Exploration Of Sol-gel Silica Based Nanomaterials For Bio-Functional Factor Delivery

The tissue damage and tumor diseases severely affect the health and life quality of human.A variety of bio-functional factors have been investigated for the treatment of diseases with the development of biomedical technology.However,inherent limitations,such as poor stability,membrane impermeability and short biological half-life of protein drug,dramatically restrict their wide applications.The poor selectivity of chemotherapy drugs reduces the efficacy of drugs and even threatens the health of patients.Therefore,exploration of novel carriers for effective drugs/functional factors delivery occupies the center part of tissue repairing and tumor therapy.The high loading efficiency,selective located at desired site,and control the release kinetics accurately are vital for effectual therapy.Mesoporous silica nanoparticles?MSNs?,with high surface area,uniform and tunable pore structure,facile surface functionalization,which make them much more accessible for application in biomedical fields.Herein,based on the characteristics above,a series of nanomaterials designed and synthesized by based on sol gel silica were explored,via a range of functional combination and surface chemical conformation,for bone tissue repair and tumor therapy.The main contents are listed as follows:1.Bioactive silica fibers with different hydrolysis degree were synthesized via a sol-gel and electrospinning approach.Due to the increased water/TEOS ratio?X ratio?,the Si-O-Si network integrity of fibers was enhanced.With a designed protein loading method using simulated body fluid?SBF?/bovine serum albumin?BSA?mixture solution,the high loading efficiency and tunable protein releasing was achieved.The varied hydrolysis degree of BG fibers was found to induce distinctive releasing behavior.The protein release kinetics intends to present a most controlled and sustained manner with the X=2.2.Photoluminescence?PL?composite fibers were synthesized by combine the CaTiO3:Yb3+,Er3+ upconversion nanoparticles?UCNPs?and bioactive silica via electrospinning method.Such nanofibers are biocompatible and can emit green and red light under 980 nm excitation.The UC PL intensity is quenched during the bone-like apatite formation on the surface of the nanofibers in simulated body fluid?SBF?;more mineral formation on the nanofibers induces more rapid optical quenching of the UC PL.Furthermore,the quenched UC PL can recover back to its original magnitude when the apatite on the nanofibers is degraded.3.A new facile approach,namely in-site sol-gel method,was successfully developed to induce the formation of fine CaF2:Yb3+,Tm3+ nanocrystals within the pore channels of mesoporous silica?mSiO₂?nanoparticles.A series of upconversion photoluminescent crystalline CaF2:Yb3+,Tm3+@mSiO₂ nanospheres with controlled diameters were fabricated by altering the volume ratio of ethanol to TEOS molecule.The nanospheres with smallest dimension?65 nm?induced the most sustained DOX release kinetics.More importantly,the in vitro study demonstrated that the DOX loaded nanospheres with smallest dimension presented the strongest anti-cancer efficacy to MCF-7 human breast cancer cells.Then the smallest nanophere was decorated with amino molecules for protein delivery.Amino-modified nanosphere presented high protein loading capacity and sustained release phenomenon.The preliminary in-vitro study confirmed markedly enhanced cell up-taking efficiency of protein macromolecules with the amino modified nanophere.4.A nanoparticle system,CaF2:Tm,Yb@ mSiO₂,made of a mesoporous silica?mSiO₂?nanosphere with CaF2:Tm,Yb upconversion nanoparticles?UCNPs?is developed,filing its mesopores and with its surface-modified with polyacrylic acid for binding the anticancer drug molecules?doxorubicin,DOX?with loading efficacy of 92%.The unique design of CaF2:Tm,Yb@mSiO₂ enables us to control the drug release by pH and 808 nm near infrared?NIR?-triggered mechanism.In addition,luminescence resonance energy transferoccurs from the UCNPs?the energy donor?to the DOX drug?the energy acceptor?in the presence of 980 nm NIR irradiation,allowing us to monitor the drug release by detecting the vanishing blue emission from the UCNPs.The in vitro study demonstrates the significantly enhanced anticancer efficiency was induced by NIR light triggered DOX release.5.A localized drug delivery device consisting of photoluminescent mesoporous silica nanoparticles?PLMSNs?and photothermal fibrous matrix was investigated.Specifically,PLMSNs modified with a pH-sensitive polydopamine?PDA?'gatekeeper'served as a doxorubicin?DOX?carrier and could release DOX once the PLMSNs were up-taken by the cancer cells.The PLMSNs were electrostatically assembled on the surface of electrospun biodegradable poly??-caprolactone?/gelatin fibrous mesh incorporated with photothermal carbon nanoparticles?CNPs?,leading to an implantable patch used as localized delivery platform.Comparing to free particulate DDSs,this implantable composite patch device was found to significantly enable superior cell up-taking effect and consequently enhance in-vitro therapeutic efficacy against tumor cells.Namely,under near infrared irradiation,the photothermal effect of CNPs in the implantable patch weakens the electrostatic interaction between the PLMSNs and poly?s-caprolactone?/gelatin/CNP fibrous mesh,resulting in the controlled release of the PLMSNs and subsequent internalization into the tumor cells for more effective cancer cell killing.