Dataset Information

Aggregation-Induced Emission (AIE) Polymeric Micelles for Imaging-Guided Photodynamic Cancer Therapy.

ABSTRACT: Photodynamic therapy (PDT) is a noninvasive treatment for selectively killing malignant tumor cells. The photosensitizer is a necessary component of photodynamic nanomedicine. Many efforts have been made to develop new photosensitizers for efficient cancer photodynamic therapy. In this work, we report a novel nano photosensitizer, polymeric micelles (AIE-M) with aggregation induced emission characteristic, for photodynamic cancer therapy. AIE-M with sub-20 nm particle size is prepared by the self-assembly of salicylaldazine-incorporated amphiphilic polymer (AIE-1), which can produce reactive oxygen species (ROS) with light irradiation in solution. After uptake by cancer cells, AIE-M can specially sojourn in plasma membranes of cancer cells at the early stage and predominantly accumulate in the mitochondria of cancer cell at the late stage. The phototoxicity of AIE-M, resulting from the generation of intracellular ROS with light irradiation, can efficiently cause cancer cells death by apoptosis and necrosis. The advantages of AIE-M as a nano photosensitizer include the small size, highly colloidal stability in the process of preparation and storage, and high cell penetration. The ultra-low Critical Micelle Concentration (CMC) of AIE-1, negligible dark toxicity and super phototoxicity of AIE-M suggest its promising potential for image-guided PDT.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6266309 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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Aggregation-Induced Emission (AIE) Polymeric Micelles for Imaging-Guided Photodynamic Cancer Therapy.

Zhang Yang Y Wang Cai-Xia CX Huang Shi-Wen SW

Nanomaterials (Basel, Switzerland) 20181107 11

Photodynamic therapy (PDT) is a noninvasive treatment for selectively killing malignant tumor cells. The photosensitizer is a necessary component of photodynamic nanomedicine. Many efforts have been made to develop new photosensitizers for efficient cancer photodynamic therapy. In this work, we report a novel nano photosensitizer, polymeric micelles (AIE-M) with aggregation induced emission characteristic, for photodynamic cancer therapy. AIE-M with sub-20 nm particle size is prepared by the sel ...[more]

PMID: 30405085

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Project description:Photosensitizer (PS) serves as the central element of photodynamic therapy (PDT). The use of common nanoparticles (NPs) for PDT has typically been rendered less effective by the undesirable aggregation-caused quenching (ACQ) effect, resulting in quenched fluorescence and reduced reactive oxygen species (ROS) generation that diminish the imaging quality and PDT efficacy. To overcome the ACQ effect and to enhance the overall efficacy of PDT, herein, integrin ???3-targeted organic nanodots for image-guided PDT were designed and synthesized based on a red emissive aggregation-induced emission (AIE) PS. Methods: The TPETS nanodots were prepared by nano-precipitation method and further conjugated with thiolated cRGD (cRGD-SH) through a click reaction to yield the targeted TPETS nanodots (T-TPETS nanodots). Nanodots were characterized for encapsulation efficiency, conjugation rate, particle size, absorption and emission spectra and ROS production. The targeted fluorescence imaging and antitumor efficacy of T-TPETS nanodot were evaluated both in vitro and in vivo. The mechanism of cell apoptosis induced by T-TPETS nanodot mediated-PDT was explored. The biocompatibility and toxicity of the nanodots was examined using cytotoxicity test, hemolysis assay, blood biochemistry test and histological staining. Results: The obtained nanodots show bright red fluorescence and highly effective 1O2 generation in aggregate state. Both in vitro and in vivo experiments demonstrate that the nanodots exhibit excellent tumor-targeted imaging performance, which facilitates image-guided PDT for tumor ablation in a hepatocellular carcinoma model. Detailed analysis reveals that the nanodot-mediated PDT is able to induce time- and concentration-dependent cell death. The use of PDT at a high PDT intensity leads to direct cell necrosis, while cell apoptosis via the mitochondria-mediated pathway is achieved under low PDT intensity. Conclusion: Our results suggest that well-designed AIE nanodots are promising for image-guided PDT applications.

Project description:meta-Tetra(hydroxyphenyl)chlorin (mTHPC) is one of the most potent second-generation photosensitizers, clinically used for photodynamic therapy (PDT) of head and neck squamous cell carcinomas. However, improvements are still required concerning its present formulation (i.e., Foscan, a solution of mTHPC in ethanol/propylene glycol (40:60 w/w)), as mTHPC has the tendency to aggregate in aqueous media, e.g., biological fluids, and it has limited tumor specificity. In the present study, polymeric micelles with three different diameters (17, 24, and 45 nm) based on benzyl-poly(?-caprolactone)-b-poly(ethylene glycol) (PCLn-PEG; n = 9, 15, or 23) were prepared with mTHPC loadings ranging from 0.5 to 10 wt % using a film-hydration method as advanced nanoformulations for this photosensitizer. To favor the uptake of the micelles by cancer cells that overexpress the epidermal growth factor receptor (EGFR), the micelles were decorated with an EGFR-targeted nanobody (named EGa1) through maleimide-thiol chemistry. The enhanced binding of the EGFR-targeted micelles at 4 °C to EGFR-overexpressing A431 cells, compared to low-EGFR-expressing HeLa cells, confirmed the specificity of the micelles. In addition, an enhanced uptake of mTHPC-loaded micelles by A431 cells was observed when these were decorated with the EGa1 nanobody, compared to nontargeted micelles. Both binding and uptake of targeted micelles were blocked by an excess of free EGa1 nanobody, demonstrating that these processes occur through EGFR. In line with this, mTHPC loaded in EGa1-conjugated PCL23-PEG (EGa1-P23) micelles demonstrated 4 times higher photocytotoxicity on A431 cells, compared to micelles lacking the nanobody. Importantly, EGa1-P23 micelles also showed selective PDT against A431 cells compared to the low-EGFR-expressing HeLa cells. Finally, an in vivo pharmacokinetic study shows that after intravenous injection, mTHPC incorporated in the P23 micelles displayed prolonged blood circulation kinetics, compared to free mTHPC, independently of the presence of EGa1. Thus, these results make these micelles a promising nanomedicine formulation for selective therapy.

Dataset Information

Aggregation-Induced Emission (AIE) Polymeric Micelles for Imaging-Guided Photodynamic Cancer Therapy.

Publications

Aggregation-Induced Emission (AIE) Polymeric Micelles for Imaging-Guided Photodynamic Cancer Therapy.

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