The Penetrated Delivery of Drug and Energy to Tumors by Lipo-Graphene Nanosponges for Photolytic Therapy.
Delivery of drug and energy within responsive carriers that effectively target and accumulate in cancer cells promises to mitigate side effects and to enhance the uniquely therapeutic efficacy demanded for personalized medicine. To achieve this goal, however, these carriers, which are usually piled up at the periphery of tumors near the blood vessel, must simultaneously overcome the challenges associated with low tumor penetration and the transport of sufficient cargos to deep tumors to eradicate whole cancer cells. Here, we report a sponge-like carbon material on graphene nanosheet (graphene nanosponge)-supported lipid bilayers (lipo-GNS) that doubles as a photothermal agent and a high cargo payload platform and releases a burst of drug/energy (docetaxel (DTX) and gasified perfluorohexane (PFH)) and intense heat upon near-infrared irradiation. Ultrasmall lipo-GNS (40 nm) modified with a tumor-targeting protein that penetrates tumor spheroids through transcytosis exhibited a 200-fold increase in accumulation relative to a 270 nm variant of the lipo-GNS. Furthermore, a combination of therapeutic agents (DTX and PFH) delivered by lipo-GNS into tumors was gasified and released into tumor spheroids and successfully ruptured and suppressed xenograft tumors in 16 days without distal harm when subjected to a single 10 min near-infrared laser treatment. Moreover, no tumor recurrence was observed over 60 days post-treatment. This sophisticated lipo-GNS is an excellent delivery platform for penetrated, photoresponsive, and combined gasification/chemo-thermotherapy to facilitate tumor treatment and for use in other biological applications.
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University , Hsinchu 300, Taiwan.
Yu-Lin
YL
Su
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University , Hsinchu 300, Taiwan.
Kuan-Ting
KT
Chen
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University , Hsinchu 300, Taiwan.
Yu-Chen
YC
Sheu
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University , Hsinchu 300, Taiwan.
Shuo-Yuan
SY
Sung
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University , Hsinchu 300, Taiwan.
Ru-Siou
RS
Hsu
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University , Hsinchu 300, Taiwan.
Chi-Shiun
CS
Chiang
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University , Hsinchu 300, Taiwan.
Shang-Hsiu
SH
Hu
3D tumor model; drug delivery; graphene oxide; mesoporous structure; photoresponsive