title: Polymeric micelles for neoadjuvant cancer therapy and tumor-primed optical imaging.
abstract: 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.
authors: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, Wisconsin 53705-2222, USA.
authors: Hyunah
authors: H
authors: Cho
authors: Glen S
authors: GS
authors: Kwon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D006801:Humans; D007259:Infrared Rays; D007773:Lactates / Q000737:chemistry*; D051379:Mice; D008823:Micelles; D057054:Molecular Imaging / Q000379:methods*; D050997:Nanomedicine / Q000379:methods*; D049329:Nanostructures / Q000737:chemistry; D020360:Neoadjuvant Therapy / Q000379:methods*; D055620:Optical Phenomena; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D007773:Lactates; D008823:Micelles; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols