Mannose‐Functionalized Hyperbranched Polyglycerol Loaded with Zinc Porphyrin: Investigation of the Multivalency Effect in Antibacterial Photodynamic Therapy

Abstract

The antibacterial photodynamic activity of hyperbranched polyglycerol (hPG) loaded with zinc porphyrin photosensitizers and mannose units was investigated. hPG, with a M of 19.5 kDa, was functionalized with about 15 molecules of the photosensitizer {5,10,15-tris(3-hydroxyphenyl)-20-[4-(prop-2-yn-1-ylamino)tetrafluorophenyl]porphyrinato}-zinc(II) by using copper(I)-catalyzed 1,3-dipolar cycloaddition (CuAAC). These nanoparticle conjugates were functionalized systematically with increasing loadings of mannose in the range of approximately 20 to 110 groups. With higher mannose loadings (ca. 58-110 groups) the water-insoluble zinc porphyrin photosensitizer could thus be transferred into a water-soluble form. Targeting of the conjugates was proven in binding studies to the mannose-specific lectin concanavalin A (Con A) by using surface plasmon resonance (SPR). The antibacterial phototoxicity of the conjugates on Staphylococcus aureus (as a typical Gram-positive germ) was investigated in phosphate-buffered saline (PBS). It was shown that conjugates with approximately 70-110 mannose units exhibit significant antibacterial activity, whereas conjugates with approximately 20-60 units did not induce bacterial killing at all. These results give an insight into the multivalency effect in combination with photodynamic therapy (PDT). On addition of serum to the bacterial cultures, a quenching of this antibacterial phototoxicity was observed. In fluorescence studies with the conjugates in the presence of increasing bovine serum albumin (BSA) concentrations, protein-conjugate associations could be identified as a plausible cause for this quenching.

Mannose‐Functionalized Nanoscaffolds for Targeted Delivery in Biomedical Applications

“…The immune system is designed to defend the body against foreign invaders, such as cancer cells and pathogens, and protect against related diseases. Unlike chemotherapy and its direct killing effect, immunotherapy mainly leverages a therapeutic effect to recognize and selectively attack tumor cells or different pathogens by the activation of an immune response . Immunotherapy based on nanotechnology is currently believed to be a promising therapeutic strategy for various cancer treatments, thanks to the efficient targeted delivery and controlled release of immune activators…”

“…Staegemann et al. synthesized mannose‐functionalized hyperbranched polyglycerol (hPG)–zinc porphyrin conjugates and investigated their multivalent interaction with the plant lectin concanavalin (Con A) and S. aureus …”

“…[60] Staegemann et al synthesized mannose-functionalized hyperbranched polyglycerol (hPG)-zinc porphyrin conjugates and investigated their multivalenti nteraction with the plant lectin concanavalin (Con A) and S. aureus. [61] Figure 2. Schematic illustration of multivalent mannose-functionalized nanoparticles for targeted and controlled drug delivery.…”

“…Unlike chemotherapy and its direct killing effect, immunotherapy mainly leverages at herapeutic effect to recognize and selectively attack tumor cells or differentp athogens by the activation of an immune response. [61] Immunotherapy based on nanotechnology is currently believed to be ap romising therapeutic strategy for various cancert reatments, thanks to the efficient targeted delivery and controlled releaseo fi mmune activators. [62] MR plays ac rucial role in both the innate immune response and the adaptive immune response of host defensea fter MRmediated endocytosis by meanso fM R-richm acrophages, DCs, and endothelial cells.…”

Selective Photoinactivation of Methicillin‐Resistant Staphylococcus aureus by Highly Positively Charged RuII Complexes

“…ROS, mainly singlet oxygen ( 1 O 2 ), are highly reactive and can damage DNA, proteins, and lipids effectively . The multi‐target feature of ROS not only renders aPDT highly potent in killing even multidrug resistant bacteria, but also makes bacteria difficult to develop any resistance against these multiple attacks …”