Self-assembly And Smart Drug Release Of NIR/pH Responsive Hydroxyapatite-based Hybrid Microcapsules

In the present paper,layer-by-layer(LbL)technique was used to combine hollow hydroxyapatite(HAP),chitosan/hyaluronic acid polyelectrolyte multilayers and Au nanorods(AuNRs)to prepare remotely controllable HAP/CS/HA/AuNRs hollow hybrid microcapsules with smart responsive performance.Doxorubicin hydrochloride(DOX)was used as a model drug to investigate the drug loading and drug release properties of hybrid carriers.In this paper,the inorganic HAP was combined with natural polymers and AuNRs,which broadened the application of HAP-based intelligent drug carriers,and provided a facile and green way to fabricate remotely controlled hybrid drug carriers with high drug loading,excellent biocompatibility,and near-infrared(NIR)/pH intelligent responsiveness.This paper was divided into the following two parts.Firstly,calcium carbonate was prepared by the rapid precipitation method.HAP was synthesized by hydrothermal process subsequently using CaCO3 as template.Natural polyelectrolytes CS/HA with opposite charges were alternately deposited on the surface of HAP.After etching calcium carbonate core,DOX was loaded,and then AuNRs was electrostatically assembled on the outermost layer of HAP hybrid microcapsules to endow hybrid microcapsules with NIR responsive property.In the present paper,AuNRs was encapsulated on the outermost layer of HAP-based hybrid microcapsules acting as the "gate-keeper",endowing the hybrid microcapsules with photothermal conversion performance and NIR triggered drug release property.In vitro cytotoxicity experiments indicated that HAP/CS/HA/AuNRs had excellent compatibility.In vitro drug release experiments showed that hybrid microcapsules had high drug loading rate(85.46%)and sigjnificantly pH-/NIR-synergistic responsiveness.Secondly,based on the preparation of HAP/CS/HA/AuNRs hybrid microcapsules,HAP/CS/HA/AuNRs/GO-PEG hybrid microcapsules were prepared by introducing 4-Arm-PEG-NH2 modified graphene oxide(GO)into HAP/CS/HA/AuNRs.Compared with GO,GO-PEG displayed improved biocompatibility and stable dispersion in physiological solutions.The outer layer of AuNRs was coated with GO-PEG to prevent the excessive degradation ofAuNRs under the direct irradiation ofNIR laser.Moreover,the synergistic effect of GO-PEG and AuNRs could realize photothermal conversion,improve the photothermal conversion efficiency and photothermal stability of hybrid microcapsules.HAP/CS/HA/AuNRs/GO-PEG hybrid microcapsules displayed excellent drug loading efficiency(88.35%),and exhibited significantly enhanced NIR/pH synergistically responsiveness owing to synergistic photothermal effect of AuNRs and GO-PEG.