Osteoporosis is a disease of bone metabolism homeostasis imbalance with obvious bone loss,damage to bone microstructure,and increased risk of fracture.The occurrence and development of osteoporosis is related to the a...Osteoporosis is a disease of bone metabolism homeostasis imbalance with obvious bone loss,damage to bone microstructure,and increased risk of fracture.The occurrence and development of osteoporosis is related to the augmentation of active osteoclasts.Receptor activator of nuclear factor kappa B(RANK)small interfering RNA(siRNA)knockdowns the expression of RANK mRNA to inhibit the osteoclast precursors differentiate into osteoclasts as a treatment in osteoporosis.Salmon calcitonin(sCT)is a commonly used anti-osteoporotic agent that inhibits osteoclast activity and induces osteoclast apoptosis,and it also could promote the osteogenesis by osteoblasts.A cocktail therapy improves the therapeutic effect of osteoporosis between RANK siRNA and sCT.A size-switchable microsphere from micro to nano scale was developed to address the delivery barriers of biomacromolecules with poor stability and frequent administration.RANK siRNA and s CT were incorporated into the microspheres with a nanoparticle/micellemicrosphere double-layer structure to achieve sustained release when the particle size shrunk and dual protection of RANK siRNA and sCT.The size-switchable microspheres MS@(AL-NPs/ARM)had an optimal therapeutic effect and reduced the frequency of administration in glucocorticoid induced osteoporosis(GIOP)mouse model.RANK siRNA and s CT co-delivery system based on size-switchable microsphere is a promising strategy to treat osteoporosis through the controlled release of biomacromolecules.展开更多
Size is one of the most important characteristics of nanoparticles to influence their biodistribution and antitumoral efficacy.Particles with large sizes have difficulty in deep tumor penetration,while small particles...Size is one of the most important characteristics of nanoparticles to influence their biodistribution and antitumoral efficacy.Particles with large sizes have difficulty in deep tumor penetration,while small particles are easily removed from tumor tissues due to the high tumor interstitial fluid pressure.To address these issues,an intelligent core-crosslinked polyion complex micelle(cPCM)with a reversibly sizeswitchable feature was engineered in this study.The micelles are consisting of methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PLA),mPEG-PLA-(HE)6CC,and mPEG-PLA-(RG)6CC at an optimal mass ratio of 6:1:1 with an antiangiogenic compound,dabigatran etexilate(DE),encapsulated.The net charge inside the micelles is switchable when exposed to different pH conditions,thereby leading to revisable size-change of micelles.DE-loaded micelles(DE@cPCM)can swell and release drugs at the tumor sites with a mildly acidic pH,while they shrink and protect the cargo from leaking into the blood circulation with a neutral pH.Results indicated that DE@cPCM can inhibit tumor angiogenesis in vitro and in vivo,thereby efficiently restraining tumor growth in a 4T1-bearing mouse model.Collectively,the sizeswitchable cPCM is a promising nanoplatform for targeting delivery of anticarcinogens into the matrix of tumor tissues.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82003687,52203138)supported by the Jilin Scientific and Technological Development Program(No.20200201415JC)+1 种基金supported by the Finance Project of Jilin ProvinceChina(Nos.2019SRCJ016,2020SCZT036)。
文摘Osteoporosis is a disease of bone metabolism homeostasis imbalance with obvious bone loss,damage to bone microstructure,and increased risk of fracture.The occurrence and development of osteoporosis is related to the augmentation of active osteoclasts.Receptor activator of nuclear factor kappa B(RANK)small interfering RNA(siRNA)knockdowns the expression of RANK mRNA to inhibit the osteoclast precursors differentiate into osteoclasts as a treatment in osteoporosis.Salmon calcitonin(sCT)is a commonly used anti-osteoporotic agent that inhibits osteoclast activity and induces osteoclast apoptosis,and it also could promote the osteogenesis by osteoblasts.A cocktail therapy improves the therapeutic effect of osteoporosis between RANK siRNA and sCT.A size-switchable microsphere from micro to nano scale was developed to address the delivery barriers of biomacromolecules with poor stability and frequent administration.RANK siRNA and s CT were incorporated into the microspheres with a nanoparticle/micellemicrosphere double-layer structure to achieve sustained release when the particle size shrunk and dual protection of RANK siRNA and sCT.The size-switchable microspheres MS@(AL-NPs/ARM)had an optimal therapeutic effect and reduced the frequency of administration in glucocorticoid induced osteoporosis(GIOP)mouse model.RANK siRNA and s CT co-delivery system based on size-switchable microsphere is a promising strategy to treat osteoporosis through the controlled release of biomacromolecules.
基金supported by the National Natural Science Foundation of China(Nos.81972894,22278442,82273882)。
文摘Size is one of the most important characteristics of nanoparticles to influence their biodistribution and antitumoral efficacy.Particles with large sizes have difficulty in deep tumor penetration,while small particles are easily removed from tumor tissues due to the high tumor interstitial fluid pressure.To address these issues,an intelligent core-crosslinked polyion complex micelle(cPCM)with a reversibly sizeswitchable feature was engineered in this study.The micelles are consisting of methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PLA),mPEG-PLA-(HE)6CC,and mPEG-PLA-(RG)6CC at an optimal mass ratio of 6:1:1 with an antiangiogenic compound,dabigatran etexilate(DE),encapsulated.The net charge inside the micelles is switchable when exposed to different pH conditions,thereby leading to revisable size-change of micelles.DE-loaded micelles(DE@cPCM)can swell and release drugs at the tumor sites with a mildly acidic pH,while they shrink and protect the cargo from leaking into the blood circulation with a neutral pH.Results indicated that DE@cPCM can inhibit tumor angiogenesis in vitro and in vivo,thereby efficiently restraining tumor growth in a 4T1-bearing mouse model.Collectively,the sizeswitchable cPCM is a promising nanoplatform for targeting delivery of anticarcinogens into the matrix of tumor tissues.
