Bismuth Sulfide Nanorods with Retractable Zinc Protoporphyrin Molecules for Suppressing Innate Antioxidant Defense System and Strengthening Phototherapeutic Effects

Abstract

to our best knowledge, there is no report focusing on the photodynamic performance of Bi-based NMs yet. Theoretically, as a narrow bandgap semiconductor, [2a] Bi 2 S 3 can be excited by NIR laser to generate free electrons in the conduction band (CB) and holes in the valence band (VB), which can react with oxygen and water to form superoxide and hydroxyl radicals, respectively, for potential NIR-activated photodynamic therapy (PDT). However, in view of the fast electron-hole recombination, above reactive oxygen species (ROS) production is dramatically suppressed. Thus, development of sophisticated Bi 2 S 3based nanosystems to enable efficient electron-hole separation potentially can endow Bi 2 S 3 with the photodynamic performance, affording combination with photothermal therapy (PTT) and CT imaging. Besides the low ROS production efficiency, the innate antioxidant defense capability of tumor cells is usually another obstacle to effective PDT because the overexpressed phase II enzymes in tumor cells can provide sustainable protection against elevated ROS stress. [6] Heme oxygenase (HO-1), the most important phase II enzyme, has been known to be highly expressed in solid tumor, [6,7] playing a critical role in antioxidant defense. [8] Once cells are attacked by ROS, the redox homeostasis is disturbed and HO-1 can catalyze the heme molecule to generate a series of antioxidants (such as biliverdin, carbon monoxide, and ferrous iron), which are the most potent endogenous scavengers of ROS. It has been reported that zinc protoporphyrin IX (ZP) can work as a potent HO-1 inhibitor to suppress the HO-1 activity because ZP is a heme derivative and can more competitively bind to the active site of HO-1 enzyme than heme. [9] Thus, ZP potentially can be employed to inhibit HO-1 activity for strengthening PDT effect.The staggered energy band edges in heterogeneous materials can efficiently facilitate electron-hole separation. [10] The lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO) energies of ZP are −1.48 and 0.63 V versus standard hydrogen electrode (SHE), respectively, [11] while the CB and VB energies of Bi 2 S 3 are 0.09-0.12 and 1.41-1.47 V versus SHE, respectively, [12] which means that Bi 2 S 3 can form a type-II heterostructure with ZP. [13] When Bismuth (Bi)-based nanomaterials (NMs) are widely used for computed tomography (CT) imaging guided photothermal therapy, however, the photodynamic property is hardly exhibited by these NMs due to the fast electron-hole recombination within their narrow bandgap. Herein, a sophisticated nanosystem is designed to endow bismuth sulfide (Bi 2 S 3 ) nanorods (NRs) with potent photodynamic property. Zinc protoporphyrin IX (ZP) is linked to Bi 2 S 3 NRs through a thermoresponsive polymer to form BPZP nanosystems. The stretching ZP could prebind to the active site of heme oxygenase-1 overexpressed in cancer cells, suppressing the cellular antioxidant defense capability. Upon NIR laser irradiation, the heat released from Bi 2 S 3 NRs cou...

Engineering of bioactive metal sulfide nanomaterials for cancer therapy

“…In addition to CuS NCs, the non-aqueous solvothermal approach was well-established in the preparation of Bi 2 S 3 NPs [ 49 – 51 , 53 ]. The MeSNs prepared by this approach usually have uniform particle sizes and good dispersion qualities [ 48 – 50 , 52 ]. However, the non-aqueous solvothermal approach also has certain flaws.…”

“…On the basis of this feature, Cheng et al constructed smart Bi 2 S 3 nanorods (Bi 2 S 3 NRs) with a potent photodynamic property (Fig. 11 a) [ 50 ]. Zinc protoporphyrin IX (ZP) was associated with Bi 2 S 3 NRs through a thermo-responsive polymer to prepare Bi 2 S 3 NR-P(NIPAM- co -AM)-ZP-Pep nanosystems (BPZP).…”

Zinc and Autophagy in Age-Related Macular Degeneration

“…Zinc protoporphyrin (ZPP) is a zinc compound present in trace amounts in red blood cells during heme synthesis (reviewed in [96]). In normal conditions, iron chelates with protoporphyrin, but in iron deficiency or impaired iron metabolism, zinc takes the role of iron, resulting in increased formation of ZPP.…”

Zinc Sulfide-Based Hybrid Exosome-Coated Nanoplatform for Targeted Treatment of Glioblastoma in an Orthotopic Mouse Glioblastoma Model

“…CB (e − ) reacts with oxygen, and initiate the reduction process and produces OH • radical. [12] More importantly, in acidic microenvironment of tumor and especially lysosome, ZnS would produce hydrogen sulfide (H2S). [13] H2S, similar to carbon monoxide (CO) and nitric oxide (NO) as an endogenous gaseous transmitter, is known to play a crucial role in physiological and pathophysiological processes.…”

“…And the conduction band (e - ) reacts with oxygen to initiate a reduction process to produce 1 O 2 radicals. [12]…”