Issue

Vol. 14 (2022)

A Therapeutic Sheep in Metastatic Wolf’s Clothing: Trojan Horse Approach for Cancer Brain Metastases Treatment

https://doi.org/10.1007/s40820-022-00861-1
Hai‑jun Liu
Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA
Mingming Wang
Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA
Shanshan Shi
Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA
Xiangxiang Hu
Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA
Peisheng Xu
Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA

Corresponding Author: Peisheng Xu

xup@cop.sc.edu

Nano-Micro Letters, Vol. 14 (2022), Article Number: 114

Abstract

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.


Highlights:


1 DOX-PLGA@CM employs the whole set of membrane molecules of a brain-homing metastatic breast cancer cell optimized through a natural selection process. Thus, the hetero and multivalent effects of these molecules greatly facilitate the nanoparticle crossing the blood-brain barrier.
2 Attributed to the homotypic effect of the nanocarrier, DOX-PLGA@CM shows stronger anticancer efficacy than free DOX for its parenteral cells.
3 DOX-PLGA@CM effectively reaches the metastatic tumor lesions in the brain, and slows down the progression of brain metastatic breast cancer.

Keywords

Trojan horse Brain metastasis Blood–brain barrier Cell membrane Nanomedicine
Liu, Hai‑jun, Mingming Wang, Shanshan Shi, Xiangxiang Hu, and Peisheng Xu. 2022. “A Therapeutic Sheep in Metastatic Wolf’s Clothing: Trojan Horse Approach for Cancer Brain Metastases Treatment”. Nano-Micro Letters 14 (April):114. https://doi.org/10.1007/s40820-022-00861-1.
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