WIREs Nanomed Nanobiotechnol
Smart polymersomes for therapy and diagnosis: fast progress toward multifunctional biomimetic nanomedicines
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Challenges of polymersomes development for theranostic applications. Size of the branches is proportional to the number of articles dealing with the subject in a logarithmic scale.
(a) In vitro detection of Tat‐NIR polymersome‐loaded murine dendritic cells (NIR‐DCs). Differential interference contrast and fluorescent confocal microscopy images of a Tat‐NIR polymersome‐labeled murine dendritic cell (bar = 5 µm). Color indicates local fluorescence intensity (blue < red < yellow). (b) Representative image of a 96‐well plate with 100 µL of labeled NIR‐DCs in serial dilution. Top well contains 3000 NIR‐DCs and subsequent wells are 4× dilutions (bar = 5 mm). (c) Quantified fluorescence intensity values versus number of NIR‐DCs per well. (d) In vivo longitudinal tracking of NIR‐dendritic cells (NIR‐DCs) migration to the popliteal lymph node in a mice model. Representative intensity maps (top row) and corresponding lifetime‐gated intensity maps (bottom row) for a single mouse are presented for days 4, 6, 11, and 33 after a single subcutaneous injection of 105 NIR‐DCs into the right footpad. (Reprinted with permission from Ref 99. Copyright 2012 Springer)
Schematic representation of the preparation of the immunosensor (a). Amperometric response of the immunosensor (b) for detecting of different concentration of prostate specific antigen (PSA): (a) 10, (b) 5, (c) 1, (d) 0.5, and (e) 0.1 ng/mL. Measure at −0.4 V versus Ag/AgCl toward addition of 1 mM H2O2 in N2‐saturated PBS. (Reprinted with permission from Ref 70. Copyright 2012 Elsevier)
Design of lactoferrin‐conjugated biodegradable polymersome for glioma targeting (a). Polymersomes are simultaneously loaded with doxorubicin (Dox) as a model antitumor drug and tetrandrine (Tet) as an multi drug resistance (MDR) inhibitor. Lactoferrin (Lf) was conjugated on the surface of polymersomes, as glioma targeting ligand and to help overcome the obstruction of the BBB. Accumulation of targeted polymersomes in glioma (EPR effect and overcoming BBB) was evidenced by fluorescence imaging (b). The specific interaction of Lf‐conjugated polymersomes with glioma cells enhanced drug delivery into these cells, improving the chemotherapy of glioma as showed by the improved survival in rats (c). (Reprinted with permission from Ref 63. Copyright 2012 American Chemical Society)
Scheme summarizing the different routes employed to obtain targeted polymersomes, emphasizing the number of steps involved in each route—putting aside polymer synthesis. (a) Ligand binding to preformed polymersomes. (b) Functionalization of the polymer in bulk and subsequent polymersomes formation. Targeted polymersomes obtained from functional hydrophilic block containing copolymers. (c) Functional hydrophilic block obtained from chemical modification of the polymer precursor. (d) Amphiphilic copolymer containing a functional hydrophilic block obtained directly from polymer synthesis.29,54,55–57,61–66,68–74,76–78
Schematic representation of a reduction sensitive polymersome delivery system. Under reduction conditions, the diblock, which is formed by disulfide bond, disassembles leading to polymersome destabilization and subsequent drug release.
Various triggers can be used to control the drug release from polymersome delivery systems.
When injected in the body, a particulate drug delivery system faces a wide range of barriers. In circulation, the carrier may be promptly cleared by blood cells, liver, and spleen (clearance by phagocytic uptake or by filtration) or by the kidneys (through excretion) before it has the opportunity to access the target tissue. As a consequence, the delivery system has to display colloidal stability in physiological ionic strength and in contact with existent endogenous anionic molecules (i.e., glycosaminoglycans, opsonins, serum albumin, and other extra‐cellular proteins). Then, it has to interact with the cell surface to be internalized (B). Normally, endocytosed material is trafficked in the early endosome compartment (C), which can be recycled to the cell surface and excreted (D), or fuse with lysosomes, leading to degradation (E) or endosomal escape can occur (F), enabling the action of the loaded drug inside the cell.