Development of bacteriochlorophyll a-based near-infrared photosensitizers conjugated to gold nanoparticles for photodynamic therapy of cancer

Abstract

We report the synthesis and characterization of a new sulfur-containing derivative of bacteriochlorophyll a. The latter was isolated from biomass of the nonsulfur purple bacterium Rhodobacter capsulatus strain B10. The developed photosensitizer is N-aminobacteriopurpurinimide with an exocyclic amino group acylated with a lipoic acid moiety, which is a biogenic substance that acts as a cofactor of the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes in the body. The disulfide moiety of lipoic acid confers the compound aurophilicity, thus allowing its conjugation with gold nanoparticles (NP-Au) via S-Au bonds. The shape and the size of the resulting nanoconjugate with immobilized photosensitizer (PS-Au) were assessed by dynamic light scattering and transmission electron microscopy. The conjugated nanoparticles are spherical with hydrodynamic diameter of 100-110 nm. The PS-Au conjugate absorbs light at 824 nm and emits strong fluorescence at 830 nm, which allowed in vivo study of its dynamic biodistribution in rats bearing sarcoma M-1. Compared to the free photosensitizer, PS loaded on the gold nanoparticles (PS-Au) showed extended circulation time in the blood and enhanced tumor uptake due to nonspecific passive targeting when the drug accumulates in tumor sites through the leaky tumor neovasculature and does not return to the circulation.

New Targeted Gold Nanorods for the Treatment of Glioblastoma by Photodynamic Therapy

“…These AuNRs are also familiar as drug delivery vehicles in cancer diagnostics and therapy [33][34][35][36][37][38][39][40][41][42][43]. The surface of the gold nanoparticles, in general, can be easily functionalized, thus establishing very stable conjugations [44]. This fact encouraged the linking of different PSs onto the surface of the AuNPs or NRs for a PDT or a combined PDT/PTT treatment, where they showed good efficiency [45][46][47][48].…”

Novel Photosensitizer Based on Bacteriopurpurinimide and Magnetite Nanoparticles

“…[7][8][9] On the other hand, PS immobilization onto the nanoparticles of different nature provides passive targeting, comprising the macromolecules extravasation from defective tumor vessels and their retention in the interstitium due to impaired lymphatic drainage tumor system (EPR-effect). [10][11][12][13] Nanostructures based on the bacteriochlorin PS and the magnetic iron oxide nanoparticles, proposed in this paper could be considered as perspective theranostic agent for photodynamic therapy and MRI diagnosis. Among various iron oxides nanoparticles the researchers focus most of their attention to the magnetite nanoparticles, due to their low toxicity, the possibility of functionalization by biomolecules and relative aggregative stability.…”

Electron-Transfer Secondary Reaction Matrices for MALDI MS Analysis ofBacteriochlorophyll ainRhodobacter sphaeroidesand Its Zinc and Copper Analogue Pigments

“…This distinctive feature explains their functioning in the dark and in places typically unreachable to other photosynthetic systems such as deep soil and sea, or internal organs of living species. For these reasons, BChl have a larger range of applications compared with Chl as they can be involved in bioremediation [5,6] or, very importantly, as elements of nanostructures in photodynamic therapy and nanomedicine [7,8]. Naturally occurring BChl and their derivatives represent an important group of photosensitizers (PS) since the strong absorption in the infra-red spectral region enables ablation of tumors that cannot be accessed by commonly employed PS such as chlorophylls, porphyrins, and phthalocyanines absorbing at shorter wavelengths.…”

“…Naturally occurring BChl and their derivatives represent an important group of photosensitizers (PS) since the strong absorption in the infra-red spectral region enables ablation of tumors that cannot be accessed by commonly employed PS such as chlorophylls, porphyrins, and phthalocyanines absorbing at shorter wavelengths. As a consequence, many synthetic strategies [7,9] or engineered biosynthesis [10] have been proposed to obtain novel derivatives of bacteriochlorophylls with improved photo-and chemical stability and enhanced photosensitizing properties. Thus, it becomes of paramount importance to develop a fast and simple method for characterizing the novel rationally designed BChl.…”