Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 10, Issue 10, Pages 8555-8565Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b00875
Keywords
celecoxib; doxorubicin; human serum albumin; nanoparticles; enhanced cancer therapy
Funding
- National Natural Science Foundation of China [51690151, 51503122, 51473093]
- National Basic Research Program [2015CB931801]
- Shanghai Rising-Star Program [17QC1401100]
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Recent years have witnessed the great contributions that drug combination therapy has made for enhanced cancer therapy. However, because of the complicated pharmacokinetics of combined drug formulations, the majority of combination strategies show severe adverse effects at high dosage and poor biodistribution in vivo. To overcome these deficiencies and achieve enhanced cancer therapy, we put forward a method to construct a smart albumin-based nanoplatform, denoted as K237-HSA-DC, for codelivery of cyclooxygenase-2 (COX-2) inhibitor (celecoxib) and chemotherapeutic agent (doxorubicin, DOX). Both in vitro and in vivo studies indicate that K237-HSA-DC exhibits the best therapeutic efficacy on tumor cells compared with all the other formulations. Moreover, K237-HSA-DC shows fewer side effects on normal organs in contrast to other formulations. To understand the reasons behind the improved drug efficacy in depth, we performed a cell metabonomics-based mechanism study and found that celecoxib could enhance the inhibitory effect of DOX on the transport of glucose into cells and then lead to subsequent significant energy metabolism inhibition. Considering the above-mentioned advantages of K237-HSA-DC, we believe the smart albumin-based nanoplatform can serve as a promising drug delivery system for enhanced cancer therapy.
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