PMID- 26357961 OWN - NLM STAT- MEDLINE DCOM- 20160608 LR - 20181202 IS - 1361-6528 (Electronic) IS - 0957-4484 (Linking) VI - 26 IP - 39 DP - 2015 Oct 2 TI - One-pot synthesis of crosslinked amphiphilic polycarbonates as stable but reduction-sensitive carriers for doxorubicin delivery. PG - 395602 LID - 10.1088/0957-4484/26/39/395602 [doi] AB - In this paper, we first synthesized a novel disulfide-coupled bis-(cyclic carbonate) (TDCSS) monomer. After ring-opening co-polymerization (ROP) of TDCSS and trimethylene carbonate (TMC) initiated by mono-methoxyl poly(ethylene glycol), the crosslinked reduction-sensitive copolymer PEG-P(TMC-co-TDCSS) was obtained via a facile one-step procedure for efficient delivery of doxorubicin (DOX) into cancer cells. To serve as controls, PEG-P(TMC-co-TDCCC), which has an analogous structure without disulfide bond, and a linear polymer PEG-PTMC were also prepared. The copolymers could self-assemble to form nano-sized micelles in an aqueous solution. As compared to PEG-PTMC, crosslinked PEG-P(TMC-co-TDCSS) and PEG-P(TMC-co-TDCCC) showed lower CMC values and thus induced a much better micelle-forming ability. In vitro release studies revealed that the drug release behavior of DOX-loaded PEG-P(TMC-co-TDCSS) micelles, which could be accelerated in the presence of 10 mM dithiothreitol (DTT), showed a similar trend in the absence of DTT compared to DOX-loaded PEG-P(TMC-co-TDCCC) micelles. Furthermore, confocal laser scanning microscopy (CLSM) indicated that DOX-loaded PEG-P(TMC-co-TDCSS) micelles were efficiently internalized into HeLa cells, releasing DOX into the cytoplasm after which the drug finally entered the nuclei, while MTT assays also demonstrated potent cytotoxic activity against HeLa cells. DOX was mainly located in the cytoplasm for reduction-insensitive PEG-P(TMC-co-TDCCC) and PEG-PTMC controls. FAU - Yi, Xiaoqing AU - Yi X AD - Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072, People's Republic of China. FAU - Zhang, Quan AU - Zhang Q FAU - Dong, Hui AU - Dong H FAU - Zhao, Dan AU - Zhao D FAU - Xu, Jia-qi AU - Xu JQ FAU - Zhuo, Renxi AU - Zhuo R FAU - Li, Feng AU - Li F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150911 PL - England TA - Nanotechnology JT - Nanotechnology JID - 101241272 RN - 0 (Antibiotics, Antineoplastic) RN - 0 (Micelles) RN - 0 (Surface-Active Agents) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 80168379AG (Doxorubicin) SB - IM MH - Antibiotics, Antineoplastic/*administration & dosage/pharmacokinetics MH - Doxorubicin/*administration & dosage/pharmacokinetics MH - *Drug Delivery Systems MH - HeLa Cells MH - Humans MH - *Micelles MH - Molecular Structure MH - Nanoparticles/*chemistry/ultrastructure MH - Particle Size MH - Polyethylene Glycols/*chemistry MH - Surface-Active Agents/*chemical synthesis EDAT- 2015/09/12 06:00 MHDA- 2016/06/09 06:00 CRDT- 2015/09/12 06:00 PHST- 2015/09/12 06:00 [entrez] PHST- 2015/09/12 06:00 [pubmed] PHST- 2016/06/09 06:00 [medline] AID - 10.1088/0957-4484/26/39/395602 [doi] PST - ppublish SO - Nanotechnology. 2015 Oct 2;26(39):395602. doi: 10.1088/0957-4484/26/39/395602. Epub 2015 Sep 11.