Initiated by the interaction between AP2H and membrane-anchored LAPTM4B protein, PDC specifically recognized and bound cancer cells. The receptor-mediated endocytic pathway then led to the delivery of PDC to lysosomes. The low pH environment in lysosomes efficiently cut the hydrazone bond and released TPP-DOX. The successful escape from lysosomes enabled further transportation of TPP-DOX to mitochondria directed by targeting group TPP. Because TPP-DOX is highly active in producing ROS and mitochondria are prone to oxidative damage, the disruption in the electron transport chain and ATP synthesis finally lead to mitochondrial dysfunction and cell death. With dual-targeting ability, PDC can effectively bypass the interaction with P-gp. Meanwhile, due to the energy-dependent expression feature of P-gp, the damage to mitochondria inhibit P-gp expression, thus inhibit the efflux. (9) The targeted and mitochondria interrupted cell damaging pathway allow PDC to exert toxicity both wild type and drug resistant

Initiated by the interaction between AP2H and membrane-anchored LAPTM4B protein, PDC specifically recognized and bound cancer cells. The receptor-mediated endocytic pathway then led to the delivery of PDC to lysosomes. The low pH environment in lysosomes efficiently cut the hydrazone bond and released TPP-DOX. The successful escape from lysosomes enabled further transportation of TPP-DOX to mitochondria directed by targeting group TPP. Because TPP-DOX is highly active in producing ROS and mitochondria are prone to oxidative damage, the disruption in the electron transport chain and ATP synthesis finally lead to mitochondrial dysfunction and cell death. With dual-targeting ability, PDC can effectively bypass the interaction with P-gp. Meanwhile, due to the energy-dependent expression feature of P-gp, the damage to mitochondria inhibit P-gp expression, thus inhibit the efflux. (9) The targeted and mitochondria interrupted cell damaging pathway allow PDC to exert toxicity both wild type and drug resistant

Initiated by the interaction between AP2H and membrane-anchored LAPTM4B protein, PDC specifically recognized and bound cancer cells. The receptor-mediated endocytic pathway then led to the delivery of PDC to lysosomes. The low pH environment in lysosomes efficiently cut the hydrazone bond and released TPP-DOX. The successful escape from lysosomes enabled further transportation of TPP-DOX to mitochondria directed by targeting group TPP. Because TPP-DOX is highly active in producing ROS and mitochondria are prone to oxidative damage, the disruption in the electron transport chain and ATP synthesis finally lead to mitochondrial dysfunction and cell death. With dual-targeting ability, PDC can effectively bypass the interaction with P-gp. Meanwhile, due to the energy-dependent expression feature of P-gp, the damage to mitochondria inhibit P-gp expression, thus inhibit the efflux. (9) The targeted and mitochondria interrupted cell damaging pathway allow PDC to exert toxicity both wild type and drug resistant

Initiated by the interaction between AP2H and membrane-anchored LAPTM4B protein, PDC specifically recognized and bound cancer cells. The receptor-mediated endocytic pathway then led to the delivery of PDC to lysosomes. The low pH environment in lysosomes efficiently cut the hydrazone bond and released TPP-DOX. The successful escape from lysosomes enabled further transportation of TPP-DOX to mitochondria directed by targeting group TPP. Because TPP-DOX is highly active in producing ROS and mitochondria are prone to oxidative damage, the disruption in the electron transport chain and ATP synthesis finally lead to mitochondrial dysfunction and cell death. With dual-targeting ability, PDC can effectively bypass the interaction with P-gp. Meanwhile, due to the energy-dependent expression feature of P-gp, the damage to mitochondria inhibit P-gp expression, thus inhibit the efflux. (9) The targeted and mitochondria interrupted cell damaging pathway allow PDC to exert toxicity both wild type and drug resistant

Initiated by the interaction between AP2H and membrane-anchored LAPTM4B protein, PDC specifically recognized and bound cancer cells. The receptor-mediated endocytic pathway then led to the delivery of PDC to lysosomes. The low pH environment in lysosomes efficiently cut the hydrazone bond and released TPP-DOX. The successful escape from lysosomes enabled further transportation of TPP-DOX to mitochondria directed by targeting group TPP. Because TPP-DOX is highly active in producing ROS and mitochondria are prone to oxidative damage, the disruption in the electron transport chain and ATP synthesis finally lead to mitochondrial dysfunction and cell death. With dual-targeting ability, PDC can effectively bypass the interaction with P-gp. Meanwhile, due to the energy-dependent expression feature of P-gp, the damage to mitochondria inhibit P-gp expression, thus inhibit the efflux. (9) The targeted and mitochondria interrupted cell damaging pathway allow PDC to exert toxicity both wild type and drug resistant

Initiated by the interaction between AP2H and membrane-anchored LAPTM4B protein, PDC specifically recognized and bound cancer cells. The receptor-mediated endocytic pathway then led to the delivery of PDC to lysosomes. The low pH environment in lysosomes efficiently cut the hydrazone bond and released TPP-DOX. The successful escape from lysosomes enabled further transportation of TPP-DOX to mitochondria directed by targeting group TPP. Because TPP-DOX is highly active in producing ROS and mitochondria are prone to oxidative damage, the disruption in the electron transport chain and ATP synthesis finally lead to mitochondrial dysfunction and cell death. With dual-targeting ability, PDC can effectively bypass the interaction with P-gp. Meanwhile, due to the energy-dependent expression feature of P-gp, the damage to mitochondria inhibit P-gp expression, thus inhibit the efflux. (9) The targeted and mitochondria interrupted cell damaging pathway allow PDC to exert toxicity both wild type and drug resistant

Initiated by the interaction between AP2H and membrane-anchored LAPTM4B protein, PDC specifically recognized and bound cancer cells. The receptor-mediated endocytic pathway then led to the delivery of PDC to lysosomes. The low pH environment in lysosomes efficiently cut the hydrazone bond and released TPP-DOX. The successful escape from lysosomes enabled further transportation of TPP-DOX to mitochondria directed by targeting group TPP. Because TPP-DOX is highly active in producing ROS and mitochondria are prone to oxidative damage, the disruption in the electron transport chain and ATP synthesis finally lead to mitochondrial dysfunction and cell death. With dual-targeting ability, PDC can effectively bypass the interaction with P-gp. Meanwhile, due to the energy-dependent expression feature of P-gp, the damage to mitochondria inhibit P-gp expression, thus inhibit the efflux. (9) The targeted and mitochondria interrupted cell damaging pathway allow PDC to exert toxicity both wild type and drug resistant