Bacteria‐Assisted Selective Photothermal Therapy for Precise Tumor Inhibition

Abstract

Photothermal therapy (PTT) has drawn extensive research attention as a promising approach for tumor treatment. In this study, a bacteria-assisted strategy relying on the selective reduction of perylene diimide derivative based supramolecular complex (CPPDI) to radical anions (RAs) by Escherichia coli in hypoxic tumors is developed to realize highly precise PTT of tumors. Noninvasive E. coli are first injected intravenously for selectively accumulating and replicating in the tumor due to the hypoxia tropism. Then, CPPDI is loaded in a peptide-hybrid matrix metalloproteinase-2 (MMP-2) responsive liposome (MRL) and injected intravenously. After accumulated and released from MRL in the tumor where MMP-2 is overexpressed, CPPDI is reduced by E. coli in the hypoxic tumor environment to produce CPPDI RAs (CRAs), which serve as effective photothermal agents for tumor cells thermal ablation under near-infrared light irradiation. Since E. coli accumulate and grow in tumor sites selectively, this strategy accurately limits the production of CRAs in tumors for highly selective PTT, which will find great potential for precise tumor inhibition.

“Trojan Horse” Salmonella Enabling Tumor Homing of Silver Nanoparticles via Neutrophil Infiltration for Synergistic Tumor Therapy and Enhanced Biosafety

“…Compared with the normal mice, a bright fluorescence was observed in tumor tissue at 48 h postinjection of S.t -ΔpG lux (Figure E). We further stained the tumor tissue by using a hypoxia biomarker of carbonic anhydrase-IX (CA9) with green fluorescence (Figure F) . From the merged image, the fluorescence of S.t -ΔpG lux and CA9 was highly overlaid, demonstrating the preferential colonization of S.t -ΔpG lux within the hypoxic tumor region.…”

Aptamer-assisted tumor localization of bacteria for enhanced biotherapy

“…[15] Alternatively, decoration with various types of substrates on bacterial surface, such as synthetic nanoparticles and therapeutic drugs, has been exploited to enhance antitumor activity. [16][17][18][19] We have recently wrapped with extra coatings to retain bacterial viability under unfriendly external conditions. [20][21][22][23][24] For instance, bacteria decorated with a stealth coating can decrease their elimination by macrophages, which subsequently prolongs blood circulation following systemic injection.…”

Tumor-targeting inorganic nanomaterials synthesized by living cells

“…E. coli is one of the widely studied bacterial species for nanomaterial biosynthesis, with nely controllable genomic and metabolic functions. [72][73][74][75] Aer being engineered to express MT and/or PCS, recombinant E. coli cells were incubated with various metal ions, including semiconducting (Cd, Se, Zn, Te), alkali-earth (Cs, Sr), magnetic (Fe, Co, Ni, Mn), and noble (Au, Ag) metals and rare-earth uorides (Pr, Gd), to synthesize the corresponding metal NPs. 21 In the synthesis processes, MTs are capable of binding heavy metals (i.e., Cu, Cd, and Zn), while the metal-binding peptide phytochelatin (PC) synthesized by PCS plays a signicant role in heavy-metal detoxication processes, as a family of cysteinerich, thiol-reactive peptides that bind several toxic metals (i.e., Cu, Zn, Cd, Hg, and Pb).…”