pH‑responsive nanosystems based on reduced graphene oxide grafted with polycaprolactone‑block‑poly(succinyloxyethylmethacrylate) for doxorubicin release

pH‑responsive nanosystems based on reduced graphene oxide grafted with polycaprolactone‑block‑poly(succinyloxyethylmethacrylate) for doxorubicin release

Bakhshali Massoumi1 · Raana Sarvari2 · Leila Khanizadeh1 · Samira Agbolaghi3 · Younes Beygi‑Khosrowshahi3

 

Abstract
pH-responsive nanocarriers were synthesized via polycaprolactone-b poly(succinyloxyethylmethacrylate) copolymers grafted onto reduced graphene oxide (rGO-g-PCL-b-PSEMA) for anticancer drug delivery applications. For this propose, ε caprolactone monomer was polymerized from –OH groups of rGO with ring-opening polymerization (ROP) to obtain polycaprolactone grafts (rGO-g-PCL). In the next step, 2 hydroxyethylmethacrylate monomer was polymerized from PCL end through atom transfer radical polymerization to afford rGO-g-PCL-b-poly(hydroxyethylmethacrylate) (PHEMA). The pH-responsive rGO-g-PCL-b-PSEMA was obtained by reacting rGO-g-PCL-b-PHEMA with excess succinic anhydride in pyridine under mild conditions. The pH sensitivity of nanosystems was confirmed via dynamic light scattering at pH values of 4 and 7.4. Doxorubicin encapsulation efficacy was calculated to be 92%. The effect of pH on release behaviors of rGOg- PCL-b-PSEMA nanocarriers was investigated. Therelease rates at pH values of 7.4, 5.4 and 4 were about 52.1, 64.2 and 68.63 wt% after 775 min and at 37 °C. The release rate was improved at tumor simulatedenvironment (42 °C and pH ≤ ۵٫۴).The cytotoxic effects of nanosystems were appraised by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the results indicated that novel smart nanosystems were nontoxic to MCF-7 cells and can be applied as anticancer drug deliver

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Intravenous immunoglobulin (IVIG) treatment modulates peripheral blood Th17 and regulatory T cells in recurrent miscarriage patients: Non randomized, open-label clinical trial

Intravenous immunoglobulin (IVIG) treatment modulates peripheral blood Th17 and regulatory T cells in recurrent miscarriage patients: Non randomized, open-label clinical trial

Majid Ahmadia,b,c,d, Sanaz Abbaspour aghdamd, Mohammad Nouria,e, Zohreh Babalood, Laya Farzadie, Aliye Ghasemzadehe, Kobra Hamdie, Ali Akbar Movassaghpourf,Farhad Jadidi-Niaraghb,d, Amir Afkhamd, Morteza Motallebnezhada,b, Shadi Eghbal-Fardd ,Sanam Dolatib,d, Vahid Younesig, Mehdi Yousefib,d,

a Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
b Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
c Student’s Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran d Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
e Reproductive Biology Department, Tabriz University of Medical Sciences, Tabriz, Iran

f Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
g Pishtaz Teb Diagnostics, Tehran, Iran

ABSTRACT

Background: Th17 cells and Treg cells have been proposed as new risk factors for recurrent miscarriage (RM). In this study, we investigated the effect of Intravenous immunoglobulin G (IVIG) on the levels and function of Th17 and Treg cells and pregnancy outcome in women with RM. Materials and methods: 94 pregnant women with RM were enrolled in this study. Blood was drawn at the time of positive pregnancy. On the same day, IVIG 400 mg/kg was administered intravenously for 44 patients. 50 other RM patients were included as no IVIG interfering control group. Following the first administration, IVIG was given every 4 weeks through 32 weeks of gestation. Peripheral blood was drawn after the last administration (32 weeks after pregnancy). Results: IVIG down-regulated Th17 cells population and function and up-regulated Treg cells population and function were significant in the treated group. Pregnancy outcome in IVIG treated subjects was successful in 38 out of 44 RM women (86.3%). However, pregnancy outcome was successful in 21 out of 50 untreated RM women (42%). Conclusion: Administration of IVIG in RM women with cellular immune cells abnormalities during pregnancy influences Th17/Treg ratio in peripheral blood and enhances Treg and decreases Th17 responses.

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