A multifunctional envelope-type mesoporous silica nanoparticle (MSN) was delicately designed for subcellular co-delivery of drug and therapeutic peptide to tumor cells. Firstly, a kind of cell apoptosis peptide (KLAKLAK) 2 (KLA) was anchored on surface of MSN via disulfide bond to obtain MSN-SS-KLA. Subsequently, anticancer drug doxorubicin hydrochloride (DOX) was loaded into the pores of MSN-SS-KLA. Then, the drug loaded MSN-SS-KLA (DOX@MSN-SS-KLA) was further coated with bovine serum albumin (BSA) to obtain a biological media stable MSN based drug delivery system (DDS), DOX@MSN-SS-KLA/BSA, for cancer synergetic therapy. The results show that stability of the DOX@MSN-SS-KLA/BSA is much better than that of DOX@MSN-SS-KLA and it could keep well dispersed in serum for more than 24 h. After accumulating at tumor site by EPR effect, the DOX@MSN-SS-KLA/BSA could be effectively phagocytosed by HeLa cells and release apoptotic peptide KLA as well as DOX simultaneously responding to reductive stimulus inside the cells. In vitro cell experiment results show that the DOX@MSN-SS-KLA/BSA complex exhibits much better inhibition on HeLa cells compared with pure DOX, indicating that co-delivery of KLA and DOX is expected to achieve synergetic therapy of cancer.
Han Hu,Ruiqi Li,Piao Huang,Zhimin Mo,Qi Xu,Tao Hu,Shijie Yao,Xiaofang Dai,Zushun Xu
Photodynamic therapy (PDT) has many exceptional advantages in cancer treatment, such as minor trauma, low toxicity side effects, and strong adaptability, effectively overcoming some obstacles of traditional therapy and providing more revolutionary opportunities for curing cancer. Chlorin e6 (Ce6) exhibits excellent singlet oxygen generation and conversion efficiency under near-infrared laser irradiation and is a promising PDT photosensitizer. However, its hydrophobicity, short half-life and lack of tumor specificity limit its in vivo anticancer application. Therefore, this work has designed and prepared a multifunctional nanoplatform, Ce6/ [email protected] , to efficiently deliver Ce6. Nanoparticles exhibit excellent dispersion and stability in deionized water, PBS and DMEM, and the blood half-life is 3.98 ± 0.31 h. The nanoplatform demonstrates effective tumor targeting and accumulation, overcoming the obstacles of the biological application of Ce6. Iron ions can exert a chemodynamic therapy (CDT) effect by reacting with overexpressed H 2 O 2 in the tumor to generate toxic hydroxyl radicals (·OH). Moreover, FeOOH nanoparticles effectively promote glutathione (GSH) consumption in tumor cells, which is conducive to accumulating reactive oxygen species (ROS). In brief, Ce6/ [email protected] nanoparticles realize the targeted delivery of Ce6 and mediate synergistic PDT/CDT against tumors, broadening the biomedical application of nanomaterials.
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