A Tailored Multifunctional Anticancer Nanodelivery System for Ruthenium‐Based Photosensitizers: Tumor Microenvironment Adaption and Remodeling

Abstract

Ruthenium complexes are promising photosensitizers (PSs), but their clinical applications have many limitations. Here, a multifunctional nano‐platform PDA‐Pt‐CD@RuFc formed by platinum‐decorated and cyclodextrin (CD)‐modified polydopamine (PDA) nanoparticles (NPs) loaded with a ferrocene‐appended ruthenium complex (RuFc) is reported. The NPs can successfully deliver RuFc to the tumor sites. The release of RuFc from the NPs can be triggered by low pH, photothermal heating, and H2O2. The combined photodynamic and photothermal therapy (PDT‐PTT) mediated by PDA‐Pt‐CD@RuFc NPs can overcome the hypoxic environment of tumors from several aspects. First, the platinum NPs can catalyze H2O2 to produce O2. Second, vasodilation caused by photothermal heating can sustain the oxygen supplement. Third, PDT exerted by RuFc can also occur through the non‐oxygen‐dependent Fenton reaction. Due to the presence of PDA, platinum NPs, and RuFc, the nanosystem can be used in multimodal imaging including photothermal, photoacoustic, and computed tomography imaging. The NPs can be excited by the near‐infrared two‐photon light source. Moreover, the combined treatment can improve the tumor microenvironments to obtain an optimized combined therapeutic effect. In summary, this study presents a tumor‐microenvironment‐adaptive strategy to optimize the potential of ruthenium complexes as PSs from multiple aspects.

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

“…In fact, the Fenton reaction is very commonly used in the design and synthesis of nano-photosensitizers. Currently, some studies have used the Fenton reaction to increase the concentration of O 2 [ 174 ] or hydroxyl radicals[ 175 ] in the tumor microenvironment, and others used it to directly kill CSCs. PDT combined with the Fenton reaction[ 176 ] is a feasible treatment method for CSCs showing strong drug resistance.…”

Photophysics and Cell Uptake of Self-Assembled Ru(II)Polypyridyl Vesicles

“…Nanocarriers are a widely studied tool in drug delivery, and an attractive proposition both for transport of ruthenium probes across the cell membrane and for achieving targeting. Indeed, one may amplify the intensity of the luminophore through incorporation of ruthenium polypyridyl complexes into amphiphilic nanovectors (Ellahioui et al, 2019 ; Liang et al, 2020 ; Saeed et al, 2020 ).…”

Recent advances in innovative strategies for enhanced cancer photodynamic therapy

“…Another strategy for designing O 2 -supply PDT platforms is to use Pt NPs. Liang et al 81 prepared a nano-multifunctional platform (PDA-Pt-CD@RuFc) by loading Pt-modified and cyclodextrin (CD)-decorated polydopamine (PDA) NPs with a Ruthenium (II) complex (RuFc). The Pt NPs catalyzed the generation of O 2 from H 2 O 2 , and then RuFc photoactivated O 2 to produce 1 O 2 for PDT.…”