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.

Development of pH‐responsive cyclodextrin nanoparticles for tumor‐specific photodynamic therapy

“…Subsequently, the treated cells were monitored using a Nikon microscope equipped with a visible and near-infrared (VNIR) hyperspectral camera (CytoViva, Auburn, Alabama). 26…”

“…To determine the phototoxicities of the γCD-based NPs, the generation of singlet oxygen from the NP samples at pH 7.4 and 6.8 was measured using fluorescent 9,10-dimethylanthracene (DMA, as a marker for singlet oxygen generation). 18,26 As shown in Figure 4B (a physiological pH) and 6.8 (an tumor acidic extracellular pH). 18,19 The average fluorescence intensity (indicating cellular uptake of fluo- Figure 4B).…”

Transferrin-Conjugated pH-Responsive γ-Cyclodextrin Nanoparticles for Antitumoral Topotecan Delivery

“…Furthermore, we evaluated the cell apoptosis of both the MDA-MB-231 and CHO-K1 cells treated with NPs (equivalent to TPT 10 µg/mL) or free TPT (10 µg/mL) at 37 • C for 4 h. These tumor cells were stained with Annexin V-FITC and propidium iodide (PI) for 15 min at 25 • C and then analyzed using the In vivo experiments were conducted using 6-8 weeks old female BALB/c mice (Orient Bio Inc., Seoul, Korea). The nude mice were maintained under the guidelines of approved protocol (code: CUK-IACUC-2020-011, 06-08-2020) from the Institutional Animal Care and Use Committee (IACUC) of the Catholic University of Korea (Republic of Korea) [27][28][29][30][31][32]37].…”

“…These results indicate that the NPs with Tf ligands were efficiently endocytosed to MDA-MB-231 tumor cells [16,[32][33][34][35][36][37], which was also readily apparent in the confocal image results. Figure 5b shows that the apoptotic cell population (Q2 and Q3) [16,30] of MDA-MB-231 cells treated with γCDP-(DMA/PEG-Tf) NPs was 55.7%, but those of MDA-MB-231 cells treated with γCDP-(DMA/PEG) NPs, γCDP-(PEG-Tf) NPs, and γCDP-(PEG) NPs were 27.8%, 41.6%, and 18.2%, respectively. These results were comparable to those of the TPT-loaded NP samples, in which relatively low cell cytotoxicity to normal CHO-K1 cells (Figure 5a), most likely due to their reduced cellular uptake (Figure 4b), was observed.…”

“…(c) Cell viability of MDA-MB-231 tumor cells treated with each sample (1-100 μg/mL, without TPT) at pH 7.4 for 24 h (n = 7). In addition, to verify the degree to which the multifunctionality of γCDP-(DMA/PEG-Tf) NPs affected in vivo tumor ablation, we investigated the in vivo pharmaceutical potential of γCDP-(DMA/PEG-Tf) NPs using MDA-MB-231 tumor-bearing BALB/c nude mice [27][28][29][30][31][32]37]. Here, the NP samples were intravenously administered to MDA-MB-231 tumor-bearing BALB/c nude mice, and their fluorescence images and in vivo antitumor efficacy were obtained.…”