Dataset Information

Poisonous Caterpillar-Inspired Chitosan Nanofiber Enabling Dual Photothermal and Photodynamic Tumor Ablation.

ABSTRACT: As caterpillars detect the presence of predators and secrete poison, herein, we show an innovative and highly effective cancer therapeutic system using biocompatible chitosan nanofiber (CNf) installed with a pH-responsive motif that senses tumor extracellular pH, pHe, prior to delivering dual-modal light-activatable materials for tumor reduction. The filamentous nanostructure of CNf is dynamic during cell interaction and durable in blood circulation. Due to its amine group, CNf uptakes a large amount of photothermal gold nanoparticles (AuNPs, >25 wt %) and photodynamic chlorin e6 (Ce6, >5 wt %). As the innovative CNf approaches tumors, cationic CNf effectively discharges AuNPs connected to the pH-responsive motif via electrostatic repulsion and selectively binds to tumor cells that are generally anionic, via the electrostatic attraction accompanied by CNf. We demonstrated via these actions that the endocytosed Ce6 (on CNf) and AuNPs (free from CNf) significantly elicited tumor cell death under light irradiation. As a result, the synergistic interplay of thermogenesis and photodynamic action was observed to switch on at the pHe, resulting in a striking reduction in tumor formation and growth rate upon light exposure.

SUBMITTER: Yu HS

PROVIDER: S-EPMC6631857 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Poisonous Caterpillar-Inspired Chitosan Nanofiber Enabling Dual Photothermal and Photodynamic Tumor Ablation.

Yu Hyeong Sup HS Park Hongsuk H Tran Thang Hong TH Hwang Sung Yeon SY Na Kun K Lee Eun Seong ES Oh Kyung Taek KT Oh Dongyeop X DX Park And Jeyoung AJ

Pharmaceutics 20190602 6

As caterpillars detect the presence of predators and secrete poison, herein, we show an innovative and highly effective cancer therapeutic system using biocompatible chitosan nanofiber (CNf) installed with a pH-responsive motif that senses tumor extracellular pH, pH<sub>e</sub>, prior to delivering dual-modal light-activatable materials for tumor reduction. The filamentous nanostructure of CNf is dynamic during cell interaction and durable in blood circulation. Due to its amine group, CNf uptake ...[more]

PMID: 31159476

Similar Datasets

Project description:The poor delivery of nanoparticles to target cancer cells hinders their success in the clinical setting. In this work, an alternative target readily available for circulating nanoparticles has been selected to eliminate the need for nanoparticle penetration in the tissue: the tumor blood vessels. A tumor endothelium-targeted nanoparticle (employing an RGD-containing peptide) capable of co-delivering two anti-vascular drugs (one anti-angiogenic drug and one vascular disruption agent) is here presented. Furthermore, the nanodevice presents two additional anti-vascular capabilities upon activation by Near-Infrared light: provoking local hyperthermia (by gold nanorods in the system) and generating toxic reactive oxygen species (by the presence of a photosensitizer). RGD-targeting is shown to increase uptake by HUVEC cells, and while the nanoparticles are shown not to be toxic for these cells, upon Near-Infrared irradiation their almost complete killing is achieved. The combination of all four therapeutic modalities is then evaluated in an ex ovo fibrosarcoma xenograft model, which shows a significant reduction in the number of blood vessels irrigating the xenografts when the nanoparticles are present, as well as the destruction of the existing blood vessels upon irradiation. These results suggest that the combination of different anti-vascular therapeutic strategies in a single nanocarrier appears promising and should be further explored in the future. STATEMENT OF SIGNIFICANCE MVR2019: The combination of antivascular drugs with different mechanisms of action (such as antiangiogenic drugs and vascular disruption agents) has been recently proposed as a promising approach to maximize the therapeutic potential of anti-vascular therapeutics. Given the capacity of nanoparticles to co-deliver different drugs in optimizable ratios, nanomedicine appears to have a huge potential for the development of this kind of multimodal antivascular. To showcase this, an multimodal anti-vascular nanodevice for cancer therapy is here presented. This tumor endothelium-targeted nanosystem is capable of co-delivering two anti-vascular drugs (anti-angiogenic and vascular disruption agent) while also providing two additional therapeutic modalities that can be activated by Near-Infrared light: provoking local hyperthermia (photothermal therapy) and generating toxic reactive oxygen species (photodynamic therapy).

Project description:Photodynamic therapy (PDT) is a treatment in which photoactive compounds delivered to cancerous tissues are excited with light and then transfer the absorbed energy to adjacent tissue oxygen molecules to generate toxic singlet oxygen (1O2). As 1O2 is produced only where light and photosensitizers (PSs) are combined, PDT holds promise as a minimally invasive, highly selective treatment for certain cancers. The practical application of PDT requires easily synthesized, water-soluble PSs that have low dark toxicities, high 1O2 quantum yields, and efficient absorption of 650-850 nm near-infrared (NIR) light, which deeply penetrates tissue. We recently developed a linear tetrapyrrole metal complex, Pd[DMBil1]-PEG750, that meets most of these criteria. This complex is remarkably effective as a PS for PDT against triple-negative breast cancer (TNBC) cells but, critically, it does not absorb NIR light, which is necessary to treat deeper tumors. To enable NIR activation, we synthesized a new derivative, Pd[DMBil1]-PEG5000-SH, which bears a thiol functionality that facilitates conjugation to NIR-absorbing gold nanoshells (NSs). Upon excitation with pulsed 800 nm light, NSs emit two-photon-induced photoluminescence spanning 500-700 nm, which can sensitize the attached PSs to initiate PDT. Additionally, NSs produce heat upon 800 nm irradiation, endowing the NS-PS conjugates with an auxiliary photothermal therapeutic (PTT) capability. Here, we demonstrate that NS-PS conjugates are potent mediators of NIR-activated tandem PDT/PTT against TNBC cells in vitro. We show that Pd[DMBil1]-PEG5000-SH retains the photophysical properties of the parent Pd[DMBil1] complex, and that NS-PS generate 1O2 under pulsed 800 nm irradiation, confirming activation of the PSs by photoluminescence emitted from NSs. TNBC cells readily internalize NS PS conjugates, which generate reactive oxygen species in the cells upon pulsed NIR irradiation to damage DNA and induce apoptosis. Together, these findings demonstrate that exploiting photoluminescent NSs as carriers of efficient Pd[DMBil1] PSs is an effective strategy to enable NIR light-activated tandem PDT/PTT.

Dataset Information

Poisonous Caterpillar-Inspired Chitosan Nanofiber Enabling Dual Photothermal and Photodynamic Tumor Ablation.

Publications

Poisonous Caterpillar-Inspired Chitosan Nanofiber Enabling Dual Photothermal and Photodynamic Tumor Ablation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets