Introduction: Nanoscale control in fabricating nanocarriers allows for multifunctional carriers that can potentially enable personalized cancer therapy that facilitates diagnosing, treating and monitoring the progress of treatment for each individual patient. Our design criterions of such a multifunctional nanocarrier for breast cancer therapy included (1) high payload of iodinated contrast agent to allow visualization using x-ray imaging, (2) capability to probe tumor vascular permeability status by detection and quantification of the intratumoral extravascular accumulation of the agent using mammography, and (3) additional payload of a chemotherapeutic for treatment.

Methods: To address this need for monitoring therapy, we developed a long-circulating 100nm-scale liposomal nanocarrier co-encapsulating an X-ray contrast agent (iodixanol) for imaging and a chemotherapeutic (doxorubicin) for treatment. We tested the nanocarrier in a rat breast tumor model developed by inoculation of mammary adenocarcinoma cells (13762 MAT BIII) into the right flank of the animals. Following systemic administration, the intratumoral, extravascular deposition of the agent was imaged with a clinical digital mammography unit while the tumor response to the treatment was evaluated by measuring the tumor growth rate and survival rate of the animals.

Results: The multifunctional nanocarrier had diameters of 105 nm and contained 140 mg/mL iodine and 3 mg/mL doxorubicin (all encapsulated). In vitro cytotoxicity studies showed that the multifunctional nanocarrier co-encapsulating doxorubicin and iodine was equally potent as the conventional liposomal doxorubicin. Following administration of the agent at a dose of 350 and 7 mg/kg body weight of iodine and doxorubicin respectively, the mammography-based imaging allowed detection and quantification of the agent's uptake by the tumor. It was observed that specific tumors that exhibited high uptake of the nanocarrier as visualized by imaging were mostly benefited from the treatment showing low tumor growth and long survival.

Conclusions: In this work, a multifunctional nanocarrier co-loaded with an imaging agent and a chemotherapeutic was developed that satisfied the design criterions. We demonstrated that the nanocarrier was capable of predicting and monitoring the therapeutic outcome of the breast cancer treatment using mammography. Such determination of the amount of chemotherapeutic reaching and remaining in the tumor during each cycle of treatment can potentially ensure an optimized personalized therapy regimen.