Synergistic Inhibition Of Osteosarcoma By Polyalanine Thermo-sensitive Hydrogel In Situ Sustained-release Palbociclib And Doxorubicin

Objective: Osteosarcoma is a malignant tumor of bone that occurs in children and adolescents,with rapid deterioration and low survival rates.Existing treatments are still based on surgery and chemotherapy.Traditional chemotherapeutic drugs have large toxic side effects,poor selectivity,and are prone to drug resistance,leading to severe restrictions on their application.In recent years,immunotherapy has shown great potential in the treatment of various tumors.Therefore,the use of thermosensitive hydrogels to mount drugs with immune effects in tumors not only reduces the toxicity of normal tissues,avoids the systemic circulation of chemotherapeutic drugs,but also enables the continuous release of chemotherapeutic drugs locally,and finally achieves the inhibition of purpose.Methods: A mouse orthotopic osteosarcoma model was established by injecting mouse osteosarcoma cells(K7)into the tibial bone marrow cavity of mice(female Balb / c).Divided into four groups: Control,Gel,Doxorubicin + Pabocinib,Gel + Doxorubicin +Pabocinib.First,a polyalanine thermosensitive hydrogel was designed and synthesized,and then the drugs were injected into the tumor for treatment.The composition,infrared spectrum,phase diagram,kinetics,and morphology of polyalanine were determined.Polyalanine is loaded with drugs to measure the in vitro degradation and drug release,in vivo tumor suppression,in vivo antitumor immune effect,tumor immunogenic death,anti-pulmonary metastasis and anti-bone destruction,and survival rates Results: Compared with other groups,the Gel + Doxorubicin + Pabocinib group showed the strongest antitumor effect and antitumor immune effect,the smallest lung metastasis and bone destruction,and the longest survival rate.The difference between the groups was statistically significant(P <0.01).Conclusion: 1.The polyalanine temperature-sensitive hydrogel has suitable degradability and gelling ability,and has high biological safety.2.The hydrogel can beloaded with a drug in a liquid state,and then injected into the tumor local area of a mouse to form a hydrogel under the action of body temperature,resulting in a local precise sustained release of the chemotherapeutic drug.3.The drug-loading system produces an immune effect locally in osteosarcoma,and ultimately significantly inhibits the growth of osteosarcoma and improves the survival rate of mice.