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Clinicians' Perspective in the Use and Adaptability of the Latest Methods of Diagnosis and Treatment for Cancers in Women
Published in Shazia Rashid, Ankur Saxena, Sabia Rashid, Latest Advances in Diagnosis and Treatment of Women-Associated Cancers, 2022
Gene therapy dates back to 1990, when a retroviral vector was exploited to deliver the adenosine deaminase (ADA) gene to T cells in patients with severe combined immunodeficiency (SCID). Over the years, this treatment has evolved in respect to all major cancers to minimize the off-target side effects and increase the effectiveness to specific genes. Folate receptor is a membrane-bound protein which mediates folate uptake by endocytosis, essential for DNA synthesis, cell division and growth, which adds an advantage during malignancy. This was targeted with the development of the folate receptor targeting nano-liposomes to deliver a pigment epithelium-derived factor (PEDF) gene to HeLa cells showing high transfection efficiency and effective anti-tumour activity. This forms the basis that there are multiple ways to target malignancy, especially based on molecules that express themselves on their surface [15].
Antimetabolites
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
This principle was made use of by AstraZeneca in designing plevitrexed (ZD-9331), which is efficiently transported into cells via the RFC mechanism and reached Phase II clinical trials for the treatment of gastric cancer. However, it is not a substrate for FPGS and is not polyglutamated, so it is unaffected by resistance due to down regulation of this enzyme. However, it is taken up by the α-isoform of the folate receptor (αFR). Folate receptors are high-affinity folate-binding membrane glycoproteins, which some cells, such as ovarian tumor cells, overexpress.
Precision medicine in ovarian carcinoma
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
Shailendra Dwivedi, Purvi Purohit, Radhieka Misra, Jeewan Ram Vishnoi, Apul Goel, Puneet Pareek, Sanjay Khattri, Praveen Sharma, Sanjeev Misra, Kamlesh Kumar Pant
Folate is an essential component required by rapidly dividing cells since it is important for DNA synthesis and helps promote cell division. Targeting folate and folate receptors can prove to be potentially useful in tumor growth regression. The folate dependent drugs can be categorized as Folate antagonistsFolate receptor inhibitorsFolate-conjugated therapeutic agents
Development of tumor-specific liposomes containing quantum dots-photosensitizer conjugate used for radiotherapy
Published in Journal of Liposome Research, 2022
M. Karabuga, S. Erdogan, S. S. Timur, I. Vural, S. Çalamak, K. Ulubayram
So far, studies on QDs-photosensitizer conjugate were focused on the synthesis of the conjugate and its radiosensitizer effect. It is well known that designed to accumulate in tumors via passive and active targeting strategies, these conjugates may selectively enhance the effect of X-rays in tumor cells. For this purpose, passively and/or actively targeted drug delivery systems such as liposomes are used. Therapeutic molecules loaded liposomes can be targeted to specific parts of the body where there is solely diseased tissue, thereby avoiding interaction with healthy tissue and preventing any damage to the healthy tissue via the drug. For active targeting different types of ligands have been used so far. The folate receptor is a tumor-associated antigen that can bind with folate and its conjugates with high affinity and ingests the bound molecules inside the cell via the endocytic mechanism. Folic acid is used as a targeting ligand for the delivery of a wide variety of payloads to different types of cancer cells including breast, ovarian, lung, and colon cancers which are overexpressed folate receptors (Kumar et al.2019).
Recent progress in therapeutic strategies and biomimetic nanomedicines for rheumatoid arthritis treatment
Published in Expert Opinion on Drug Delivery, 2022
Chunhong Li, Xiu Zheng, Mei Hu, Ming Jia, Rongrong Jin, Yu Nie
To improve drug delivery and control drug release in inflamed arthritic tissues, active targeting NPs sensitive to environmental stimuli, such as pH, enzymes, and hypoxia have emerged [87,88]. Multifunctional folate receptor-targeting and pH-responsive nanocarriers that were developed for the targeted delivery of methotrexate were taken up by activated macrophages to a greater extent than unmodified NPs, and they were more cytotoxic to the macrophages. The therapeutic effect of these NPs in RA was confirmed in rats with adjuvant-induced arthritis [75]. Enzyme-responsive NPs loaded with celastrol and modified with the arginine-glycine-aspartic acid (RGD) peptide, which binds αvβ3 integrin, enhanced the therapeutic efficacy of celastrol by promoting the apoptosis of activated macrophages and osteoclasts in RA joints [30,41]. Those NPs effectively mitigated joint inflammation and bone destruction in vivo.
Conjugates of TAT and folate with DOX-loaded chitosan micelles offer effective intracellular delivery ability
Published in Pharmaceutical Development and Technology, 2019
Shengyu Zhang, Yanjun Liu, Ye Gan, Nanqing Qiu, Yueqing Gu, Hongyan Zhu
In many previous studies, various ligands or moieties targeting specific receptors of tumor cells have been used to modify the surface of polymeric micelles for improving the curative effects and minimizing the side effects of chemotherapeutics. Among them, folate has been widely used as a targeting ligand owing to the high affinity between folate (FA) and folate receptor (FR) (Qin et al. 2013; Zhang et al. 2014). In this study, we utilized this characteristic of folate to achieve the target ability of micelles. But, we worried about that the cargo is entrapped in intracellular vesicles and cannot exert its biological activity because of folate-mediated endocytosis pathway. So, we designed the TAT and folate dual-modified PEG-OC micelles (folate/TAT-PEG-OC). We hope that with the help of TAT peptide, the micelles can penetrate the cell membrane by electrostatic interactions which can avoid the limitation which was mentioned above. Under such a design, chitosan was used as skeleton, PEG and octyl group, respectively, provide hydrophobic and hydrophilic structures, folate and TAT peptide endow the micelles with the ability of targeting tumor cells with high folate receptor expression and the enhanced intracellular uptake capacity.