Oxygen-independent combined photothermal/photodynamic therapy delivered by tumor acidity-responsive polymeric micelles

A Porous Au@Rh Bimetallic Core–Shell Nanostructure as an H2O2‐Driven Oxygenerator to Alleviate Tumor Hypoxia for Simultaneous Bimodal Imaging and Enhanced Photodynamic Therapy

“…Semiquantitative analysis of the positive hypoxic area and microvessel density clearly revealed that Au@Rh‐CM and Au@Rh‐ICG‐CM could efficiently relieve tumor hypoxia without obvious alteration of tumor vasculature (Figure 5f and Figure S26b, Supporting Information). To determine whether replenishment of O 2 in tumors was able to elevate the ROS level, dihydroethidium (DHE) probe, which can be oxidized into ethidium by intracellular ROS and then intercalate into DNA to produce red fluorescence, [ 54 ] was used to stain frozen sections of tumors. As shown in Figure S27 (Supporting Information), strong red fluorescence was observed in tumors treated with Au@Rh‐ICG‐CM and 808‐nm laser irradiation, confirming a high level of ROS generation.…”

Rational design of block copolymer self-assemblies in photodynamic therapy

“…PIC with PS HUVEC and lung carcinoma, in vitro [46,47] poly(ethylene oxide)-block-poly(α,β-aspartic acid)/poly([5-aminopentyl]-α,β-aspartamide) -lung carcinoma, in vitro [48] poly(ethylene oxide)-block-poly(α,β-aspartic acid) PIC with PS lung carcinoma, in vitro [49] poly(N-methyl-2-vinylpyridinium iodide)-block-poly(ethylene oxide) PIC with PS - [50,51] [64] poly(oligo(ethylene oxide)methyl ether methacrylate)-block-poly(ʟ-lysine) O 2 production image-guided (FI), liver and breast cancer, in vitro [65] methoxy-poly(ethylene oxide)-block-poly(ε-caprolactone)-benzyl degradation macrophages and endothelial cells, in vitro [40] poly(ethylene oxide)-block-poly(ε-caprolactone) degradation colon cancer and carcinoma, in vitro [37,66,67] poly(ethylene glycol)-block-poly(lactic acid) degradation [38] poly(ethylene glycol)-block-poly(ᴅ,ʟ-lactide-co-benzyl glycidyl ether) degradation macrophage and kidney cells, in vitro [45] poly(ethylene glycol)-block-poly(ε-caprolactone)-block- aliphatic polyesters, based for instance on ε-caprolactone or lactic acid [36][37][38][39][40][41]. In particular, the degradation of polyesters in vivo, a combination of both hydrolytic and enzymatic processes, makes them a first choice for the controlled delivery of drugs [42].…”

“…Piperidine groups for example possess a pK a value close to the acidity of tumor tissues and exhibit a transition from hydrophobic at pH 7.4 to hydrophilic at pH 6.8. As a consequence, micelles increase their diameter and ζ-potential values switch from negative to positive thus accelerating cellular internalization [36]. Poly ion complexes formed thanks to electrostatic interactions between positively charged weak bases and negatively charged weak acids are ideal pH-responsive nanocarriers.…”

“…Doxorubicin or camptotecin, the most frequently used chemotherapeutic molecules, can be encapsulated [73,87,96,115] or chemically linked [80,90,93] to the polymer backbone and released under a precise stimulus. Chlorin-e6 [80], ICG [78], IR825 [80], IR 780 [106] or cypate [36,115] or pheophorbide [87] have been employed for the photothermal effect.…”

“…In [97] ( Figure 6d) and [104] ( Figure 6a) the photosensitizer was covalently linked to the polymer backbone; in both cases face-to-face H-type aggregation took place to some extent, nevertheless the higher oxygen concentration compensated it and singlet oxygen production efficiency was improved. Endoperoxides can be selected as a chemical source of singlet oxygen produced via thermal cycloreversion in an oxygen-independent manner [36,106]. This was possible thanks to the co-encapsulated cypate [36] or IR780 [106], which could induce hyperthermia through NIR irradiation.…”