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Studies on polyethylene glycol-monoclonal antibody conjugates for fabrication of nanoparticles for biomedical applications. 聚乙二醇-单克隆抗体偶联物制备生物医学纳米颗粒的研究。

Journal of nanoscience and nanomedicine Pub Date : 2020-07-01 Epub Date: 2020-02-03

Funmilola Fisusi, Nailah Brandy, Jingbo Wu, Emmanuel O Akala

{"title":"Studies on polyethylene glycol-monoclonal antibody conjugates for fabrication of nanoparticles for biomedical applications.","authors":"Funmilola Fisusi, Nailah Brandy, Jingbo Wu, Emmanuel O Akala","doi":"","DOIUrl":"","url":null,"abstract":"Objective: The objective of this work is to synthesize and characterize PEGylated monoclonal antibody using the reactivity of oligosaccharide residues in the Fc region of trastuzumab and pertuzumab with a view to preserving their activities.Methods: The hydrazide-functionalized PEG monomethacrylate was synthesized and reacted with NaIO4-generated aldehyde groups on glycans in the Fc-domain of trastuzumab and pertuzumab. The conjugates were purified by HPLC. SAMSA-fluorescein substitution method and MALDI MS spectroscopy were used to determine the number of PEG per antibody. Preliminary biological studies involved antiproliferative studies and binding (flow cytometry) following treatments with SKBR3 (HER2-overexpressing) cells and the control.Results: 1H NMR and 13C NMR confirmed the formation of hydrazide-functionalized PEG monomethacrylate. MALDI mass-spectrometry showed that there are two PEGs per each antibody and it appears more reliable than the degree of SAMSA-fluorescein substitution method. HER-2 binding assay showed that PEGylated monoclonal antibody bound less efficiently to SKBR3 (high HER-2 expressing) cells than unmodified trastuzumab and pertuzumab. In vitro growth inhibitory effects of unmodified monoclonal antibodies increased with increase in concentration; while the in vitro growth inhibitory effects of PEGylated monoclonal antibodies also increased (but less than the pure antibody) with concentration and it appeared to be more active than unmodified mAbs at higher concentration.Conclusion: The results indicate that PEG can be site-specifically attached via the oxidized glycans in the Fc domain of monoclonal antibodies but the process needs further optimization in terms of PEG size and biological testing at each stage of development.","PeriodicalId":87306,"journal":{"name":"Journal of nanoscience and nanomedicine","volume":"4 2","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/96/94/nihms-1655275.PMC7869852.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25351030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cellular uptake and cytotoxicity studies of pH-responsive polymeric nanoparticles fabricated by dispersion polymerization. 通过分散聚合法制造的 pH 值响应型聚合物纳米粒子的细胞吸收和细胞毒性研究。

Journal of nanoscience and nanomedicine Pub Date : 2018-09-01 Epub Date: 2018-04-12

Reema Puri, Simeon Adesina, Emmanuel Akala

{"title":"Cellular uptake and cytotoxicity studies of pH-responsive polymeric nanoparticles fabricated by dispersion polymerization.","authors":"Reema Puri, Simeon Adesina, Emmanuel Akala","doi":"","DOIUrl":"","url":null,"abstract":"Objective: A strategy in site-specific drug delivery is the use of pH-gradients that exist in diseased conditions such as cancer for the release of loaded drug(s) in the biophase. The objective of this work is to synthesize pH-responsive docetaxel-loaded nanoparticles with a bisacrylate acetal crosslinker, which can get internalized into cells, and which will be equivalent to or more cytotoxic than the free drug against cancer cells.Methods: pH-responsive nanoparticles were synthesized by a dispersion polymerization technique. The nanoparticles were characterized for physicochemical properties. Cytotoxicity studies of the nanoparticles were performed on PC3 and LNCaP prostate cancer cell lines using a cell viability assay. Cellular uptake studies were performed using a confocal laser scanning microscope.Results: Smooth spherical nanoparticles were formed. In-vitro drug release was faster at pH 5.0 than pH 7.4, which confirmed the pH-responsiveness of the nanoparticles. Cytotoxicity studies showed that the nanoparticles were more effective at the same molar amount than the free drug against cancer cells. Both dose exposure and incubation time affected the cytotoxicity of prostate cancer cells. Furthermore, LNCaP cells appeared to be the more sensitive to docetaxel than PC3 cells. The cellular uptake studies clearly showed the presence of discrete nanoparticles within the cells in as little as 2 hours.Conclusion: pH-sensitive nanoparticles were developed; they degraded quickly in the mildly acidic environments similar to those found in endosomes and lysosomes of tumor tissues. These novel pH-sensitive nanoparticles would offer several advantages over conventional drug therapies.","PeriodicalId":87306,"journal":{"name":"Journal of nanoscience and nanomedicine","volume":"2 1","pages":"3-18"},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a0/4e/nihms-1655273.PMC8276970.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39185084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0