DNA–SWCNT Biosensors Allow Real-Time Monitoring of Therapeutic Responses in Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly desmoplastic cancer with limited treatment options. There is an urgent need for tools that monitor therapeutic responses in real time. Drugs such as gemcitabine and irinotecan elicit their therapeutic effect in cancer cells by producing hydrogen peroxide (H 2 O 2). In this study, specific DNA-wrapped singlewalled carbon nanotubes (SWCNT), which precisely monitor H 2 O 2 , were used to determine the therapeutic response of PDAC cells in vitro and tumors in vivo. Drug therapeutic efficacy was evaluated in vitro by monitoring H 2 O 2 differences in situ using reversible alteration of Raman G-bands from the nanotubes. Implantation of the DNA-SWCNT probe inside the PDAC tumor resulted in approximately 50% reduction of Raman G-band intensity when treated with gemcitabine versus the pretreated tumor; the Raman G-band intensity reversed to its pretreatment level upon treatment withdrawal. In summary, using highly specific and sensitive DNA-SWCNT nanosensors, which can determine dynamic alteration of hydrogen peroxide in tumor, can evaluate the effectiveness of chemotherapeutics. Significance: A novel biosensor is used to detect intratumoral hydrogen peroxide, allowing real-time monitoring of responses to chemotherapeutic drugs.

Activatable NIR‐II Fluorescent Probes Applied in Biomedicine: Progress and Perspectives

“…Current fabrication of NIR‐II AFPs is mainly centered on NIR‐II fluorophores including rare earth‐doped nanoparticles (RENPs), [32–35] quantum dots (QDs), [26,36–39] single‐walled carbon nanotubes (SWNTs), [40–42] small molecule dyes, [16,43–46] conjugated polymers [47–50] and gold nanoclusters (AuNCs) [51–53] . In this section, the representative design and application of currently available NIR‐II fluorophores are introduced.…”

“…After that, more and more SWNTs were applied for biomedicine researches. For example, Bhattacharya's group developed a specific DNA‐wrapped SWNTs that could accurately monitor H 2 O 2 for determining the effect of cancer treatment [40] . DNA‐SWNTs hybrids could be regarded as an effective tool for evaluating the efficacy of chemotherapeutic drugs.…”

Transcutaneous Measurement of Essential Vitamins Using Near‐Infrared Fluorescent Single‐Walled Carbon Nanotube Sensors

“…There has been significant interest in developing sensors that can operate within the human body, communicating information on the human endocrine system, steroidogenesis hormone signaling, [ 10 ] and drug efficacy. [ 11 ] As analytes, vitamins such as riboflavin and ascorbic acid are frequently utilized in a range of biomedical applications as drug delivery targets in and of themselves, [ 12,13 ] tracers for physiological fluid flow, [ 14 ] and as pharmaceutical excipients. [ 15,16 ] The ability for sensor technology to detect these important biochemicals in the human body has the potential to significantly advance medical research for clinical applications.…”

“…[ 34 ] In human tissues, SWCNT sensors have been used in brain tissue to detect neurotransmitters. [ 35 ] In murine tissue, SWCNT sensors have been injected to detect nitric oxide, [ 36 ] miRNA, [ 31 ] chemotherapeutics, [ 11 ] and lipids. [ 30 ] Additionally, these SWCNT sensors show stability in vivo over many months suggesting their feasibility as long‐term reporters.…”

“…This can be subcategorized into error attributed to sensor movement or tissue factors. The former involves the previous cases where sensor particles are injected directly into tissues, [ 11,37,39 ] where the sensor responses can be obfuscated by emitter physical transport overtime. The latter involves the method error from factors such as breathing, heart beat, or other voluntary disturbances.…”