FULL PAPER © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 4169 wileyonlinelibrary.com the vasculature, the various shapes of nanoparticles experience distinct hydrody- namic forces. Nonspherical nanoparticles readily torque and tumble, so they exhibit a stronger tendency to move towards the vessel than do spherical nanoparticles. Furthermore, spherical particles have also been documented as possessing faster macrophage internalization rates than elongated particles because spherical par- ticles travel fast towards the nucleus and exhibit hexagonal packing in the cell, compared with elongated particles that migrate slowly. [9,10] Moreover, the ability of antibody-conjugated rod-shaped particles to adhere to the target cell surface is more effective. [11] The filomicelles have also been observed to exhibit a longer circula- tion time than the spherical micelles. [12] Overall, the shape of the nanoparticles is a key factor influencing the circulation time and tumor targeting ability, which directly affect the therapeutic efficacy. 2D graphene-based materials (such as graphene oxide (GO), reduced graphene oxide (rGO) and GO-composites) exhibiting a high photoabsorbance and a large specific surface area with abundant functional groups are an excellent candidate for cargo transporting and particle decoration for drug delivery and enhanced tumor therapy. [13–15] Despite recent advancements in the drug delivery of GO, the therapeutic cargo is typically adsorbed on or tethered to the surface of GO, leading to an undesired release and other side effects. To address this issue, GO has been developed to serve as a thin shell to fully conceal large amounts of therapeutic cargo in one compact capsule. For example, GO has been deposited on a microcapsule com- posed of gold nanoparticles and poly(lactic acid) via layer-by- layer assembly and displays a high cancer killing efficacy upon NIR treatment. [16] A double emulsion of protein–graphene–pro- tein (PGP) capsule has also been made from an amphiphilic protein and rGO, to encapsulate large amounts of anticancer drugs. Applying NIR irradiation, PGP capsules widely spread anticancer drugs to eradicate tumor cells in the light-treating area, as well as the light-omitted tumor cells. [17] In addition to drug encapsulation, coating a GO layer on a gold rod also amplifies the photoacoustic property and enhanced photo- thermal stability of the gold. [18,19] Moreover, another type of Dual-Targeted Photopenetrative Delivery of Multiple Micelles/Hydrophobic Drugs by a Nanopea for Enhanced Tumor Therapy Chien-Ting Lin, I-Chieh Lin, Shou-Yuan Sung, Yu-Lin Su, Yu-Fen Huang, Chi-Shiun Chiang, and Shang-Hsiu Hu* A photoresponsive pea-like capsule (nanopea) that also represents a photo- thermal agent is constructed by wrapping multiple polymer micelles (poly- vinyl alcohol, PVA) in reduced graphene oxide nanoshells through a double emulsion approach. Resulting nanopeas can transport multiple PVA micelles containing the fully concealed hydrophobic drug docetaxel (DTX) which can be later released by a near-infrared photoactuation trigger. Through inte- grating the rod-shaped adhesion and lactoferrin (Lf ) targeting, the nanopea enhances both uptake by cancer cellc in vitro and particle accumulation at tumor in vivo. A photopenetrative delivery of micelles/DTX to the tumor site is actuated by NIR irradiation which ruptures the nanopeas as well as releases nanosized micelles/DTX. This trigger also results in thermal damage to the tumor and increases the micelles/DTX permeability, facilitating drug penetration into the deep tumor far from blood vessels for thermal chemo- therapy. This nanopea with the capability of imaging, enhanced tumor accu- mulation, NIR-triggered tumor penetration, and hyperthermia ablation for photothermal chemotherapy boosts tumor treatment and shows potential for use in other biological applications. DOI: 10.1002/adfm.201600498 Dr. C.-T. Lin, Dr. I.-C. Lin, Dr. S.-Y. Sung, Dr. Y.-L. Su, Prof. Y.-F. Huang, Prof. C.-S. Chiang, Prof. S.-H. Hu Department of Biomedical Engineering and Environmental Sciences National Tsing Hua University Hsinchu 300, Taiwan E-mail: shhu@mx.nthu.edu.tw 1. Introduction Compact nanoparticles with multiple functions are currently of considerable interest for use in biomedical applications. [1] By tuning their size and surface properties, the particles can selectively interact with specific biomolecules, which are found either in the cytoplasm or on the cell membrane, and transport cargo into the cell by crossing the plasma membrane. [2] There- fore, a variety of versatile nanoparticles with distinct organic and inorganic compositions (such as carbon-based, metallic and polymeric nanoparticles) possessing unique physicochemical features and sophisticated structures has been developed. [3–6] Remarkably, particle shape plays a significant role in biodistri- bution and cellular internalization. [7,8] While flowing through Adv. Funct. Mater. 2016, 26, 4169–4179 www.afm-journal.de www.MaterialsViews.com