Incorporation of Ru(II) Polypyridyl Complexes into Nanomaterials for Cancer Therapy and Diagnosis

Abstract

Ru(II) metal center. [2] They absorb light and emit wavelength within the red and the near infrared (NIR) spectral regions and possess large Stokes shift, long luminescence lifetime, and potential twophoton (2P) absorption properties. These characteristics have made them highly desirable across numerous research fields such as catalysis, [3] solar energy, [4] sensors [5] and now across the biomedical field either in diagnostics as cellular imaging tools, luminescent probes of DNA structures or in therapy as new classes of anticancer drugs for chemotherapy and photosensitizers (PSs) for photodynamic therapy (PDT) or photoactivated chemotherapy (PACT). [6-11] Worthy of note, a Ru(II) polypyridyl compound (TLD1433) has recently entered phase II clinical trials in Canada for the treatment of nonmuscle invasive bladder cancer as a PS for PDT. [12] However, these complexes still suffer from some drawbacks such as poor water solubility, lack of targeting capability, nonspecific distribution, systemic toxicity and hence, low therapeutic index hampering their translation into the clinic. One strategy to address those medical challenges is to use nanomedicine. Nanomedicine is the application of sub-micron particles (i.e., nanoparticles) in the field of medicine. The materials used for the synthesis and/ or formulation of nanoparticles are extremely diverse, ranging from organic to inorganic molecules (Figure 1). [13] The unique features of nanoparticles including small size, high surface area, surface chemistry, water solubility and multifunctionality make them highly interesting for drug delivery purposes. [14,15] Owing to their size, nanoparticles can passively accumulate to solid tumors while sparing healthy cells thanks to the enhanced permeation and retention (EPR) effect. [16] The EPR effect exploits the abnormalities of tumor vasculature, namely hypervascularity, atypical vascular architecture, leaky vasculature, and lack of lymphatic drainage. This results in the efficient extravasation of nanoparticles from the tumor vasculature and their retention in the tumor interstitium. Therefore, drug incorporation into nanoparticles provides significant improvements in pharmacokinetics, solubility, toxicity, and biodistribution when compared to freely administered molecules, reducing adverse side effects observed with conventional medicine. However, to take full advantage of the EPR effect, nanoparticles must remain in circulation long enough for tumor accumulation. PEGylation, which refers to modification with poly(ethylene glycol) (PEG) chains or PEG copolymers (e.g., Jeffamine), is the most common strategy for imparting stealth properties to nanoparticles. [17] The presence of PEG enables steric stabilization Ru(II) polypyridyl complexes are compounds of great interest in cancer therapy due to their unique photophysical, photochemical, and biological properties. For effective treatment, they must be able to penetrate tumor cells effectively and selectively. The development of nanoscale carriers capable of delivering Ru(I...

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“…It depends on the laser-induced ability of photosensitizers (PSs) to transfer energy to oxygen dissolved in the tumor environment to generate cytotoxic singlet oxygen (O 1 2 ), which enabled successively causing cell death and mortality of immediate tumor tissues [5]. However, the PDT efficiency of solid tumors is mostly unsatisfying by issues involving the hydrophobic and hypoxic tumor microenvironment (TME) [6] and limited light penetrability [7].…”

A supramolecular photosensitizer derived from an Arene-Ru(II) complex self-assembly for NIR activated photodynamic and photothermal therapy

“…1A ). In order to enhance the tumor accumulation and biocompatibility in vivo, the FDA-approved Pluronic F127 (PEO-PPO-PEO) was used to encapsulate RuDA 47 – 49 , yielding nanoparticles RuDA-NPs (Fig. 1B ), which act as a highly efficient PDT/PTT dual-modal agent.…”

Antitumor Immune Response Triggered by Metal-Based Photosensitizers for Photodynamic Therapy: Where Are We?

“…Moreover, a current limitation of PDT is the skin photosensitivity caused by the accumulation of a PS in skin cells [30]. The use of nanoparticles that allows for a more specific delivery of PSs to tumor cells has been developed in recent years to address this limitation [31,32]. The light-dependent cytotoxicity of the PS is, therefore, at the base of the principle of PDT, which usually relies on the systemic intravenous injection of the PS.…”