Poly(amidoamine)(PAMAM)dendrimers are widely studied as drug vectors due to their particular structure and excellent properties.Drug molecules can be loaded in the internal cavity of dendrimers or adsorbed on the surf...Poly(amidoamine)(PAMAM)dendrimers are widely studied as drug vectors due to their particular structure and excellent properties.Drug molecules can be loaded in the internal cavity of dendrimers or adsorbed on the surface.In this paper,the interaction force and spatial configuration between PAMAM and several typical chemotherapy drugs(doxorubicin(DOX),paclitaxel(TAX),hydroxycamptothecin(HCPT))is studied by molecular dynamics(MD)simulations.Several essential parameters of dendrimers as drug carriers are analyzed by combining experiments and MD simulations,including particle size,drug loading,drug release,and biocompatibility.The simulation of dendrimer@drug complexes demonstrates that many cavities are semi-open,and most drug molecules are not completely wrapped.The internal structure of PAMAM dendrimers became looser with more extended nuclei,which increased the non-covalent interactions between PAMAM dendrimers and drug molecules.The umbrella sampling simulations reveal that the change of binding energies between dendrimers and drug molecules is responsible for the variation in drug release rate.This study provides valuable enlightenment information for the drug loading/release of PAMAM dendrimers.展开更多
Disulfide(DSF) has been proved good anti-tumor effect and even better with coadministration of Cu^(2+). In this work, we report the use of hyaluronic acid(HA) based materials to construct vectors for the delivery of b...Disulfide(DSF) has been proved good anti-tumor effect and even better with coadministration of Cu^(2+). In this work, we report the use of hyaluronic acid(HA) based materials to construct vectors for the delivery of both DSF and Cu^(2+). HA was firstly modified with polyethylene glycol monomethyl ether(mPEG) and polycaprolactone(PCL) to synthesize an amphiphilic polymer(HA-PEG-PCL). DSF could be loaded in the hydrophobic core and Cu^(2+) could be cooperated to the negative hydrophilic segment. The Cu^(2+) also played a role as crosslinking agent, which prevented DSF leakage prematurely, avoiding the bad side effects to normal tissues. The interaction between HA and CD44 improved the distribution of nanodrugs in tumor cells. When the nanodrugs were delivered to the cancer cell, the acidic micro-environment would separate the Cu^(2+) from the surface, leading to the disintegration of the micelles, promoting the release of DSF from the micelle core. The results of in vitro and in vivo experiments showed that the DSF and Cu^(2+) co-delivery vector constructed in this work could enhance the antitumor effect and have low biological toxicity.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.21874078,22074072,and 22274083)the Taishan Young Scholar Program of Shandong Province(Grant No.tsqn20161027)+5 种基金the China Postdoctoral Science Foundation(Grant No.2018M630752)the Postdoctoral Scientific Research Foundation of Qingdaothe Innovation and Development Joint Fund of Natural Science Foundation of Shandong Province(Grant No.ZR2022LZY022)the Science and Technology Planing Project of South District of Qingdao City(Grant No.2022-4-005-YY)the Exploration Project of the State Key Laboratory of Bio Fibers and EcoTextiles of Qingdao University(Grant No.TSKT202101)the High Level Discipline Project of Shandong Province。
文摘Poly(amidoamine)(PAMAM)dendrimers are widely studied as drug vectors due to their particular structure and excellent properties.Drug molecules can be loaded in the internal cavity of dendrimers or adsorbed on the surface.In this paper,the interaction force and spatial configuration between PAMAM and several typical chemotherapy drugs(doxorubicin(DOX),paclitaxel(TAX),hydroxycamptothecin(HCPT))is studied by molecular dynamics(MD)simulations.Several essential parameters of dendrimers as drug carriers are analyzed by combining experiments and MD simulations,including particle size,drug loading,drug release,and biocompatibility.The simulation of dendrimer@drug complexes demonstrates that many cavities are semi-open,and most drug molecules are not completely wrapped.The internal structure of PAMAM dendrimers became looser with more extended nuclei,which increased the non-covalent interactions between PAMAM dendrimers and drug molecules.The umbrella sampling simulations reveal that the change of binding energies between dendrimers and drug molecules is responsible for the variation in drug release rate.This study provides valuable enlightenment information for the drug loading/release of PAMAM dendrimers.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.21675091,21874078 and 22074072)the Taishan Young Scholar Program of Shandong Province(Grant No.tsqn20161027)+5 种基金the Natural Science Foundation of Shandong Province(Grant No.ZR2019BEM009)the Major Science and Technology Innovation Project of Shandong Province(Grant No.2018CXGC1407)the Key Research and Development Project of Shandong Province(Grant Nos.2016GGX102028,2016GGX102039 and 2017GGX20111)the Innovation Leader Project of Qingdao(Grant No.168325zhc)the Postdoctoral Scientific Research Foundation of Qingdao(Grant No.40518060004)the First Class Discipline Project of Shandong Province。
文摘Disulfide(DSF) has been proved good anti-tumor effect and even better with coadministration of Cu^(2+). In this work, we report the use of hyaluronic acid(HA) based materials to construct vectors for the delivery of both DSF and Cu^(2+). HA was firstly modified with polyethylene glycol monomethyl ether(mPEG) and polycaprolactone(PCL) to synthesize an amphiphilic polymer(HA-PEG-PCL). DSF could be loaded in the hydrophobic core and Cu^(2+) could be cooperated to the negative hydrophilic segment. The Cu^(2+) also played a role as crosslinking agent, which prevented DSF leakage prematurely, avoiding the bad side effects to normal tissues. The interaction between HA and CD44 improved the distribution of nanodrugs in tumor cells. When the nanodrugs were delivered to the cancer cell, the acidic micro-environment would separate the Cu^(2+) from the surface, leading to the disintegration of the micelles, promoting the release of DSF from the micelle core. The results of in vitro and in vivo experiments showed that the DSF and Cu^(2+) co-delivery vector constructed in this work could enhance the antitumor effect and have low biological toxicity.
