Construction And In Vitro And In Vivo Evaluation Of Antitumor Nanodrug Delivery System

The treatment of cancer has become an important problem to be solved all over the world.However,the existing methods of cancer treatment,including chemotherapy and radiotherapy,are generally cytotoxic.At the same time,they often bring serious toxic and side effects to normal tissues and cells.Therefore,how to transmit enough dose to the diseased tissues and reduce the toxic and side effects to normal tissues at the same time requires a specific drug delivery system.Although doxorubicin(DOX)is a widely used anticancer drug,its poor solubility,cardiotoxicity and side effects have always been a problem in its application.On the other hand,due to their unique size and surface structure,some nanoparticles can load drugs and transport them to cancer and targeted therapy.The size of nanoparticles is often smaller than that of cells and red blood cells in vivo,which provides an opportunity for the research of drug combination with nanomaterials to form new dosage forms.After loading anticancer drugs with nano materials,nano drug carriers can effectively reduce the drug particle size,increase its solubility and dissolution,improve the drug solubility and improve the therapeutic effect.In addition,the nano carrier provides a closed coating environment,so that the drug can maintain its structural integrity as far as possible before reaching the action site,effectively reduce or avoid toxic and side effects,improve the stability of the drug and maintain high biological activity.Drugs and sensors based on nanomaterial technology have been applied to practical medical applications,and can get ideal treatment and diagnosis results.In this study,we selected DOX hydrochloride with good solubility as the basic anticancer drug,and functionalized the nanomaterials with excellent performance to increase the loading capacity and targeted release function of DOX hydrochloride,so as to obtain more drug release in the weak acid environment around the tumor.It provides a new idea for the integrated modification of DOX carrier and the construction of targeted nano drug delivery system.1.Construction and in vitro evaluation of novel anticancer nanodrugs based on nano diamond loaded doxorubicin hydrochlorideAs a new type of carbon nano material,nano diamond(ND)has been widely studied and is expected to be widely used in various fields,especially in biomedical field.In this study,ester functional groups were introduced on the surface of ND by thiol click reaction.After hydrazide reaction with hydrazine hydrate,the functionalized nd based carrier materials with hydrazone bond of p H response were successfully prepared.On the other hand,the self synthesized aldehyde polyethylene glycol(CHO-PEG)and doxorubicin hydrochloride(DOX)were connected to the carrier by forming a chemical bond and hydrazone bond,which improved the water dispersibility and drug loading of the carrier.The structure,thermal stability,surface morphology and particle size of ND carrier were characterized by different equipment.The results show that we have successfully prepared these functionalized ND.The release rate of DOX in acid environment was significantly higher than that in normal physiological environment.More importantly,the results of cell viability and optical imaging show that nd based composite has good biocompatibility and therapeutic effect,and can successfully transport DOX to Hep G2 cells.In conclusion,the new ND vector constructed in this study will become a candidate for drug controlled release and tumor therapy.2.Construction and in vitro evaluation of new anticancer nanodrugs based on molybdenum disulfide loaded doxorubicin hydrochlorideMolybdenum disulfide(MoS2)is one of the most promising two-dimensional materials after graphene oxide.Because of its small size,unique two-dimensional morphology and photothermal conversion ability,it has a wide application prospect in biomedical field.However,due to the lack of special surface functional groups,their surface modification and drug loading and controlled release are hindered to a great extent.Similar to the modification method of nano diamond,the liquid phase exfoliated MoS2 sheet was used as carrier to form dynamic hydrazone bond with CHO-PEG and DOX to construct PEGylated MoS2 nano drug delivery system.The structure,thermal stability,surface morphology and particle size of MoS2 related materials were characterized by different equipment.The characterization results showed that these functionalized MoS2(MS-CO-NH)composites were successfully prepared by the formation of dynamic bonds.On the other hand,the release of MS-P-D composites loaded with CHO-PEG and DOX showed a p H responsive behavior,which had a good sustained-release effect.More importantly,the results of cell viability and internalization showed that MS-CO-NH had good biocompatibility.MS-P-D complex has a good therapeutic effect on tumor.It can transport DOX to Hep G2 cells and slowly release DOX to the nucleus to kill cancer cells.In view of these results,we believe that this new vector based on MoS2 is expected to be a candidate for controlling intracellular drug release and cancer therapy.3.Construction and in vitro and in vivo evaluation of novel nano drug based on cellulose nanocrystals loaded with adriamycin hydrochlorideBiomass material is a kind of organic polymer material which is directly extracted from renewable resources and processed by physics,chemistry and biology.In this kind of materials,cellulose nanocrystals(CNCs)are paid more and more attention due to their good crystallinity,mechanical energy,small size and relative high specific surface area.CNCs is mainly formed by further acid hydrolysis of MCC to remove the disordered part of cellulose fiber.The properties of cellulose materials have not only excellent biodegradability,biocompatibility and renewable property,but also have better mechanical properties and larger specific surface area,which undoubtedly provides a great advantage for the drug delivery field.In this study,a new strategy of surface functionalization and drug loading of nanocellulose(CNCs)and aldehyde containing polyethylene glycol(CHO-PEG)/ DOX was formed by the dehydrogenation reaction.The results showed that PEG loaded CNCs had strong DOX loading ability,DOX could be released from drug complex(P-CNCs-D),and it had p H dependence.The results of in vitro biological evaluation showed that the drug carrier(CNCs-EBONH)was negative in cytotoxic,and DOX could be transported into the cells,which had a good anti-cancer effect.Based on the research of building new nano drug based on CNCs and adriamycin hydrochloride,the new nano drugs with the best performance loaded with adriamycin hydrochloride were selected as the experimental objects for in vivo evaluation.The in vivo evaluation experiment is divided into drug distribution and in vivo efficacy experiment,and its performance is very good.Compared with other methods,the method established in this study is simple and effective,and can be used for surface functionalization and one pot loading.This work will open up a new way for the preparation of multifunctional composites based on other carbohydrate polymers or materials,and explore its application in biomedical field.