Energy-Efficient and Effective MCF-7 Cell Ablation and Electrothermal Therapy Enabled by M13-WS2-PEG Nanostructures.

Thermal agents (TAs) have exhibited promise in clinical tests when utilized in cancer thermal therapy (TT). While rapid degradation of TAs may address safety concerns, it limits the thermal stability required for effective treatment. TAs, which possess exceptional thermal stability, experience gradual deterioration. There are few approaches that effectively address the trade-off between improving thermal stability and simultaneously boosting material deterioration. Here, we control the thermal character of tungsten disulfide (WS2)-based 2D materials by utilizing an M13 phage through Joule heating (the M13-WS2-PEG nanostructures were generated and termed a tripartite (T) nanostructure), and developed a T nanostructure-driven TT platform (we called it T-TT) for efficient thermal ablation of clinically relevant MCF-7 cells. A relative cell viability of ~59% was achieved, as well as onset time of degradation of ~0.5 week. The T-TT platform also discloses an energy density of 5.9 J/mL. Furthermore, the phage-conjugated WS2 can be utilized to achieve ultrasound imaging for disease monitoring. Therefore, this research not only presents a thermal agent that overcomes TA limitations, but also demonstrates a practical application of WS2-type material system in ultra-energy efficient and effective cancer therapy.

Shape complementarity processes for ultrashort-burst sensitive M13-PEG-WS2-powered MCF-7 cancer cell sensors.

Biomarkers have the potential to be utilized in disease diagnosis, prediction and monitoring. The cancer cell type is a leading candidate for next-generation biomarkers. Although traditional digital biomolecular sensor (DBS) technology has shown to be effective in assessing cell-based interactions, low cell-population detection of cancer cell types is extremely challenging. Here, we controlled the electrical signature of a two-dimensional (2D) nanomaterial, tungsten disulfide (WS2), by utilizing a combination of the Phage-integrated Polymer and the Nanosheet (PPN), viz., the integration of the M13-conjugated polyethylene glycol (PEG) and the WS2, through shape-complementarity phenomena, and developed a sensor system, i.e., the Phage-based DBS (P-DBS), for the specific, rapid, sensitive detection of clinically-relevant MCF-7 cells. The P-DBS attains a detection limit of 12 cells per µL, as well as a contrast of 1.25 between the MCF-10A sample signal and the MCF-7 sample signal. A reading length of 200 µs was further achieved, along with a relative cell viability of ∼100% for both MCF-7 and MCF-10A cells and with the PNN. Atomistic simulations reveal the structural origin of the shape complementarity-facilitated decrease in the output impedance of the P-DBS. The combination of previously unreported exotic sensing materials and digital sensor design represents an approach to unlocking the ultra-sensitive detection of cancer cell types and provides a promising avenue for early cancer diagnosis, staging and monitoring.

Gemcitabine interacts with carbonate apatite with concomitant reduction in particle diameter and enhancement of cytotoxicity in breast cancer cells.

Substantial amount of research has been done in recent decades for the development of nanoparticle systems to selectively deliver drugs to cancer cells for concurrently enhancing and reducing anti-cancer and off-target effects, respectively. pH-sensitive carbonate apatite (CA) was originally developed for efficient and targeted delivery of DNA, siRNA and proteins to various cancer cell lines. Recently, the CA particles were employed to deliver anti-cancer drugs, cyclophosphamide, doxorubicin and methotrexate to cancer cells. Here, we report on the fabrication and characterization of gemcitabine- loaded CA particles, followed by the evaluation of their roles in enhancement of cytotoxicity in two human and one murine breast cancer cell lines. HPLC was performed to measure binding efficiency of the drug to the apatite particles whereas particle size and zeta potential were evaluated to characterize drug/apatite complex. Depending on the initial doses of the drug, its bind binding affinity towards the particles varied from 3.85% to 4.45%. The particle size was found to surprisingly decrease with an increase of the initial drug concentration. In vitro chemosensitivity assay revealed that apatite/drug nanoparticle complexes presented significantly higher cytotoxicity to breast cancer cells compared to free drugs, which could be correlated with the enhanced cellular uptake of the small size drug-loaded particles through endocytosis compared to the passive diffusion of the free drug.