Abstract
This work reports a multifunctional nanocarrier based on hollow mesoporous silica nanoparticles (HMSNs) for targeting tumor therapy. Doxorubicin (DOX) was loaded into HMSNs and blocked with cytochrome C conjugated lactobionic acid (CytC–LA) via redox-cleavable disulfide bonds and pH-disassociation boronate ester bonds as intermediate linkers. The CytC–LA was used both as sealing agent and targeting motif. A series of characterizations demonstrated the successful construction of the drug delivery system. The system demonstrated pH and redox dual-responsive drug release behavior in vitro. The DOX loading HMSNs system displayed a good biocompatibility, which could be specifically endocytosed by HepG2 cells and led to high cytotoxicity against tumor cells by inducing cell apoptosis. In vivo data (tumor volume, tumor weight, terminal deoxynucleotidyl transferase dUTP nick end labeling and hematoxylin and eosin staining) proved that the system could deliver DOX to tumor site with high efficiency and inhibit tumor growth with minimal toxic side effect.
Highlights
Tumor is one of the most severe disease that causing human death worldwide [1]
Cytochrome C (CytC)–lactobionic acid (LA) was grafted onto the hollow mesoporous silica nanoparticles (HMSNs) system through boronate ester bonds (Fig. S1, see online supplementary material for a colour version of this figure), which was sensitive to the acidic stimulus
Previous studies confirmed that nanoparticles with dimensions below 200 nm could be well circulated in vivo and endocytosed with high efficiency for drug delivery [4]
Summary
Tumor is one of the most severe disease that causing human death worldwide [1]. conventional therapies (chemotherapy and radiotherapy, etc.) could treat tumors to some degrees, it was proved that those therapies had severe damage or toxicity against healthy organs [2], due to being lack of cell specificity. To further simulate the intracellular environment of tumor cells, the HMSNs–S–S–CPA–CytC– LA@DOX system was dispersed into the PBS (pH 5.0) mixing with GSH (10 mM), resulting in rapid drug release of about 89% in 12 h. After incubation with medium containing HMSNs, HMSNs–S–S–CPA–CytC and HMSNs–S–S– CPA–CytC–LA for 6, 12 and 24 h, no significance difference of cells viability was observed when comparing with that of cells cultured on TCPS plates (control) at different time intervals (Fig. 3A), indicating the good cytocompatibility of different HMSNs. we performed the dose-dependent cytotoxicity assay of HMSNs–S–S–CPA–CytC–LA@DOX system.
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