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Shortwave Infrared-Emitting Theranostics for Breast Cancer Therapy Response Monitoring
Jay V Shah1, Amber Gonda1, Rahul Pemmaraju1
1Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, United States.
Abstract:
Therapeutic drug monitoring (TDM) in cancer, while imperative, has been challenging due to inter-patient variability in drug pharmacokinetics. Additionally, most pharmacokinetic monitoring is done by assessments of the drugs in plasma, which is not an accurate gauge for drug concentrations in target tumor tissue. There exists a critical need for therapy monitoring tools that can provide real-time feedback on drug efficacy at target site to enable alteration in treatment regimens early during cancer therapy. Here, we report on theranostic optical imaging probes based on shortwave infrared (SWIR)-emitting rare earth-doped nanoparticles encapsulated with human serum albumin (abbreviated as ReANCs) that have demonstrated superior surveillance capability for detecting micro-lesions at depths of 1 cm in a mouse model of breast cancer metastasis. Most notably, ReANCs previously deployed for detection of multi-organ metastases resolved bone lesions earlier than contrast-enhanced magnetic resonance imaging (MRI). We engineered tumor-targeted ReANCs carrying a therapeutic payload as a potential theranostic for evaluating drug efficacy at the tumor site. In vitro results demonstrated efficacy of ReANCs carrying doxorubicin (Dox), providing sustained release of Dox while maintaining cytotoxic effects comparable to free Dox. Significantly, in a murine model of breast cancer lung metastasis, we demonstrated the ability for therapy monitoring based on measurements of SWIR fluorescence from tumor-targeted ReANCs. These findings correlated with a reduction in lung metastatic burden as quantified via MRI-based volumetric analysis over the course of four weeks. Future studies will address the potential of this novel class of theranostics as a preclinical pharmacological screening tool.
Insights
New theranostic nanoparticles offer real-time cancer therapy monitoring. These rare earth-doped nanoparticles (ReANCs) enable early detection of metastases and assessment of drug efficacy directly at the tumor site.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Therapeutic drug monitoring (TDM) in cancer is crucial but limited by inter-patient pharmacokinetic variability.
- Plasma drug concentration assessments do not accurately reflect drug levels in tumor tissue.
- A need exists for real-time tools to monitor drug efficacy at the target site for timely treatment adjustments.
Purpose of the Study:
- To develop and evaluate novel theranostic optical imaging probes for cancer therapy monitoring.
- To engineer tumor-targeted rare earth-doped nanoparticles encapsulated with human serum albumin (ReANCs) for simultaneous imaging and drug delivery.
- To assess the capability of these ReANCs for early detection of metastases and real-time monitoring of therapeutic response.
Main Methods:
- Development of shortwave infrared (SWIR)-emitting ReANCs encapsulated with human serum albumin.
- Engineering tumor-targeted ReANCs loaded with doxorubicin (Dox) as a theranostic payload.
- Evaluation of ReANC detection capabilities in a mouse model of breast cancer metastasis, including bone lesions.
- In vitro assessment of sustained Dox release and cytotoxicity.
- In vivo therapy monitoring in a murine lung metastasis model using SWIR fluorescence measurements and MRI-based volumetric analysis.
Main Results:
- ReANCs demonstrated superior surveillance for detecting micro-lesions at 1 cm depth in a breast cancer metastasis model.
- ReANCs detected bone lesions earlier than contrast-enhanced MRI.
- In vitro studies confirmed sustained Dox release from ReANCs with comparable cytotoxicity to free Dox.
- In vivo therapy monitoring using SWIR fluorescence from tumor-targeted ReANCs correlated with reduced lung metastatic burden over four weeks, as confirmed by MRI.
Conclusions:
- Engineered ReANCs show promise as theranostic agents for evaluating drug efficacy at the tumor site.
- SWIR-emitting ReANCs enable real-time therapy monitoring and early detection of metastatic lesions.
- These novel theranostics could serve as preclinical tools for pharmacological screening and personalized cancer treatment.
