Design and Development of Theranostic Nanomedicines - Nanotechnology for Biomedical Imaging and Diagnostics - page 431

monitoring of drug accumulation and even therapeutic response due to their bio-
compatibility, chemical functionality, and potential to combine drug delivery and
hyperthermia [85]. The promising subclasses are thermosensitive Mls with tumor-
targeting ligand, which release the drug payload by reaching critical temperature.
hyperthermia, achieved by alternating magnetic field, will trigger drug release and,
synergistically with the drug, kill tumor cells [86]. Mls are a prime example of
multipurposing a single theranostic formulation component for more than one role,
which then simplifies the overall formulation while increasing its functionality. in a
recent study, very small hydrophobic spions, 5 nm maghemite (Fe 2 o 3 ) capped with
oleic acid (oa), were embedded within lipid bilayers of a liposome [87]. particles in
the magnetic field generate heat that triggers the drug release. The same particles
also provide contrast for Mri.
liposomes proved to be highly versatile drug delivery systems and were used to
improve drug efficacy, bioavailability, targeting, and toxicity profile [88]. They
found broad application in tumor therapy, immunology, dermatology, treatment of
the eye disorders, brain targeting, and treating infection and as vaccine adjuvant for-
mulations. Furthermore, liposomes were explored for delivery of poorly soluble
small-molecule drugs to large macromolecules and biologics such as plasmid Dna,
sirna, and protein drugs. Therefore, liposomes as theranostic formulations provide
a wide range of opportunities for personalized nanomedicine. For example, in a
recent study, multimodal imaging liposome with targeted delivery and controlled
release features was developed [84]. The liposomes were composed of DspC/
cholesterol/gd-DoTa-Dspe/DoTa-Dspe with the molar ratio of 39:35:25:1
and ammonium sulfate/ph gradient. The presence of the gradient allowed them
to postload the anticancer drug (DoX), the gamma imaging radionuclide techne-
tium-99m ( 99m Tc) ( T 1/2 = 6.0 h, 141 kev γ-ray), and the therapeutic radionuclides
rhenium-186/rhenium-188 ( 186 re/ 188 re). in addition, nir lipid conjugate could also
be introduced post liposome formation. The resulting formulation became a highly
versatile theranostic platform where multiple imaging agents and therapeutic modal-
ities would be combined during and postprocessing [84]. Therapeutic anticancer
sirna delivery with magnetic liposome was also reported [89]. These examples
suggest that liposomes may represent the most versatile theranostic nanomedicine
platform with high likelihood of reaching clinical success.
liposomes have been investigated for targeted delivery since the late 1970s.
several liposomal formulations are currently approved for clinical use [90]. With the
development of long-circulating sTealTh liposomes, passive targeting to tissues
and organs was clinically achievable. The introduction of peg to liposomal surface
increased their steric stabilization in vivo and extended the circulation lifetime, which
further facilitated the passive targeting via epr effect [91]. passive and active targeting
was utilized in Tpgs-coated theranostic liposomes [92]. however, passive targeting
is typically combined with active targeting. active targeting of liposomal formula-
tions for drug delivery is well studied and extensively reviewed elsewhere. (in-depth
discussion is available in the following references [93-97].) Folate is the most
common cancer-targeting agent used for a large number of nanosystems and so
far the only one applied to theranostic liposomes [92]. We argue that more ligands