<p>Multimodal Mesoporous Silica Nanocarriers for Dual Stimuli-Responsive Drug Release and Excellent Photothermal Ablation of Cancer Cells</p>

Abstract

Background: Core-shell types of mesoporous silica nanoparticles (MSNs) with multimodal functionalities were developed for bio-imaging, controlled drug release associated with external pH, and near-infrared radiation (NIR) stimuli, and targeted and effective chemo-photothermal therapeutics. Materials and Methods: We synthesized and developed a core-shell type of mesoporous silica nanocarriers for fluorescent imaging, stimuli-responsive drug release, magnetic separation, antibody targeting, and chemo-photothermal therapeutics. Also, the biocompatibility, cellular uptake, cytotoxicity, and photothermal therapy on these FS3-based nanocarriers were systematically investigated. Results: Magnetic mesoporous silica nanoparticles was prepared by coating a Fe 3 O 4 core with a mesoporous silica shell, followed by grafting with fluorescent conjugates, so-called FS3. The resulting FM3 was preloaded with therapeutic cisplatin and coated with polydopamine layer, socalled FS3P/C. Eventually, graphene oxide-wrapped FS3P/C (FS3P-G/C) exhibited high sensitivity in the dual stimuli (pH, NIR)-responsive controlled release behavior. On the other hand, Au NPs-coated FS3P/C (FS3P-A/C) exhibited more stable release behavior, irrespective of pH changes, and exhibited much more enhanced release rate under the same NIR irradiation. Notably, FS3P-A/C showed strong NIR absorption, enabling photothermal destruction of HeLa cells by its chemo-photothermal therapeutic effects under NIR irradiation (808 nm, 1.5 W/cm 2). The selective uptake of FS3-based nanocarriers was confirmed in cancer cell lines including HeLa (American Type Culture Collection-ATCC) and SHSY5Y (ATCC 2266) by the images obtained from confocal laser scanning microscopy, flow cytometry, and transmission electron microscopy instruments. Cisplatin-free FS3-based nanocarriers revealed good cellular uptake and low cytotoxicity against cancerous HeLa and SH-SY5Y cells, but showed no obvious toxicity to normal HEK293 (ATCC 1573) cell. Conclusion: Along with the facile synthesis of FS3-based nanocarriers, the integration of all these strategies into one single unit will be a prospective candidate for biomedical applications, especially in chemo-photothermal therapeutics, targeted delivery, and stimuliresponsive controlled drug release against multiple cancer cell types.

pH-triggered degradation and release of doxorubicin from zeolitic imidazolate framework-8 (ZIF8) decorated with polyacrylic acid

“…[12][13][14][15] ZIF8 possesses extra-high porosity, chemical and thermal stability, biocompatibility, and easily controllable size and shape. [16][17][18] Multifunctional ZIF8 nanomaterials have adaptability and responsiveness to various endogenous stimuli (e.g., pH, enzyme, and redox gradients) [19][20][21][22][23][24][25] and exogenous stimuli (e.g., temperature, magnetic eld, and light) [26][27][28][29] and controllable drug release for disease therapy and cell imaging. 24,30 Additionally, ZIF8 nanocarriers can have various nanomedicine applications, such as targeting cancer cells with hyaluronic acid conjugates, 31 magnetic resonance and uorescence imaging using uorescein isothiocyanate (FITC), 19 and controlled drug release by graphene oxide.…”

Progress in Mesoporous Silica Nanoparticles as Drug Delivery Agents for Cancer Treatment

“…The antibody was attached to the graphene oxide (GO) surface of MSNs composite. The result showed that with antibody conjugation, the carrier was internalized and retained in HeLa cells, and this indicated the effectiveness of the antibody in cancel targeting and treatment [ 139 ]. The FDA-approved antibody trastuzumab, which targets the HER2 receptor, was conjugated with MSNs to target breast cancer cells [ 140 , 141 , 142 ].…”

Nanoplatforms for Sepsis Management: Rapid Detection/Warning, Pathogen Elimination and Restoring Immune Homeostasis

“…Integrating multiple types of metallic/inorganic NPs into one unit enables synergistic enhancement in rational drug delivery, and consequently overcomes the limitations of conventional drug delivery platforms. Tran and coworkers fabricated a core–shell magnetic mSiO 2 NPs that comprise a Fe 3 O 4 core and a mSiO 2 coating with graft of fluorescent conjugates [ 78 ]. After drug loading and surface coating of polydopamine, they found further wrapping with graphene oxide layer and subsequent antibody functionalization exhibit more stable release behavior, active targeting feature, and dual stimuli-response to pH and near-infrared radiation (NIR), whereas coating with AuNPs layer will additionally support excellent photothermal therapy (PTT) due to nanoplasmonic effect [ 78 ].…”

“…Tran and coworkers fabricated a core–shell magnetic mSiO 2 NPs that comprise a Fe 3 O 4 core and a mSiO 2 coating with graft of fluorescent conjugates [ 78 ]. After drug loading and surface coating of polydopamine, they found further wrapping with graphene oxide layer and subsequent antibody functionalization exhibit more stable release behavior, active targeting feature, and dual stimuli-response to pH and near-infrared radiation (NIR), whereas coating with AuNPs layer will additionally support excellent photothermal therapy (PTT) due to nanoplasmonic effect [ 78 ]. Similarly, ZnO quantum dots (QDs) with pH-responsive and gatekeeping features can be integrated into plasmonic AuNP@mSiO 2 nanocomposites, thus simultaneously enabling PTT and on-demand release of therapeutic doxorubicin (DOX) [ 79 ].…”