Nucleobase-crosslinked poly(2-oxazoline) nanoparticles as paclitaxel carriers with enhanced stability and ultra-high drug loading capacity for breast cancer therapy  

作　　者：Si Dong Sheng Ma Hongyu Chen Zhaohui Tang Wantong Song Mingxiao Deng 

机构地区：[1]College of Chemistry,Northeast Normal University,Changchun 130024,China [2]Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China [3]University of Science and Technology of China,Hefei 230026,China [4]Jilin Biomedical Polymers Engineering Laboratory,Changchun 130022,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2022年第4期571-582,共12页亚洲药物制剂科学（英文）

基　　金：financially supported by the National Natural Science Foundation of China (51973215, 52025035, 52103194, 22105199, 51829302);Bureau of International Cooperation Chinese Academy of Science (121522KYSB20200029);the Youth Innovation Promotion Association of Chinese Academy of Sciences (2020232)

摘　　要：Poly(2-oxazoline)(POx)has been regarded as a potential candidate for drug delivery carrier to meet the challenges of nanomedicine clinical translation,due to its excellent biocompatibility and self-assembly properties.The drug loading capacity and stability of amphiphilic POxs as drug nanocarriers,however,tend to be insufficient.Herein,we report a strategy to prepare nucleobase-crosslinked POx nanoparticles(NPs)with enhanced stability and ultra-high paclitaxel(PTX)loading capacity for breast cancer therapy.An amphiphilic amine-functionalized POx(PMBEOx-NH_(2))was firstly prepared through a click reaction between cysteamines and vinyl groups in poly(2-methyl-2-oxazoline)-block-poly(2–butyl–2-oxazoline-co-2-butenyl-2-oxazoline)(PMBEOx).Complementary nucleobase-pairs adenine(A)and uracil(U)were subsequently conjugated to PMBEOx-NH2 to give functional POxs(POxA and POxU),respectively.Due to the nucleobase interactions formed between A and U,NPs formed by POxA and POxU at a molar ratio of 1:1 displayed ultrahigh PTX loading capacity(38.2%,PTX/POxA@U),excellent stability,and reduced particle size compared to the uncross-linked PTX-loaded NPs(PTX/PMBEOx).Besides the prolonged blood circulation and enhanced tumor accumulation,the smaller PTX/POxA@U NPs also have better tumor penetration ability compared with PTX/PMBEOx,thus leading to a higher tumor suppression rate in two murine breast cancer models(E0711 and 4T1).These results proved that the therapeutic effect of chemotherapeutic drugs could be improved remarkably through a reasonable optimization of nanocarriers.

关 键 词：Poly(2-oxaozoline) NANOPARTICLES PACLITAXEL Nucleobase-crosslinked Murine breast cancer 

分 类 号：R737.9[医药卫生—肿瘤]