Construction Of Nano Calcium Carbonate Drug Delivery System For Tumor Precision Therapy

The rapid development of nanotechnology provides a new strategy for the precise treatment of tumors.Therefore,it is possible to use the features of the microenvironment of the cancer site to construct and synthesize targeted drugs with excellent biocompatibility to reach the purpose of precise tumor treatment.In this thesis,based on the slightly acidic tumors,two nano-calcium carbonate drug delivery systems were constructed to solve the problems of large dosage of a single treatment method and low therapeutic efficiency.The constructed nano-calcium carbonate drug-carrying system has excellent therapeutic effects and good biocompatibility with low toxicity and side effects.The designed nano drug delivery system was verified through three aspects:in vitro material characterization,cellular level experiment and in vivo animal treatment experiment.The principal research contents and results are as follows:1.Acid response nano-calcium carbonate loaded with doxorubicin and protoporphyrin for tumor chemical and photodynamic combined therapySingle treatment methods such as chemotherapy and photodynamic therapy have been verified to have good tumor treatment effects,but there are still certain disadvantages.It is more complicated to treat with monotherapy alone,and it can cause damage to normal parts of the human body when the dosage is large.At the same time,small molecule drugs will lose too much due to normal metabolism in the process of drug delivery to target tumor sites.As an inorganic carrier,calcium carbonate nanoparticles are simple to synthesize,and therapeutic drugs can be loaded into them with high efficiency.Here,the acid-responsive CaCO₃@PD nanoparticles loaded with both doxorubicin and protoporphyrin were designed.Due to the excellent acid responsiveness of calcium carbonate,it can precisely target the tumor site while releasing DOX and Pp IX drugs.Doxorubicin is a traditional broad-spectrum chemotherapeutic drug,which has been proven to have a good anti-cancer effect.As a traditional photosensitizer,protoporphyrin can achieve the purpose of apoptosis through photodynamic action.Therefore,the purpose of combined treatment of chemotherapy and photodynamic therapy is achieved.Combination therapy effectively improves the therapy consequent of a single treatment method,improves the therapy efficiency.Under slightly acidic conditions,cell survival rate is less than 20%,and solves the problem of harm to normal physiological tissues caused by excessive dosage of a single drug and lighting time.Meanwhile,calcium carbonate nanomaterials are non-toxic and highly safe,and the nanoparticles formed by encapsulating two drugs have good biocompatibility,will not cause damage to normal tissues,and have good biological advantages.2.Acid response nano-calcium carbonate loaded with capsaicin to specifically open TRPV1 channel for tumor calcium ion therapyCapsaicin is a natural non-toxic small molecule organic substance,which is often used clinically to relieve inflammation and pain.As an inorganic material,calcium carbonate nanoparticles have a simple synthesis method,and therapeutic drugs can be easily wrapped in them.Here,we report the acid-responsive CaCO₃@CAP nanoparticles loaded with capsaicin,which can specifically activate TRPV1 channels and trigger tumor calcium ion therapy.In order to improve the stability and dispersibility of calcium carbonate nanoparticles in aqueous solution,the outer layer was modified with a PEGylated phospholipid bilayer,so that the nanoparticles could maintain a stable and dispersed spherical shape in the aqueous solution.And the excellent acid responsiveness of calcium carbonate enabled it to precisely target the tumor site.The released capsaicin could specifically activate the TRPV1 channel,overloaded the intracellular calcium ion concentration and caused cell apoptosis.Making the cell survival rate under slightly acidic conditions less than 25%and providing a safer and cheaper new way for treatment.We proved that the naturalness and non-toxicity of capsaicin and calcium carbonate nanoparticles make the CaCO₃@CAP nanoparticles have excellent biocompatibility,which has good development prospects and clinical application potential.