Early-stage brain metastasis of breast cancer(BMBC), due to the existence of an intact blood–brain barrier(BBB), is one of the deadliest neurologic complications. To improve the efficacy of chemotherapy for BMBC, a T...Early-stage brain metastasis of breast cancer(BMBC), due to the existence of an intact blood–brain barrier(BBB), is one of the deadliest neurologic complications. To improve the efficacy of chemotherapy for BMBC, a Trojan horse strategy-based nanocarrier has been developed by integrating the cell membrane of a brain-homing cancer cell and a polymeric drug depot. With the camouflage of a MDA-MB-231/Br cell membrane, doxorubicin-loaded poly(D, L-lactic-co-glycolic acid) nanoparticle(DOX-PLGA@CM) shows enhanced cellular uptake and boosted killing potency for MDA-MB-231/Br cells. Furthermore, DOX-PLGA@CM is equipped with naturally selected molecules for BBB penetration, as evidenced by its boosted capacity in entering the brain of both healthy and early-stage BMBC mouse models. Consequently, DOX-PLGA@CM effectively reaches the metastatic tumor lesions in the brain, slows down cancer progression, reduces tumor burden, and extends the survival time for the BMBC animal.Furthermore, the simplicity and easy scale-up of the design opens a new window for the treatment of BMBC and other brain metastatic cancers.展开更多
基金the National Institutes of Health(1R01AG054839-01A1,1R41CA254500-01A1,and 1R21CA252360-01)for financial support of the research。
文摘Early-stage brain metastasis of breast cancer(BMBC), due to the existence of an intact blood–brain barrier(BBB), is one of the deadliest neurologic complications. To improve the efficacy of chemotherapy for BMBC, a Trojan horse strategy-based nanocarrier has been developed by integrating the cell membrane of a brain-homing cancer cell and a polymeric drug depot. With the camouflage of a MDA-MB-231/Br cell membrane, doxorubicin-loaded poly(D, L-lactic-co-glycolic acid) nanoparticle(DOX-PLGA@CM) shows enhanced cellular uptake and boosted killing potency for MDA-MB-231/Br cells. Furthermore, DOX-PLGA@CM is equipped with naturally selected molecules for BBB penetration, as evidenced by its boosted capacity in entering the brain of both healthy and early-stage BMBC mouse models. Consequently, DOX-PLGA@CM effectively reaches the metastatic tumor lesions in the brain, slows down cancer progression, reduces tumor burden, and extends the survival time for the BMBC animal.Furthermore, the simplicity and easy scale-up of the design opens a new window for the treatment of BMBC and other brain metastatic cancers.
