Construction And Performance Study Of A Novel Nano-delivery System For Drug-resistant Colon Cancer

Colon cancer(CRC)is one of the cancer types with the highest incidence,and chemotherapy is still the main treatment for patients with advanced CRC.Fusobacterium nucleatum(Fn)existed in the CRC tissue can reduce the concentration of anti-cancer drugs in the tumor,and thus leads to CRC resistance to oxaliplatin(OXA)and other chemotherapy drugs.At the same time,Fn is also easy to form a bacterial biofilm related to the production of CRC.The formation of biofilm not only promotes the adhesion and growth of bacteria,but also reduces the bacteria’s sensitivity to radiation and anti-cancer drugs,increasing the difficulty of treatment.Therefore,if chemotherapeutic drugs are used to treat colon cancer while killing Fn and dispersing the bacterial biofilm,the resistance of colon cancer to chemotherapeutic drugs can be reduced.Based on this,we designed a strategy to reduce the resistance of CRC to OXA by combining the antibacterial substance lauric acid(LA)to kill Fn.This strategy introduces LA and OXA into branched polyethyleneimine(PEI)through amidation reaction,and forms PEI-LA-Pt nanomicelles through self-assembly.Then,HA was coated on the surface of the nanomicelles through electrostatic interaction to prepare PEI-LA-Pt@HA nanomicelles.Dynamic light scattering(DLS)and scanning electron microscopy(SEM)measurements show that PEI-LA-Pt@HA nanomicelles are spherical structures with a diameter of about 200 nm,which can be enriched in the tumor site through enhanced penetration and retention effects.It was verified by ICP-MS that the nanomicelles had a higher drug loading,a higher cellular uptake rate,and a reduction stimulation response under glutathione conditions.The plate counting method proved that the nanomicelles have a good inhibitory effect on Fn.Observations by crystal violet staining and confocal imaging show that nanomicelles can effectively disperse biofilms.In vitro cytotoxicity results show that nanomicelles are low in toxicity to normal cells and highly toxic to colon cancer cells,and the cytotoxicity of Fn and HT29 cells co-cultured proves that nanomicelles can solve the problem of CRC drug resistance.This strategy of combining antibacterial molecules and chemotherapy to reduce the drug resistance of cancer cells has great potential and application value.