Construction Of Nanocarriers For Photothermal/Chemotherapy Combined Cancer Treatment And Study On Their Anti-tumor Mechanism

In recent years,great progress has been made in the construction of multifunctional nanomaterials,which can integrate multiple treatment modes into a single nanoplatform.Compared to monotherapy,the combined use of multiple therapies usually shows superior improvement in the treatment effect.Among them,chem-photothermal combined therapy has aroused great interest.This advanced combination therapy method helps obtain excellent therapeutic effects by maintaining the advantages of phototherapy(i.e.non-invasiveness,low toxicity,easy administration)and improving the problems of non-selectivity and muti-drug resistance of traditional chemotherapy.However,according to literature reports,photothermal treatment requires reaching a one-time high temperature above 50 ℃ to achieve tumor thermal ablation.Besides,cancer cells treated at low temperature(～43 °C)can quickly survive by repairing their heat shock protein HSPs.Therefore,development of a gentle PTT strategy that can achieve effective tumor ablation is particularly important for future photochemical combined cancer treatments.Built on the above considerations,to ensure low-temperature photothermalchemical combined therapy,a safe and feasible drug delivery system is highly desirable.Herein,ginsenoside Rb1-based nanovehicles were prepared through one-step coprecipitation method(DOX/Cypate/GA@Rb1)by utilizing the amphiphilicity and membrane permeability of Rb1.Encouragingly,this platform exhibited excellent biocompatibility and rapid cellular uptake.Also,the use of short-term near-infrared radiation to maintain a mild treatment temperature of 43 °C can achieves an excellent and irreversible photothermal effect.This provides an example for the construction of other low-temperature photochemical combination therapy nano-platforms for rapid drug delivery.In addition,it is very necessary for chemotherapeutic drugs to reach the pathological site smoothly and to maintain an appropriate concentration within the required time to achieve higher treatment efficiency.Therefore,we developed a nano therapeutic carrier with both endogenous and exogenous stimulus response by nanoprecipitation(DOX/Cypate@PDA-Gla).The carrier reaches the cell lysosome through cellular uptake,and PDA degrades at a slightly acidic p H.At the same time,near-infrared light irradiation can increase the temperature of the system,which weaking the force between the molecules of the Gla.The shell structure changes from dense to loose,promote the accurate and rapid release of chemotherapy drugs at the tumor site,and further combined with light-triggered hyperthermia to enhance the antitumor effect.The multifunctional design of the nano therapeutic carrier with both endogenous and exogenous stimulus responsiveness can provide a new strategy for realizing highly intelligent drug delivery in cancer treatment.