Combinatory
modulation of the physical and biochemical characteristics
of nanocarrier delivery systems is an emergent topic in the field
of nanomedicine. Here, we studied the combined effects of incorporation
of active targeting moieties into nanocarriers and their morphology
affecting the enhanced permeation and retention effect for nanomedicine
cancer therapy. Self-assembled lipid discoidal and vesicular nanoparticles
with low-polydispersity sub-50 nm size range and identical chemical
compositions were synthesized, characterized, and correlated with
in vitro cancer cellular internalization, in vivo tumor accumulation
and cancer treatments. The fact that folate-associated bicelle yields
the best outcome is indicative of the preference for discoidal carriers
over spherical carriers and the improved targeting efficacy due to
the targeting ligand/receptor binding. The approach is successfully
adopted to design the nanocarriers for photodynamic therapy, which
yields a consistent trend in in vitro and in vivo efficacy: folate
nanodiscs > folate vesicles > nonfolate nanodiscs > nonfolate
vesicles.
Folate discs not only have shown a higher tumor uptake and photothermal
therapeutic efficiency, but also minimize skin photosensitivity side
effects. The advantages of nanodiscoidal bicelles as nanocarriers,
including well-defined size, robust formation, easy encapsulation
of hydrophobic molecules (therapeutics and/or diagnostics), easy incorporation
of targeting molecules, and low toxicity, enable the scalable manufacturing
of a generalized in vivo multimodal delivery platform.
Bicellar mixtures have been used as alignable membrane substrates for the structural characterization of membrane-associated proteins. Most recently, it has been shown that bicelles can serve as nanocarriers to effectively deliver hydrophobic molecules to cancer cells with a 3- to 10-fold enhancement compared to that of chemically identical liposomes. In this chapter, a detailed preparation protocol, common structural characterization methods, the structural stability and the cellular uptake of bicellar nanodisks are discussed.
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