Nam, Jutaek La, Wan-Geun Hwang, Sekyu Ha, Yeong Su Park, Nokyoung Won, Nayoun Jung, Sungwook Bhang, Suk Ho Ma, Yoon-Ji Cho, Yong-Min Jin, Min Han, Jin Shin, Jung-Youn Wang, Eun Kyung Kim, Sang Geol Cho, So-Hye Yoo, Jeongsoo Kim, Byung-Soo Kim, Sungjee 2024-01-20T12:33:35Z 2024-01-20T12:33:35Z 2021-09-05 2013-04 1936-0851 https://pubs.kist.re.kr/handle/201004/128206 A challenge in using plasmonic nanostructure-drug conjugates for thermo-chemo combination cancer therapy lies in the huge size discrepancy; the size difference can critically differentiate their biodistributions and hamper the synergistic effect. Properly tuning the plasmonic wavelength for photothermal therapy typically results in the nanostructure size reaching similar to 100 nm. We report a new combination cancer therapy platform that consists of relatively small 10 nm pH-responsive spherical gold nanoparticles and conjugated doxorubicins. They are designed to form aggregates in mild acidic environment such as in a tumor. The aggregates serve as a photothermal agent that can selectively exploit external light by their collective plasmon modes. Simultaneously, the conjugated doxorubicins are released. The spatiotemporal concertion is confirmed at the subcellular, cellular, and organ levels. Both agents colocalize in the cell nuclei. The conjugates accumulate in cancer cells by the rapid phagocytic actions and effective blockage of exocytosis by the increased aggregate size. They also effectively accumulate in tumors up to 17 times over the control because of the enhanced permeation and retention. The conjugates exhibit a synergistic effect enhanced by nearly an order of magnitude in cellular level. The synergistic effect is demonstrated by the remarkable reductions in both the therapeutically effective drug dosage and the photothermal laser threshold. Using an animal model, effective tumor growth suppression is demonstrated. The conjugates induce apoptosis to tumors without any noticeable damage to other organs. The synergistic effect in vivo is confirmed by qRT-PCR analysis over the thermal stress and drug-induced growth arrest. English AMER CHEMICAL SOC IN-VIVO DELIVERY CELLS SIZE THERMOCHEMOTHERAPY CHEMOTHERAPY NANOSPHERES DOXORUBICIN ADRIAMYCIN TRANSPORT pH-Responsive Assembly of Gold Nanoparticles and "Spatiotemporally Concerted" Drug Release for Synergistic Cancer Therapy Article 10.1021/nn400223a 1 ACS NANO, v.7, no.4, pp.3388 - 3402 ACS NANO 7 4 3388 3402 scie scopus 000318143300053 2-s2.0-84876528747 Chemistry, Multidisciplinary Chemistry, Physical Nanoscience & Nanotechnology Materials Science, Multidisciplinary Chemistry Science & Technology - Other Topics Materials Science Article IN-VIVO DELIVERY CELLS SIZE THERMOCHEMOTHERAPY CHEMOTHERAPY NANOSPHERES DOXORUBICIN ADRIAMYCIN TRANSPORT gold nanoparticle pH-responsive drug delivery photothermal therapy synergistic effect tumor targeting