In situ adjuvant therapy using a responsive doxorubicin-loaded fibrous scaffold after tumor resection

Abstract As tumor microenvironment becoming more and more important in tumor study, the acid pH around or in solid tumors drew lots of attentions. And the progress of drug delivery systems made the responsive-release possible. This time, we fabricated a new-type composite electrospun poly (L-lactide) (PLLA) fibrous scaffolds, that blent with the mesoporous silica particles (MSNs). Further more, we used sodium bicarbonate (SB) as acid sensitive agent which was wrapped inside the MSNs. And doxorubicin (DOX) was also wrapped into MSNs in order to achieve a sustained release to inhibit tumors in mice, which mimicked the remnant breast cancer with surgery. In vitro experiments proved the characteristic of pH-responsive release of the composite fibrous scaffold. In vivo results showed that these composite fibers could induce obvious apoptosis and necrosis over 10 weeks. Further, the cancer-kill effects were also confirmed by the decreased level of Bcl-2 and TNF-α, while increased Bax and caspase-3 expression levels. Altogether, the results indicated that the composite drug delivery system as a local implantable scaffold could effectively kill cancer cells in a long term with pH-sensitivity after the tumor resection.