Developing novel nanostructures and advanced nanotechnologies for cancer treatment has attracted ever-increasing interest. Electrothermal therapy offers many advantages such as high efficiency and minimal invasiveness, but finding a balance between increasing stability of the nanostructure state and, at the same time, enhancing the nanostructure biodegradability presents a key challenge. Here, we modulate the biodegradation process of two-dimensional-material-based nanostructures by using polyethylene glycol (PEG) via nanostructure disrupt-and-release effects. We then demonstrate the development of a previously unreported alternating current (AC) pulse WS2/PEG nanostructure system for enhancing therapeutic performance. A decrease in cell viability of ∼42% for MCF-7 cells with WS2/PEG was achieved, which is above an average of ∼25% for current electrothermal-based therapeutic methods using similar energy densities, as well as degradation time of the WS2 of ∼1 week, below an average of ∼3.5 weeks for state-of-the-art nanostructure-based systems in physiological media. Moreover, the incubation time of MCF-7 cells with WS2/PEG reached ∼24 h, which is above the average of ∼4.5 h for current electrothermal-based therapeutic methods and with the use of the amount of time harnessed to incubate the cells with nanostructures before applying a stimulus as a measure of incubation time. Material characterizations further disclose the degradation of WS2 and the grafting of PEG on WS2 surfaces. These WS2-based systems offer strong therapeutic performance and, simultaneously, maintain excellent biodegradability/biocompatibility, thus providing a promising route for the ablation of cancer.

A direct current (DC) resistance sensor based on two-dimensional (2D) molybdenum disulfide (MoS ₂ ) was developed to enable cancer cell-specific detection via micro-changes in the cancer cell membrane.

Promising results in clinical studies have been demonstrated by the utilization of electrothermal agents (ETAs) in cancer therapy. However, a difficulty arises from the balance between facilitating the degradation of ETAs, and at the same time, increasing the electrothermal performance/stability required for highly efficient treatment. In this study, we controlled the thermal signature of the MoS₂ by harnessing MoS₂ nanostructures with M13 phage (MNM) via the structural assembling (hydrophobic interaction) phenomena and developed a combined PANC-1 cancer cell–MNM alternating current (AC)-stimulus framework for cancer cell ablation and electrothermal therapy. A percentage decrease in the cell viability of ~23% was achieved, as well as a degradation time of 2 weeks; a stimulus length of 100 μs was also achieved. Molecular dynamics (MD) simulations revealed the assembling kinetics in integrated M13 phage–cancer cell protein systems and the structural origin of the hydrophobic interaction-enabled increase in thermal conduction. This study not only introduced an ‘ideal’ agent that avoided the limitations of ETAs but also provided a proof-of-concept application of MoS₂-based materials in efficacious cancer therapy.

A few-volt nanosecond alternating-current stimulation method with an increased number of pulses exploiting orientational-disordering processes.

The development of combined 2D-material-polymer-phage frameworks that can enhance cancer cell detection via the enhancement of electrical conductivity.

Clinical trials have generated encouraging outcomes for the utility of thermal agents (TAs) in cancer thermal therapy (TT). Although the fast breakdown of TAs alleviates safety concerns, it restricts the thermal stability necessary for effective treatment. TAs with excellent thermal stability, on the other hand, deteriorate slowly. Rare are the approaches that address the trade-off between high thermal stability and quick deterioration of TAs. Here we control the thermal signature of WS₂-type 2D materials by utilizing previously undescribed DOX–WS₂–PEG–M13 nanostructures (we term them D nanostructures) through Joule heating phenomena, and develop an integrated system for TT for enhancing thermal performance, and simultaneously, maintaining rapid degradation, and chemotherapy for efficacious treatment. A relative cell viability of ~ 50% was achieved by the D-based TT (DTT) configuration, as well as a 1 nM drug concentration. The D-driven chemotherapy (DCT) model also attains a relative cell viability of 80% for 1 nM drug concentration, while a 1-week degradation time was revealed by the D nanostructure. Theoretical studies elucidate the drug molecule–nanostructure and drug-on-nanostructure–solution interaction-facilitated enhancement in drug loading and drug release performance in DCT varieties. As a result, this work not only proposes a “ideal TA” that circumvents TA restrictions, but also enables proof-of-concept application of WS₂-based materials in chemotherapy-unified combination cancer therapy. Graphical Abstract