Gene/Protein Disease Symptom Drug Enzyme Compound
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The development of treatment protocols that resulted in a complete response to photothermal therapy (PTT) was usually hampered by uneven heat distribution and low effectiveness. Here, we reported an NIR fluorescence and photoacoustic dual-modal imaging-guided active targeted thermal sensitive liposomes (TSLs) based on the photothermal therapy agent Indocyanine green (ICG) and antiangiogenesis agent Rapamycin (RAPA) to realize enhanced therapeutic and diagnostic functions. As expected, the in vitro drug release studies exhibited the satisfactory result of drug released from the TSLs under hyperthermia conditions induced by NIR stimulation. The in vitro cellular studies confirmed that the FA-ICG/RAPA-TSLs plus NIR laser exhibited efficient drug accumulation and cytotoxicity in tumor cells and epithelial cells. After 24 h intravenous injection of FA-ICG/RAPA-TSLs, the margins of tumor and normal tissue were accurately identified via the in vivo NIR fluorescence and photoacoustic dual-modal imaging. In addition, FA-ICG/RAPA-TSLs combined with NIR irradiation treated tumor-bearing nude mice inhibited tumor growth to a great extent and possessed much lower side effects to normal organs. All detailed evidence suggested that the theranostic TSLs which were capable of enhancing the therapeutic index might be a suitable drug delivery system for dual-modal imaging-guided therapeutic tools for diagnostics as well as the treatment of tumors.
ACS Appl Mater Interfaces 2016 Jun 08
PMID:Dual-Modal Imaging-Guided Theranostic Nanocarriers Based on Indocyanine Green and mTOR Inhibitor Rapamycin. 2718 90

Many photoresponsive dyes have been utilized as imaging and photodynamic/photothermal therapy agents. Indocyanine green (ICG) is the only near-infrared region (NIR) organic dye for clinical applications approved by the United States Food and Drug Administration; however, the clinical application of ICG is limited by its poor aqueous solubility, low cancer specificity, and low sensitivity in cancer theranostics. To overcome these issues, a multifunctional nanoplatform based on hyaluronic acid (HA) and ICG-engineered metal-organic framework MIL-100(Fe) nanoparticles (MOF@HA@ICG NPs) was successfully developed for imaging-guided, anticancer photothermal therapy (PTT). The synthesized NPs showed a high loading content of ICG (40%), strong NIR absorbance, and photostability. The in vitro and in vivo imaging showed that the MOF@HA@ICG NPs exhibited greater cellular uptake in CD44-positive MCF-7 cells and enhanced tumor accumulation in xenograft tumors due to their targeting capability, compared to MOF@ICG NPs (non-HA-targeted) and free ICG. The in vitro photothermal toxicity and in vivo PTT treatments demonstrated that MOF@HA@ICG NPs could effectively inhibit the growth of MCF-7 cells/xenograft tumors. These results suggest that MOF@HA@ICG NPs could be served as a new promising theranostic nanoplatform for improved anticancer PTT through cancer-specific and image-guided drug delivery.
ACS Appl Mater Interfaces 2017 Jan 25
PMID:Engineering Phototheranostic Nanoscale Metal-Organic Frameworks for Multimodal Imaging-Guided Cancer Therapy. 2803 5

Ideal anticancer nano drug delivery systems (NDDSs) need to overcome a series of physiological barriers including blood circulation, tumor accumulation, tumor penetration, internalization by cancer cells, lysosomal escape, and on-demand intracellular drug release following systemic administration. However, it remains a big challenge to construct NDDSs that can overcome all the barriers at the same time. Here, we develop zwitterionic temperature/redox-sensitive nanogels loaded with near-infrared (NIR) dye Indocyanine green (ICG) and anticancer drug doxorubicin (I/D@NG). I/D@NG exhibits enhanced photothermal effects, and NIR irradiation markedly decreases its diameter. NIR irradiation at tumor sites significantly enhances tumor accumulation, tumor penetration, and cellular uptake of I/D@NG with prolonged blood circulation time. Furthermore, I/D@NG can effectively escape from lysosomes by singlet oxygen-induced lysosomal disruption, and DOX is then sufficiently released from the nanogels to the nucleus in response to high intracellular GSH and photothermal effects. This nanoplatform for thermo-chemotherapy not only efficiently exerts synergistic cytotoxicity but also overcomes all the physiological barriers of therapeutic agent, thereby providing a substantial in vivo anticancer effect. The multiple functions of I/D@NG provide new insights into designing nanoplatforms for synergistic cancer therapy.
ACS Appl Mater Interfaces 2017 Jul 19
PMID:Zwitterionic Temperature/Redox-Sensitive Nanogels for Near-Infrared Light-Triggered Synergistic Thermo-Chemotherapy. 2866 11

Indocyanine green (ICG) is a fluorescent dye with a strong emission in the near-infrared spectral range that allows deep signal penetration and minimal interference of tissue autofluorescence. It has been employed in clinics for different applications, among which the more interesting is certainly near-infrared fluorescence image-guided surgery. This technique has found wide application in surgical oncology for lymph node mapping or for laparoscopic surgery. Despite ICG being useful for tracking loco-regional lymph nodes, it does not provide any information about cancer involvement of such lymph nodes or lymphatic vessels, lacking any tumor-targeting specificity. However, the clinical need in surgical oncology is not only a specific tracking of metastatic nodes but also the intraoperative detection of micrometastatic deposits. Here, we have exploited a nanotechnological solution to improve ICG usefulness by its encapsulation in H-ferritin (HFn) nanocages. They are natural protein-based nanoparticles that exhibit some very interesting features as delivery systems in oncological applications because they display specific tumor homing. We show that HFn loaded with ICG exhibits specific uptake into different cancer cell lines and is able to deliver ICG to the tumor more efficiently than the free dye in an in vivo model of TNBC. Our results pave the way for the application of ICG-loaded HFn in fluorescence image-guided surgery of cancer.
ACS Omega 2020 Jun 02
PMID:Development of Tumor-Targeted Indocyanine Green-Loaded Ferritin Nanoparticles for Intraoperative Detection of Cancers. 3254 82