reveal an energy-dependent endocytosis pathway. Kinetic studies
show gradual increase in the cellular uptake with time, and at 24
h the relative uptake ratio (NS1:NS2:NS3) is 1.0:0.2:<0.1, implying
the polymersome morphology (NS1) is most efficient for cellular uptake
compared to the spherical or cylindrical micelles. The same trend
was also noticed for MDA-MB 231 cells. Confocal microscopy studies
further reveal cellular internalization and intracellular location
of NS1, which showed maximum cellular uptake. As the intrinsic difference
in the chemical structure of the two polymers is negligible, the observed
difference can be explicitly assigned to their difference in shape.