Currently, photodynamic therapy (PDT) of primary tumors in peritoneal organs is limited by the lack of specificity of photosensitizers (PSs) and availability of appropriate laparoscopy for accurate and dexterous PDT optical fiber deployment. Invasive procedures are often required in the conventional approach, leads to significant side effects such as bleeding and extended recovery time. The purpose of this study is to design and evaluate a soft robot system for targeted and minimally invasive PDT of intraperitoneal tumors. Our soft robot system is fabricated with silicone materials to enable safe interaction with the abdominal organs. Compared to the conventional laparoscopic device, this soft robot system can be translated, bent, and rotated to reach the desired target by using three high-resolution DC motors. A miniature camera (ENA-10005-AS, Enable Inc.) is integrated with the soft robot to enable the intraoperative image guidance while reaching the target. A hollow channel was created within the soft robot so as to deploy the optical fiber towards the tumor. We conducted interstitial PDT using a peritoneal ovarian tumor mouse model and targeted near infrared photosensitizer. After the PS was injected, the optical fiber was inserted into the tumors through the soft robot. We found that PDT treatment greatly inhibited tumor growth. Our preliminary results suggest that our soft robot system may have great potential in the PDT treatment of intraperitoneal tumors.
Chemoresistance is a significant challenge in the treatment of patients with ovarian cancer. An important mechanism in resistance to cisplatin is increased drug efflux from tumor cells, potentially mediated by ATPdependent factors such as the ATPases, ATP7A/ATP7B, and the ATP binding cassette (ABC) family member, MRP2. Therefore, a promising strategy to overcome chemoresistance is targeted inhibition of ATP production in tumor cells. In this work, we developed a mitochondria-targeted photodynamic therapy (PDT) approach in ovarian tumors to overcome chemoresistance.
Cannabinoids are emerging as promising antitumor drugs. However, complete tumor eradication solely by cannabinoid therapy remains challenging. In this study, we developed a far-red light activatable cannabinoid prodrug, which allows for tumor-specific and combinatory cannabinoid and photodynamic therapy. This prodrug consists of a phthalocyanine photosensitizer (PS), reactive oxygen species (ROS)-sensitive linker, and cannabinoid. It targets the type-2 cannabinoid receptor (CB2R) overexpressed in various types of cancers. Upon the 690-nm light irradiation, the PS produces cytotoxic ROS, which simultaneously cleaves the ROS-sensitive linker and subsequently releases the cannabinoid drug. We found that this unique multifunctional prodrug design offered dramatically improved therapeutic efficacy, and therefore provided a new strategy for targeted, controlled, and effective antitumor cannabinoid therapy.
Cannabinoid CB2 receptors (CB2R) hold promise as therapeutic targets for treating diverse diseases, such as cancers, neurodegenerative diseases, pain, inflammation, osteoporosis, psychiatric disorders, addiction, and immune disorders. However, the fundamental role of CB2R in the regulation of diseases remains unclear, largely due to a lack of reliable imaging tools for the receptors. The goal of this study was to develop a CB2R-targeted molecular imaging probe and evaluate the specificity of the probe using human tumor cells that naturally overexpress CB2R. To synthesize the CB2R-targeted probe (NIR760-Q), a conjugable CB2R ligand based on the quinolone structure was first prepared, followed by bioconjugation with a near-infrared (NIR) fluorescent dye, NIR760. In vitro fluorescence imaging and competitive binding studies showed higher uptake of NIR760-Q than free NIR760 dye in Jurkat human acute T-lymphoblastic leukemia cells. In addition, the high uptake of NIR760-Q was significantly inhibited by the blocking agent, 4-quinolone-3-carboxamide, indicating specific binding of NIR760-Q to the target receptors. These results indicate that the NIR760-Q has potential in diagnostic imaging of CB2R positive cancers and elucidating the role of CB2R in the regulation of disease progression.
KEYWORDS: Luminescence, Tumors, Near infrared, Digital breast tomosynthesis, Receptors, Imaging systems, Absorption, In vitro testing, In vivo imaging, Liver
Recent studies indicate that the type 2 cannabinoid receptors (CB 2 R ) have become an attractive target for treating a variety of pathologies, including cancers, neurodegenerative diseases, inflammation, pain, osteoporosis, immunological disorders and drug abuse. In addition, it appears that many of these diseases have up-regulated CB 2 R expression. However, the precise role of CB 2 R in the regulation of diseases remains unclear. The ability to specifically image CB 2 R would contribute to develop reliable CB 2 R -based therapeutic approaches with a better understanding of the mechanism of CB 2 R action in these diseases. We developed a CB 2 R -targeted zwitterionic near-infrared (NIR) fluorescent probe, ZW760-mbc94. When compared with a previously reported CB 2 R probe (NIR760-mbc94) with the same targeting moiety but a charged NIR fluorescent dye, ZW760-mbc94 showed improved binding specificity in vitro and ex vivo. Overall, ZW760-mbc94 appears to have great potential as a CB 2 R -targeted contrast agent.
Intervertebral disc degeneration (IDD) is closely associated with low back pain. Typically nonsurgical treatment of IDD is the most effective when detected early. As such, establishing reliable imaging methods for the early diagnosis of disc degeneration is critical. The cellular and tissue localization of a facile functional fluorescent probe, HYK52, that labels disc annulus fibrosus is reported. HYK52 was synthesized with high yield and purity via a two-step chemical reaction. Rabbit disc cell studies and ex vivo tissue staining images indicated intracellular localization and intervertebral disc (IVD) tissue binding of HYK52 with negligible cytotoxicity. Moreover, HYK52 is purposefully designed with a functional terminal carboxyl group to allow for coupling with various signaling molecules for multimodal imaging applications. These results suggest that this IVD-targeted probe may have great potential in early diagnosis of IDD.
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