Ce6-Modified Carbon Dots for Multimodal-Imaging-Guided and Single-NIR-Laser-Triggered Photothermal/Photodynamic Synergistic Cancer Therapy by Reduced Irradiation Power

Abstract

Photomediated cancer therapy, mainly including photothermal (PT) therapy (PTT) and photodynamic therapy (PDT), has attracted tremendous attention in recent years thanks to its noninvasive and stimuli-responsive features. The single mode of PTT or PDT, however, has obvious drawbacks, either requiring high-power laser irradiation to generate enough heat or only providing limited efficacy due to the hypoxia nature inside tumors. In addition, the reported synergistic PTT/PDT generally utilized two excitation sources to separately activate PTT and PDT, and the problem of high-power laser irradiation for PTT was still not well solved. Herein, a new concept, loading a small amount of photosensitizers onto a PTT agent (both of them can be triggered by a single-near-infrared (NIR) laser), was proposed to evade the shortcomings of PTT and PDT. To validate this idea, minute quantities of photosensitizer chlorin e6 (Ce6) (0.56% of mass) were anchored onto amino-rich red emissive carbon dots (RCDs) that possess superior photothermal (PT) character under 671 nm NIR laser (PT conversion efficiency to be 46%), and meanwhile the PDT of Ce6 can be activated by this laser irradiation as well. The findings demonstrate that Ce6-modified RCDs (named Ce6-RCDs) offer much higher cancer therapy efficacy under a reduced laser power density (i.e., 0.50 W cm–2 at 671 nm) in vitro and in vivo than the equivalent RCDs or Ce6 under the same irradiation conditions. Besides, the Ce6-RCDs also exhibit multimodal imaging capabilities (i.e., fluorescence (FL), photoacoustic (PA), and PT), which can be employed for guidance of the phototherapy process. This study suggests not only a strategy to enhance cancer phototherapy efficacy but also a promising candidate (i.e., Ce6-RCDs) for multimodal FL/PA/PT imaging-guided and single-NIR-laser-triggered synergistic PTT/PDT for cancers by a reduced irradiation power.

Recent advance of carbon dots in bio-related applications

“…The PEG-CuCDs could be an agent for FI, photothermal imaging, and photoacoustic imaging. Sun et al [87] conjugated Ce6 (Chlorin e6) onto the red emissive amino rich CDs to form Ce6-RCD, which exhibited red emission at~640 nm and photothermal conversion efficiency of 46% with 671 nm laser irradiation. The Ce6-RCD could be a multimodal bioimaging agent for FI, PT, and PA. Also, they (PEG-CuCDs and Ce6-RCDs) can be employed for photothermal and photodynamic therapy agents.…”

“…The CDs exhibited the emission at 640 nm with a decent PL QY of 22.9%, low toxicity, two-photon excited fluorescent and high photothermal conversion efficiency of 43.9% under irradiation of 671 nm laser. They prepared red emissive CDs from CA and PEI in the formamide and conjugated with Ce6 as a photosensitizer [87]. The Ce6-CDs complexes showed synergetic PTT and PDT effect under a single NIR laser (671 nm) source.…”

<p>Self-Assembly Nanoparticles for Overcoming Multidrug Resistance and Imaging-Guided Chemo-Photothermal Synergistic Cancer Therapy</p>

“…Typical examples include NIRF imaging, photoacoustic (PA) imaging, ultrasound (US) imaging, magnetic resonance (MR) imaging and positron emission tomography (PET) imaging. [20][21][22][23][24] Although traditional delivery formulations combined therapeutic agents and imaging agents into a nanoplatform, its potential toxicity, overly complicated design, and poor drug loading capacity of nanocarriers make this type of treatment far too impractical for clinical application. To solve this issue, nanotheranostics that are achieved directly from small molecules without any carrier have attracted great attention.…”

Graphene-modified CePO4 nanorods effectively treat breast cancer-induced bone metastases and regulate macrophage polarization to improve osteo-inductive ability

“…As compared with radiotherapy and chemotherapy, photothermal therapy (PTT) attracted increasing attention because of its highly e cient antitumor effect, precise spatial-temporal selectivity and no harm to healthy tissues and organs (17)(18)(19). A variety of photothermal agents, such as copper-palladium alloys (19), graphene (20), carbon dots (21), magnetic nanoparticles (22) and Cu7.2S4 Nanoparticles (23) were developed for tumour therapy. The near-infrared (NIR) laser irradiation signi cantly elevates the local temperatures around photothermal agents to kill cancer cells via hyperthermia, and inhibit the expression of the metastasis-related factors such as matrix metalloproteinase, twist and transforming growth factor-β1 (24).…”

“…The VEGF might activate MMP-9, which can induce migration and proliferation of angioblast; Arg-1, as one of the most effective growth factors involved in angioblast recruitment. The scaffold can inhibit the aggregation of pro-in ammatory macrophages and the formation of brous connective tissue between the bone tissue and prosthesis, which promotes the fusion of the scaffold material and osteoblasts (20,21).…”