ARTICLE
Polymeric Micelles for Neoadjuvant Cancer Therapy and Tumor-Primed Optical Imaging Hyunah Cho and Glen S. Kwon* Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, Wisconsin 53705-2222, United States
ACS Nano 2011.5:8721-8729. Downloaded from pubs.acs.org by IOWA STATE UNIV on 01/16/19. For personal use only.
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anomaterials such as quantum dots, gold nanoparticles, and nanoparticles that contain fluorescent dyes may accumulate at solid tumors through leaky vasculature, that is, the EPR effect,14 and emit fluorescence in the near-infrared (NIR) region,5,6 raising the prospect of intraoperative surgical guidance in oncology.79 While NIR optical imaging will not likely replace other imaging modalities for whole body tumor detection due to attenuation of fluorescence signals by overlying tissue, optically active nanomaterials may be used for the assessment of tumor margins, adjacent structures, and adjacent tumor deposits during surgery, supplementing visible inspection under white light and palpation.1012 It is noted that complete surgical resection is the single most important predictor of survival in patients with lung, breast, prostate, colon, and pancreatic cancers. However, nanomaterials for NIR optical imaging must fulfill central requirements in safety, targeted delivery,13,14 for example, avoidance of mononuclear phagocyte system, and molecular imaging, for example, high target-tonontarget tissue ratio.10 While nanomaterials will continue to evolve for NIR optical imaging and certainly merit more attention,15,16 strategies that overcome delivery barriers in solid tumors have drawn attention in cancer nanotechnology and may be used to improve efforts in NIR optical imaging in surgical oncology. Jain has highlighted intratumoral barriers that hinder the delivery of nanomaterials into solid tumors for therapy and imaging, noting that nanomaterials >60 nm in diameter are unable to diffuse effectively in many solid tumors.17 The distribution of blood vessels throughout solid tumors is uneven; simply, tumor regions lacking blood vessels will receive less nanomaterial than regions perfused with plenty of blood vessels.1822 Solid tumors have high interstitial fluid CHO AND KWON
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 drugspaclitaxel, 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
