Preliminary Study Based On RGD-HBc VLPs Targeted Delivery Of Doxorubicin

BACKGROUND:Virus-like particles VLPs are more and more widely used in the field of nanodrug delivery,which has become a hot research topic in the field of targeted therapy compared with traditional drug delivery methods with the advantages of good targeting and diversity of functions.VLPs are particles assembled by viral structure proteins in a similar form to real viral particles,but without the genome structure of the virus.In many VLPs,HBV core protein virus-like particles（HBc VLPs）are widely studied because of their simple origin,easy synthesis and easy structural modification.The hollow structure inside the virus-like particles makes it capable of loading drugs and has important research value in the field of nanodrug delivery.Amycin（DOX）is a high anti-cancer activity,anti-cancer effect of a wide-spectrum anti-tumor drug,is also one of the most widely used chemotherapy drugs.For these anti-cancer drugs,strong cytotoxic effects are generally unavoidable,especially if they cause inhibition of bone marrow hematopoietic function and irreversible damage to the heart,which greatly limit the dose of DOX used for clinical cancer treatment.To date,the cardiotoxic reaction caused by DOX cannot be completely avoided.Based on the above reasons,the study of an accurate delivery of anti-tumor drugs is the key to improve the current situation of tumor treatment.Objective:To deliver tumor chemotherapy complex DOX to THE target vector of RGD-HBc VLPs,and to prepare the targeted nanocomposite RGD-HBc/DOX VLPs.In vitro cytology experiments,the tumor suppression effect and targeting of RGD-HBc/DOX VLPs targeted nanocomposites in breast cancer 4T1 cells were evaluated,in order to provide a new method for clinical tumor treatment.Methods:Using the solution self-assembly characteristic of RGD-HBc VLPs to encapsulate DOX,the target nanocomposite RGD-HBc/DOX VLPs were formed.The particle size and homogenous ity of target carrier and target nanocomposite were detected by transmission electron microscope and Malvern particle scale meter,and the biological effect of the target nanocomposite RGD-HBc/DOX VLPs was studied at the cytology level.Results:The pattern rule of the target nanocarrier RGD-HBc VLPs is good,and it is the ideal target nanocarrier.On this basis,the encapsulation DOX preparation of the anti-tumor nanocomposite RGD-HBc/DOX VLPs,through transmission electron microscope to detect its structure as a morphological rule of spherical particles;High-efficiency liquid chromatography（HPLC）detection of DOX and carrier RGD-HBc VLPs joint elution peaks confirm that DOX is loaded into the particle interior.In vitro cell experiments showed that the safety of the target vector was good,with cell survival rate of more than 80%at a concentration of 0.5 mg/m L,and RGD-HBc/DOX VLPs showed concentration dependence on the inhibition of 4T1 breast cancer cell growth.Fluorescence microscope observations show that RGD-HBc/DOX VLPs have strong target specificity to tumor cells,and competitive experiments show that RGD-HBc/DOX VLPs can interact specifically with the integratorα_vβ₃of 4T1 tumor cells.Conclusion:RGD-HBc VLPs morphological rules,uniform particle size,good stability,as a good target drug carrier,after encapsulating DOX does not affect the correct assembly and morphology of particles.Target nanocomposite RGD-HBc/DOX VLPs showed good tumor suppression and targeting at the 4T1 cell level of breast cancer.