Study On The Preparation And Properties Of Gold Nanorods@mesoporous Silica Composite Nanoparticles Active Targeting Drug Delivery System

Cancer treatment is a complex process,however,a ideal treatment outcome is not achieved by chemotherapy alone.Compared with chemotherapy alone,the combination of photothermal therapy and chemotherapy could enhance anticancer efficacy.Compared to the single-targeted drug delivery system,the multi-targeted drug delivery system has a great potential to enhance selectivity and targeting for cancer cells.Therefore,a nanocarrier?GNRs@mSiO₂-HA-RGD?was developed by conjugating targeting ligand hyaluronic acid?HA?and RGD with mesoporous silica-coated gold nanorods?GNRs@mSiO₂?for dual-targeted chemo-photothermal therapy.DOX?Doxorubicin hydrochloride?,which is a broad-spectrum anticancer drug and easily cause side effects,was loaded into?GNRs@mSiO₂-HA-RGD?nanocarrier that not only overcome the clinical drawbacks of DOX but also exhibit dual-targeted chemo-photothermal therapy.Firstly,GNRs were conducted by the seed-mediated method.GNRs@mSiO₂nanoparticles with core-shell,well-proven photothermal nano material,were achieved by the modified St?ber method.The TEM showed that the a verage length and width of GNRs were 45±4 nm and 10±2 nm,respectively,and mesoporous silica shells of thickness was about 10 nm.GNRs@mSiO₂ nanoparticles were extracted with NH₄NO₃/methanol to remove the CTAB residual in the mesoporous channels.Then,GNRs@mSiO₂ nanoparticles were functionalized with amino by a post-grafting method to obtain GNRs@mSiO₂-NH₂.Secondly,the CGRGDSY peptide was introduced as a side chain of hyaluronic acid by performing a Michael-type addition of the cysteine-containing CGRGDSY peptide onto HA that was previously functionalized with methacrylamide groups,therefore,a dual-target molecules?HA-RGD?was obtained.Then,the dual-targeted GNRs@mSiO₂-HA-RGD nanocarrier was synthesized by coupling GNRs@mSiO₂with HA-RGD through the EDC-mediated amidation reaction.The photothermal responsive behavior of nanoparticles demonstrated that GNRs@mSiO₂-HA-RGD nanoparticles have excellent photothermal conversion effect.DOX was readily loaded into the GNRs@mSiO₂-HA-RGD through electrostatic interactions with 20.16%loading capacity.The drug release study showed DOX-GNRs@mSiO₂-HA-RGD was pH-enzyme sensitive drug release manner and NIR laser irradiation could increase the release of DOX.Finally,cytotoxicity and cellular uptake of different nanoparticles were investigsted.These findings indicated that the DOX-GNRs@mSiO₂-HA-RGD had a higher cytotoxicity to tumor cells and a lower cytotoxicity to normal cells.Compared with chemotherapy or photothermal therapy alone,significantly increased cell killing has also been found in SKOV-3 cells incubated with DOX-GNRs@mSiO₂-HA-RGD under NIR irradiation,realizing a synergistic effect.Cellular uptake studies indicated that DOX-GNRs@mSiO₂-HA-RGD drug delivery system exhibited excellent tumor-targeting performance via CD44 and integrin receptors mediated endocytosis.A competitive inhibition experiment further confirmed that the uptake of DOX-GNRs@mSiO₂-HA-RGD was a dual-receptor mediated process.Overall,the drug delivery system?DOX-GNRs@mSiO₂-HA-RGD?could double target for tumor cells and realized the combined chemotherapy and photothermal therapy,which indicated a promising system for cancer treatment.