Advances in Functionalized Photosensitive Polymeric Nanocarriers

Abstract

The synthesis of light-responsive nanocarriers (LRNs) with a variety of surface functional groups and/or ligands has been intensively explored for space-temporal controlled cargo release. LRNs have been designed on demand for photodynamic-, photothermal-, chemo-, and radiotherapy, protected delivery of bioactive molecules, such as smart drug delivery systems and for theranostic duties. LRNs trigger the release of cargo by a light stimulus. The idea of modifying LRNs with different moieties and ligands search for site-specific cargo delivery imparting stealth effects and/or eliciting specific cellular interactions to improve the nanosystems' safety and efficacy. This work reviews photoresponsive polymeric nanocarriers and photo-stimulation mechanisms, surface chemistry to link ligands and characterization of the resultant nanosystems. It summarizes the interesting biomedical applications of functionalized photo-controlled nanocarriers, highlighting the current challenges and opportunities of such high-performance photo-triggered delivery systems.

Keywords: functional nanoparticle; light-responsive drug delivery; photoresponsive nanoparticle; polymer nanocarrier.

Figure 1

Schematic illustration of photosensitive polymeric nanocarriers: photosensitive mechanism, functional nanocarriers, nanocarriers targeting, and drug release.

Figure 2

Photoresponsive molecules for phototriggered drug release.

Figure 3

Structures and characteristics of some cross-linkers.

Figure 4

Illustration of PNc synthesis, nanocarrier self-assembly, cargo co-encapsulation, and further functionalization with the CTB. Selective uptake of the resultant nanobioconjugate and UV-light induced cargo release into cardiomyocytes by an isomerization process of the azobenzene photosensitive molecule-containing pothosensitive nanocarrier. Reprinted with permission from [99]. Copyright 2020 Springer Nature.

Figure 5

Schematic of light-activated and targeted cytosolic delivery of membrane-impermeable compounds. (a) Antibody-functionalized NPs are loaded with fluorescent Alexa546 model dye and targeted to cells expressing P-gp-green fluorescent protein (GFP bound to the P-glycoprotein transporter). After NPs endocytosis (b), the cargo was released in the endosome (c). Exposure to light at the dye’s excitation wavelength (546 nm) promoted ROS-mediated membrane damage (d) with cytosolic delivery of Alexa546 exclusively in the P-gp expressing cells. Reprinted with permission from [87]. Copyright 2010 American Chemical Society.

Figure 6

(a) Schematic illustration showing the structure of pDA-PEG-Erbitux bioconjugate, where the anti-EGFR antibody (Erbitux) selectively targets EGFR on the cell membrane of an MDA-MB-468 cell. White-light (b) and NIR-II (c) fluorescence images of EGFR-positive MDA-MB-468 cells incubated with the pDA-PEG-Erbitux bioconjugate, showing positive staining of cells. White-light (d) and NIR-II (e) fluorescence images of EGFR-negative U87-MG cells incubated with the pDA-PEG-Erbitux bioconjugate, without evident staining of the cells. The scale bar is 40 μm. (f) Average NIR-II fluorescence of EGFR-positive MDA-MB-468 cells and negative U87-MG cells, showing a positive/negative ratio of ~5.8. The error bars in f are the s.d. of average fluorescence intensity from 20 cells in each NIR-II fluorescence image. Reprinted with permission from [173]. Copyright 2014 Springer Nature.

Figure 7

(a) The chemical structure of PPV-ST conjugated polymer and its structural change under visible light (λ = 550 nm) irradiation; (b) Schematic representation of the formation of drug-loaded PPV-ST-NP nanoparticles and structural change upon irradiation with visible light (λ = 550 nm) leading to the drug release in cells. Reprinted with permission from [184]. Copyright 2018 John Wiley and Son.