Abstract
Multi-drug nanomedicine is gaining momentum for co-delivering more than one drug to the same site at the same time. Our analysis of 273 pre-clinical tumour growth inhibition studies shows that multi-drug nanotherapy outperforms single-drug therapy, multi-drug combination therapy, and single-drug nanotherapy by 43, 29 and 30%, respectively. Combination nanotherapy also results in the best overall survival rates, with 56% of studies demonstrating complete or partial survival, versus 20-37% for control regimens. Within the multi-drug nanomedicine groups, we analysed the effect of (co-)administration schedule and strategy, passive versus active targeting, nanocarrier material and the type of therapeutic agent. Most importantly, it was found that co-encapsulating two different drugs in the same nanoformulation reduces tumour growth by a further 19% compared with the combination of two individually encapsulated nanomedicines. We finally show that the benefit of multi-drug nanotherapy is consistently observed across different cancer types, in sensitive and resistant tumours, and in xenograft and allograft models. Altogether, this meta-analysis substantiates the value of multi-drug nanomedicine as a potent strategy to improve cancer therapy.