As one of the major challenges in tumor chemotherapy,multidrug resistance typically correlates with the poor drug penetration within tumor tissues and drug efflux by the ATP-driven efflux pumps in tumor cells.Herein,w...As one of the major challenges in tumor chemotherapy,multidrug resistance typically correlates with the poor drug penetration within tumor tissues and drug efflux by the ATP-driven efflux pumps in tumor cells.Herein,we design a kind of near-infrared(NIR)light-and acidity-activated micellar i PUTDN nanoparticle for mitochondria-targeting doxorubicin(DOX)delivery to combat DOX resistance in small-cell lung cancer.While the PEGylated i PUTDN nanoparticles can keep stealth in blood circulation,NIR irradiation at the tumor region can peel off the PEG shell from the nanoparticles,and the exposed i RGD can facilitate deep tumor penetration of the nanoparticles.After being internalized by DOX-resistant H69AR cells,the poly(β-aminoester)s(PAE)-based nanoparticles can release the triphenylphosphonium(TPP)-conjugated DOX(TDOX)into the cytosol,which can further accumulate in mitochondria with the aid of TPP.Consequently,the mitochondrial membrane potential and ATP content are both reduced in DOX-resistant H69AR cells.The in vivo therapeutic results show that TDOX-loaded nanoparticles with the aid of NIR light irradiation can effectively suppress the DOX-resistant small-cell lung cancer without noticeable adverse effects.展开更多
基金the National Natural Science Foundation of China(Nos.11875269 and 21574136)the Beijing Natural Science Foundation(No.7212212).
文摘As one of the major challenges in tumor chemotherapy,multidrug resistance typically correlates with the poor drug penetration within tumor tissues and drug efflux by the ATP-driven efflux pumps in tumor cells.Herein,we design a kind of near-infrared(NIR)light-and acidity-activated micellar i PUTDN nanoparticle for mitochondria-targeting doxorubicin(DOX)delivery to combat DOX resistance in small-cell lung cancer.While the PEGylated i PUTDN nanoparticles can keep stealth in blood circulation,NIR irradiation at the tumor region can peel off the PEG shell from the nanoparticles,and the exposed i RGD can facilitate deep tumor penetration of the nanoparticles.After being internalized by DOX-resistant H69AR cells,the poly(β-aminoester)s(PAE)-based nanoparticles can release the triphenylphosphonium(TPP)-conjugated DOX(TDOX)into the cytosol,which can further accumulate in mitochondria with the aid of TPP.Consequently,the mitochondrial membrane potential and ATP content are both reduced in DOX-resistant H69AR cells.The in vivo therapeutic results show that TDOX-loaded nanoparticles with the aid of NIR light irradiation can effectively suppress the DOX-resistant small-cell lung cancer without noticeable adverse effects.
