Cell-Specific and pH-Activatable Rubyrin-Loaded Nanoparticles for Highly Selective Near-Infrared Photodynamic Therapy against Cancer

Abstract

Spatiotemporal control of singlet oxygen ((1)O2) release is a major challenge for photodynamic therapy (PDT) against cancer with high therapeutic efficacy and minimum side effects. Here a selenium-rubyrin (NMe2Se4N2)-loaded nanoparticle functionalized with folate (FA) was designed and synthesized as an acidic pH-activatable targeted photosensitizer. The nanoparticles could specifically recognize cancer cells via the FA-FA receptor binding and were selectively taken up by cancer cells via receptor-mediated endocytosis to enter lysosomes, in which NMe2Se4N2 was activated to produce (1)O2. The pH-controllable release of (1)O2 specially damaged the lysosomes and thus killed cancer cells in a lysosome-associated pathway. The introduction of selenium into the rubyrin core enhanced the (1)O2 generation efficiency due to the heavy atom effect, and the substitution of dimethylaminophenyl moiety at meso-position led to the pH-controllable activation of NMe2Se4N2. Under near-infrared (NIR) irradiation, NMe2Se4N2 possessed high singlet oxygen quantum yield (ΦΔ) at an acidic pH (ΦΔ = 0.69 at pH 5.0 at 635 nm) and could be deactivated at physiological pH (ΦΔ = 0.06 at pH 7.4 at 635 nm). The subcellular location-confined pH-activatable photosensitization at NIR region and the cancer cell-targeting feature led to excellent capability to selectively kill cancer cells and prevent the damage to normal cells, which greatly lowered the side effects. Through intravenous injection of FA-NMe2Se4N2 nanoparticles in tumor-bearing mice, tumor elimination was observed after NIR irradiation. This work presents a new paradigm for specific PDT against cancer and provides a new avenue for preparation of highly efficient photosensitizers.

Synthesis of Iron Nanometallic Glasses and Their Application in Cancer Therapy by a Localized Fenton Reaction

“…Va rious morphological characteristics of ROS-induced cell apoptosis,s uch as cell-membrane damage and nuclei shrinkage,w ere observed two hours after coincubation, which were similar to the well-defined cellular morphology changes observed after the administration of PDT. [19] Furthermore,magnetic targeting and the retention of the AFeNPs lead to selective anticancer effects ( Figure S15). These results confirm that the AFeNPs,h ydrogen peroxide, and acidic conditions act synergistically to kill cells,implying that AFeNP-induced specific CDT of tumors,w hich are inherently mildly acidic and over-produce hydrogen peroxide, should be possible.…”

Intracellular Modulation of Excited‐State Dynamics in a Chromophore Dyad: Differential Enhancement of Photocytotoxicity Targeting Cancer Cells

“…Earlier examples [4] made use of pH differences between the extracellular medium of the tumors and normal tissues. The difference (1-1.5 pH units) is actually found in the extracellular environment, not in the cytoplasm of the cells, [5] although the distinction is somewhat blurred in the current literature.…”

A charge-reversible nanocarrier using PEG-PLL(-<em>g</em>-Ce6, DMA)-PLA for photodynamic therapy

“…10,11 In particular, environmentally responsive nanoparticles have attracted much attention in PDT for their potential to reduce toxicity, their enhanced permeability and retention (EPR) effects that allow passive targeting, and their ability to control the release of photosensitizers through tumor extracellular pH or endosomal pH. [12][13][14] In the present study, we prepared a surface charge-reversible, stable nanoplatform to maximize the therapeutic effects of PDT. It was reported that nanoparticles with a positive charge can enhance the cellular uptake of therapeutic agents through electrostatic interaction with the negatively charged cell membrane.…”