Polymeric micelles for neoadjuvant cancer therapy and tumor-primed optical imaging.

Poly(ethylene glycol)-block-poly(d,l-lactic acid) (PEG-b-PLA) micelles act as a 3-in-1 nanocontainer for three poorly water-soluble drugs-paclitaxel, 17-allylamino-17-demethoxygeldanamycin, and rapamycin (PTX/17-AAG/RAPA)-for cancer therapy. In a LS180 human colon xenograft model, a single intravenous (IV) injection of 3-in-1 PEG-b-PLA micelles reduced tumor volume by 1.6-fold with <10% body weight change. In a second step, IV injection of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) micelles carrying a carbocyanine dye (1,1'-dioctadecyl tetramethyl indotricarbocyanine iodide (DiR)) after 48 h resulted in a 2.1-fold higher near-infrared (NIR) optical signal from excised solid tumors versus a negative control, presumably due to a reduction in tumor cell density and interstitial tumor pressure. Thus, a tandem of 3-in-1 PEG-b-PLA and PEG-b-PCL micelles could potentially be used for neoadjuvant cancer therapy and tumor-primed NIR optical imaging for intraoperative surgical guidance in oncology, offering a promising multimodal strategy for cancer therapy and imaging.