Aixian Zheng

Multifunctional PEG modified DOX loaded mesoporous silica nanoparticle@CuS nanohybrids as photo-thermal agent and thermal-triggered drug release vehicle for hepatocellular carcinoma treatment

The combination of a multi-therapeutic mode with a controlled fashion is a key improvement in nanomedicine. Here, we synthesized polyethylene glycol (PEG)-modified doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) @CuS nanohybrids as efficient drug delivery carriers, combined with photothermal therapy and chemotherapy to enhance the therapeutic efficacy on hepatocellular carcinoma (HCC). The physical properties of the nanohybrids were characterized by transmission electron microscopy (TEM), N2 adsorption and desorption experiments and by the Vis-NIR absorption spectra. The results showed that the doxorubicin could be stored in the inner pores of mesoporous silica nanoparticles; the CuS nanoparticles, which are coated on the surface of a mesoporous silica nanoparticle, could serve as efficient photothermal therapy (PTT) agents; the loaded drug release could be easily triggered by NIR irradiation. The combination of the PTT treatment with controlled chemotherapy could further enhance the cancer ablation ability compared to any of the single approaches alone. Hence, the reported PEG-modified DOX-loaded mesoporous silica nanoparticle@CuS nanohybrids might be very promising therapeutic agents for HCC treatment.

Tumor Microenvironment Activable Self-Assembled DNA Hybrids for pH and Redox Dual-Responsive Chemotherapy/PDT Treatment of Hepatocellular Carcinoma

Smart self‐assembled “Turn‐ON” DNA hybrids are employed, which could respond to tumor microenvironment stimuli for cancer cell specific real‐time fluorescence imaging, tumor‐specific synergistic photodynamic therapy and chemotherapy in hepatocellular carcinoma.

Horseradish peroxidase and aptamer dual-functionalized nanoprobe for the amplification detection of alpha-methylacyl-CoA racemase.

Alpha-methylacyl-CoA racemase (AMACR) is over-expressed in many cancer types and can serve as a novel diagnostic biomarker. Development of convenient and sensitive detection methods of AMACR is of particular importance for cancer diagnosis. Aptamers are a type of recognition elements, which possess many advantages over antibody, making them suitable for applications in biosensing and biotechnology. In this work, we use the efficient surface modification of gold nanoparticles (AuNPs) to prepare the horseradish peroxidase (HRP) and aptamer dual-functionalized nanoprobe. The immobilization of HRP and thiol-terminated aptamer on the surface of AuNPs can be achieved through electrostatic interaction and the formation of Au-S bond, respectively. This nanoprobe, which is used as discriminating and catalytic probe, can be combined with enzyme immunoassay method to increase the detection sensitivity of AMACR. The detection limit can reach as low as 4.6 pg mL(-1) due to the dual signal amplification from enzymatic cycling and the high loading of enzymes on AuNPs. This sensitivity is about three orders of magnitude higher than that of AMACR aptamer based fluorescence method, which is also comparable to or one order of magnitude higher than that of ELISA. Furthermore, this method is more simple and effective, which not only avoids the conjugation between recognition element and the catalytic enzyme, but also achieves greater signal amplification. This assay could be used as a sensitive and selective platform for the detection of target protein.

Photoresponsive Nanovehicle for Two Independent Wavelength Light-Triggered Sequential Release of P-gp shRNA and Doxorubicin To Optimize and Enhance Synergistic Therapy of Multidrug-Resistant Cancer

Prerelease of RNA molecules than chemotherapeutic drugs with a sufficient interval is a vital prerequisite for RNA/drug co-delivery strategy to overcome multidrug resistance (MDR) of cancer cells, but how to precisely control their release at different time points is still a grand challenge up to now. This study aims to on-demand remotely manipulate RNA and drug release in real time through single delivery system to sequentially play their respective roles for optimizing and enhancing their synergistic antitumor effects. To this end, a photoresponsive mesoporous silica nanoparticle (PMSN) is fabricated as a co-delivery vehicle of P-glycoprotein (P-gp) short-hairpin RNA (shRNA) and photocaged prodrug of doxorubicin (DOX), by which the orthogonal and sequential release of shRNA and DOX can be achieved using an external light. In our design, the cationic poly[2-( N, N-dimethylaminoethyl)methacrylate] is introduced onto the PMSN surface through a light-sensitive coumarin ester derivative linker to adsorb P-gp shRNA, whereas the photocleavable o-nitrobenzyl ester derivative-caged DOX is loaded into the inner pores of the PMSN. The PMSN is found to be effectively internalized by MDR cancer cells, and the release of the shRNA and DOX is demonstrated to be independently regulated by 405 and 365 nm light irradiations due to selectively cleaved coumarin and o-nitrobenzyl ester, resulting in enhanced drug retention, and finally bring out optimized and significantly improved chemotherapeutic effects both in vitro and in vivo for MDR cancer treatment, which might hold extensive application prospects in MDR cancer treatment in future.

Multifunctional human serum albumin-modified reduced graphene oxide for targeted photothermal therapy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancer worldwide, and has a high degree of malignancy and poor prognosis. Early diagnosis and treatment of HCC would significantly improve clinical outcomes. Near infrared (NIR) laser and photo-absorbing agent-based photothermal therapy (PTT) is an emerging therapeutic hyperthermia approach, and has been suggested as a minimally invasive and highly efficient therapeutic method. Reduced graphene oxide (rGO) is one of the most typical photothermal agents. Compared with other materials, rGO possesses some advantages, such as simple synthesis, low cost, high photo-stability and large surface area for drug loading. However, rGO exhibits poor dispersibility and difficult modification due to loss of the hydrophilic functional groups during the reduction process. Thus, the modification processes of rGO are always complicated, time-consuming, and require some expensive polymers. In this paper, human serum albumin (HSA) was functionalized with indocyanine green (ICG) and lactobionic acid (LA) to prepare multifunctional human serum albumin (mfHSA), which could be used for the modification of rGO. This approach is simple and highly efficient, and not only improves the stability and the biocompatibility of rGO, but also makes it exhibit an enhanced photothermal conversion efficiency and targeting specificity towards HCC cells. The low cytotoxicity and the high PTT therapeutic efficacy at both the cellular and animal levels indicated that the prepared multifunctional nanomaterials could serve as a highly effective therapeutic agent for HCC.

Polydopamine-assisted versatile modification of a nucleic acid probe for intracellular microRNA imaging and enhanced photothermal therapy

MicroRNAs play an important role in various biological processes, and their aberrant expression is closely associated with various human diseases, especially cancer. Real-time monitoring of microRNAs in living cells may help us to understand their role in cellular processes, which can further provide a basis for diagnosis and treatment. In this study, polydopamine was used to assist the versatile modification of a nucleic acid probe for intracellular microRNA imaging and enhanced photothermal therapy. Polydopamine can be covalently linked with a thiol-terminated nucleic acid probe through the Michael addition reaction under slightly alkaline conditions. This modification is mild and can be performed directly in an aqueous solution, which can better resist hydrolysis than the traditional modification processes, resulting in a nanoprobe with better stability and higher loading of nucleic acids. This prepared nanoprobe can easily enter cells without transfection agents and then realize the imaging of intracellular miRNA through fluorescence restoration. Moreover, the coating of PDA can enhance the photothermal conversion efficiency of the nanoprobe, making it suitable for photothermal therapy of cancer. It is expected that the PDA-based versatile modification can help to construct a promising platform for tumor imaging and treatment.