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\n Open Access Full Text Article ORIGINAL RESEARCH  \nIntegrin αvβ3 and LHRH Receptor Double Directed Nano-Analogue Effective Against Ovarian Cancer in Mice Model  \nNa Qi 1 , *, Xiantai Zhou2 , *, Ningzhu Ma2 , Jianguo Zhang2 , Zhenlin Wang2 , Xin Zhang 1 , Aimin Li 1  \n1Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, People’s Republic of China; 2Department of Pharmacy, Guilin Medical University, Guilin, 541004, People’s Republic of China  \n*These authors contributed equally to this work  \nCorrespondence: Aimin Li; Xin Zhang, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, People’s Republic of China, Email [liaimin2005@163.com](liaimin2005@163.com); [252089553@qq.com](252089553@qq.com)  \n\n| Introduction: The high mortality rate of malignant ovarian cancer is attributed to the absence of effective early diagnosis methods. The LHRH receptor is specifically overexpressed in most ovarian cancers, and the integrin αvβ3 receptor is also overexpressed on the surface of ovarian cancer cells. In this study, we designed LHRH analogues (LHRHa)/RGD co-modified paclitaxel liposomes (LHRHa-RGD-LPPTX) to target LHRH receptor-positive ovarian cancers more effectively and enhance the anti-ovarian cancer effects.\u003Cbr>Methods: LHRHa-RGD-LP-PTX liposomes were prepared using the thin film hydration method. The morphology, physicochemical properties, cellular uptake, and cell viability were assessed. Additionally, the cellular uptake mechanism of the modified liposomes was investigated using various endocytic inhibitors. The inhibitory effect of the formulations on tumor spheroids was observed under a microscope. The co-localization with lysosomes was visualized using confocal laser scanning microscopy (CLSM), and the in vivo tumor-targeting ability of the formulations was assessed using the IVIS fluorescent imaging system. Finally, the in vivo anti-tumor efficacy of the formulations was evaluated in the armpits of BALB/c nude mice.\u003Cbr>Results: The results indicated that LHRHa-RGD-LP-PTX significantly enhanced cellular uptake in A2780 cells, increased cytotoxicity, and hand a more potent inhibitory effect on tumor spheroids of A2780 cells. It also showed enhanced co-localization with endosomes or lysosome in A2780 cells, improved tumor-targeting capability, and demonstrated an enhanced anti-tumor effect in LHRHR-positive ovarian cancers.\u003Cbr>Conclusion: The designed LHRHa-RGD-LP-PTX liposomes significantly enhanced the tumor-targeting ability and therapeutic efficacy for LHRH receptor-positive ovarian cancers.\u003Cbr>Keywords: modified liposome, LHRHa, RGD, paclitaxel, ovarian cancer |\n| --- |\n| Introduction\u003Cbr>Ovarian cancer is one of the most lethal gynecological malignancies, difficult to diagnose early, and is characterized by a poor prognosis.1,2 Currently, the treatment for ovarian cancer mainly involves surgery and platinum/taxane-based chemotherapy; however, the majority of patients experience recurrence months to years after diagnosis.3,4 Generally, ovarian cancer is hormone-dependent. The expression level of the Luteinizing hormone-releasing hormone (LHRH) receptor is significantly increased in nearly 80% of human ovarian cancer cells, while its expression is minimal in most other healthy organs.5,6\u003Cbr>Physiologically, LHRH is synthesized in the hypothalamus and secreted from the pituitary.6 Natural LHRH is unstable and rapidly degraded in vivo; therefore, LHRH analogue (LHRHa) was synthesized for improved stability and bioactivity to target LHRH receptor.7 Compared to conventional protein macromolecules (LHRH), LHRHa peptides offer several advantages, including lower antigenicity, better stability, and easier preparation. Used as an active targeting |\n\nReceived: 3 October 2023  \nAccepted: 23 February 2024  \nPublishe","cbCaiigsXRZoIYrf","https://ap.wps.com/l/cbCaiigsXRZoIYrf","pdf",10282671,16,"English","# Introduction\n# Methods\n# Results\n# Conclusion","[{\"question\":\"What tumor targets do the designed liposomes address?\",\"answer\":\"The formulations are designed to target LHRH receptor-positive ovarian cancer cells and integrin αvβ3 via RGD, aiming for improved specificity.\"},{\"question\":\"How were the liposomes evaluated in the study?\",\"answer\":\"Assessments included liposome preparation and characterization, cellular uptake and viability, uptake mechanisms using endocytic inhibitors, tumor spheroid inhibition, lysosomal co-localization by CLSM, in vivo targeting by IVIS imaging, and antitumor efficacy in BALB/c nude mice.\"},{\"question\":\"What main outcomes were reported for LHRHa-RGD-LP-PTX?\",\"answer\":\"It significantly increased cellular uptake in A2780 cells, enhanced cytotoxicity, showed stronger tumor spheroid inhibition, improved co-localization with endosomes or lysosomes, and demonstrated enhanced antitumor effects in LHRH receptor-positive ovarian cancer models.\"}]","Integrin αvβ3 and LHRH Receptor Double Directed Nano-Analogue Effective Against Ovarian Cancer in Mice Model | PDF",1789988620]