| Cancer poses a serious threat to human health because of traditional chemotherapy is difficult to achieve the ideal therapeutic effect.Impressively,tissue engineering scaffold not only can guide tissue regeneration by regulating cell behavior,but also satisfy drug target delivery as a drug carrier.Therefore,the drug loaded tissue engineering scaffold possess great potential in cancer therapy due to combining anti-tumor and tissue repair.Based on this,the multi-function drug loaded scaffold was constructed by loading the doxorubicin(DOX)in lamellar nanohydroxyapatite(LHAp)and poly(lactic-co-glycolic acid)(PLGA)nanofiber and modifying by polydopamine(PDA)coating.In order to improving the anti-tumor effect,the siBcl-2(gene drug)was loaded on the modified DOX-loaded LHAp/PLGA nanofiber scaffold(DOX@LHAp/PLGA)to fabricating a multi-mode drug-loaded tissue engineering scaffold integrated chemotherapy with gene therapy.So that,the anti-tumor research in vivo and in vitro was carried out in this paper.Firstly,DOX was intercalated into the LHAp because the highly ordered structure and larger interlayer space of LHAp.Then,the DOX-loaded LHAp was mixed with PLGA and electrospun to yield DOX@LHAp/PLGA scaffolds(DH/PLGA).Importantly,in order to reach dual functions of tumor inhibition and bone repair,the PDA was used to modify the DH/PLGA scaffold inspired by mussels.It is found that PDA coating not only improves hydrophilicity and mechanical properties,but also achieve the purpose of sustained and controlled release.Impressively,the PDA@DH/PLGA scaffold shows significantly inhibited growth of tumor cells initially and subsequent improved adhesion and proliferation of osteoblasts.In addition,the PDA coating improves the bioactivity of the DH/PLGA scaffold as suggested by the in vitro biomineralization.Further in vivo study demonstrates the improved bone growth around PDA@DH/PLGA over DH/PLGA.The dual functional PDA@DH/PLGA scaffold shows a great promise in the treatment of bone tumor.Secondly,The PDA-modified DH/PLGA scaffolds was loaded polyethylenimine(PEI)/siRNA in order to address the issue of drug chemotherapy in the treatment of tumor.The double drug loaded tissue engineering scaffold with multi-mode therapy both chemotherapy and gene was obtained.It is showed that the ratio of weight loss of scaffold can reach 30% after 8 weeks of degradation,and the DOX and siRNA could be controlled released for more than 10 days.The results of in vitro anti-tumor confirmed that the double drug loaded scaffold displayed great anti-tumor properties than DH/PLGA scaffold.It is worth noting that the human ovarian cancer model was constructed in mice,and the double drug loaded scaffold was implanted into the tumor to study its anti-tumor effect in vivo.It is found that the scaffold can not only successfully transport siRNA into tumor cells and knock out Bcl-2 gene to achieve gene therapy,but also sustained release DOX to achieve the purpose of chemotherapy,which can effectively inhibit the growth of tumor in vivo.In conclusion,the drug loaded tissue engineering scaffolds were fabricated by electrospinning DOX-loaded LHAp into PLGA nanofibers.The multi-function and multi-mode collaborative therapy scaffold was constructed by using surface modification.The modified drug loaded tissue engineering scaffolds has great potential in a wide variety of applications of anti-tumor effect. |
