Design and Investigation of Core/Shell GQDs/hMSN Nanoparticles as an Enhanced Drug Delivery Platform in Triple-Negative Breast Cancer.

Due to the excellent photoluminescent properties and singlet oxygen (1O2) generating efficiency, graphene quantum dots (GQDs) with maximal emission in near-infrared region (NIR) exhibited great potential in cancer imaging and therapy. However, GQDs can be cleared quickly via the renal system in vivo because of their ultrasmall size, which leads to the compromised cancer cell killing efficacy. Here, we report a hybrid nanoplatform, where GQDs were incorporated into the cavity of hollow mesoporous silica nanoparticles (hMSN) to form GQDs@hMSN-PEG nanoparticles (NPs). Optical characterization indicated that GQDs@hMSN-PEG NPs still maintained good absorption and emission properties from GQDs, and the composite NPs still possessed similar 1O2 generating efficiency. GQDs@hMSN-PEG NPs exhibited good biocompatibility in vitro and in vivo. High cargo-loading efficiency was achieved for doxorubicin (DOX), and the formed GQDs@hMSN(DOX)-PEG NPs showed the feasibility of tumor-oriented drug delivery. The extended retention time in tumor and good drug loading efficacy confirmed that GQDs@hMSN-PEG could serve as one promising candidate for combinational cancer treatment where photodynamic therapy and chemotherapy modules can be integrated into one system.

High-stabilized polydopamine modified low eutectic fatty acids based on near-infrared response for breast cancer therapy.

Low eutectic of lauric acid and stearic acid is one of drug loading candidates for its phase transformation at a certain temperature. Herein we demonstrated a combined photothermal-chemotherapy for breast cancer with near-infrared (NIR) triggered phase transition materials (PCM), which was conjugated with polydopamine (PDA) as the photosensitive agent. The PCM nanoparticles had diameters of ~75 nm based on scanning electron microscope (SEM) and dynamic laser scattering (DLS) measurement. Systematic in vitro and in vivo studies have been performed to investigate the stability, biosafety, photothermal performance, and drug delivery and release of PCM conjugates. Temperature measurement confirmed the prepared PDA modified material still showed strong photothermal effect after five cycles, which was higher than that of IR780 conjugated ones. In vivo photothermal imaging showed that the temperature of the tumor site reached 50.8 °C after 3 h of intravenous injection of PCM conjugates. More effective therapy of near-infrared (NIR)-assisted PDA-M@PCM in 4T1 bearing mice was witnessed when compared with that of non-NIR-assisted ones. Enhanced therapy in 4T1 tumor was demonstrated in DOX-loaded PDA-M@PCM by fluorescence imaging. This NIR-triggered PCM based nanoplatform can serve as useful tool for light-assisted combined tumor therapy.

A natural polymer-based porous sponge with capillary-mimicking microchannels for rapid hemostasis.

Natural polymer materials have attracted great attention in the field of hemostasis because of their wide range of source, nontoxicity, hydrophilicity, and air permeability. In the present study, two natural polymers composed of carboxymethyl chitosan (CMCS) and sodium carboxymethylcellulose (CMCNa) plus γ-(2,3-epoxypropoxy) propytrimethoxysilane (KH560) that serves as a crosslinking agent were selected to synthesize a capillary-mimicking composite hemostatic (CCK) sponge with a low density, interconnected microchannel architecture, suitable mechanical strength, high resilience, and ultrastrong liquid absorption capacity. The introduction of a large number of hydrophilic carboxymethyl functional groups and the design of capillary-mimicking structures formed by the ice segregation-induced self-assembly (ISISA) process endowed the CCK sponges with an ultrastrong liquid absorption capacity, which significantly enhanced the hemostatic ability of the materials. Both in vivo and in vitro hemostatic experiments confirmed the potential of the CCK sponges to achieve rapid hemostasis. Additionally, cytotoxicity and hemolysis assays showed that the CCK sponges exhibited good biocompatibility and hemocompatibility. The possible hemostatic mechanism was also discussed in this study. In conclusion, the capillary-mimicking hemostatic sponge exhibits a high potential to induce rapid hemostasis in prehospital emergency and clinical settings. STATEMENT OF SIGNIFICANCE: In the present study, an oriented composite hemostatic (CCK) sponge with a capillary-mimicking structure formed by the ice segregation-induced self-assembly (ISISA) process was designed and used to achieve rapid hemostasis. The unique aligned microchannel structure of the sponge exhibited an ultrastrong capillary-mimicking action and endowed the prepared CCK hemostatic sponge with a strong liquid absorption capacity. By changing the proportion of raw materials, we could modify the unique capillary-mimicking structure with aligned microchannels. Two natural polymer-based materials with abundant hydrophilic groups were chosen to prepare the CCK sponge to fully utilize the characteristics of this structure. The oriented natural polymer-based porous sponge with capillary-mimicking microchannels exhibited a strong hemostatic ability in both in vivo and in vitro tests. The results showed that the CCK sponge with the capillary-mimicking structure has a high potential to achieve rapid hemostasis.

Wound therapy via a photo-responsively antibacterial nano-graphene quantum dots conjugate.

Common bacterial pathogens have become resistant to traditional antibiotics, representing an indispensable public health crisis. Photodynamic therapy (PDT), especially when common visible light sources are used as photodynamic power, is a promising bactericidal method. Based on the special photodynamic properties triggered by commonly available light emitting diode (LED) lamps, a kind of graphene quantum dots (GQDs) based composite system (termed GQDs@hMSN(EM)) was prepared through loading both GQDs and erythromycin (EM) into the hollow mesoporous silica nanoparticle (hMSN), aiming to achieve joint antimicrobial effect. Bacterial density experiments confirmed that GQDs@hMSN(EM) had combined antimicrobial effects from photodynamic effect and drug release on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In animal models, the healing degree of wounds infected by bacteria also confirmed that GQDs@hMSN(EM) group had the best therapeutic effect, with the significantly reduced inflammatory factors in blood. Different from traditional GQDs synthesized by solvothermal method, the as-prepared GQDs@hMSN can produce singlet oxygen (1O2) under light exposure to destroy the structure of bacteria, thus achieving highly efficient antimicrobial effect. The GQDs@hMSN(EM) in this work possesses good antimicrobial activity, sufficient drug loading, and controllable drug release ability, which provides a new opportunity for GQDs-based nanoplatform to enhance antimicrobial effect and reduce their drug resistance.

The effect of PEG functionalization on the in vivo behavior and toxicity of CdTe quantum dots.

CdTe quantum dots (QDs) are considered a potential toxic substance because they contain metal ions. However, most toxicology data are derived from in vitro studies or limited in vivo analysis and may not reflect in vivo responses and biodistribution. Proper modification is one of the most widely used routes to reduce the toxicity of QDs. Herein, we demonstrated the role of polyethylene glycol (PEG) in decreasing the toxicity of QDs by studying the animal survival, clinical biochemistry, organ histology, biodistribution and oxidative stress in thioglycolic acid (TGA)- and mercapto-acetohydrazide (TGH)-stabilized CdTe QD (TGA/TGH-CdTe QD)-treated groups. Via the histology, transmission electron microscopy (TEM) and biodistribution results, it was found that the QDs mainly accumulated in the liver and kidney at 7 days post-injection, and obvious tissue damage was also observed in the bare TGA/TGH-CdTe QD group. Based on the evaluation of oxidative stress in the liver and kidney, the indicators exhibited an obvious variation with a high dose of TGA/TGH-CdTe QDs. In contrast, the QD aggregation decreased in the liver and kidney with no clear physiological index variation after PEG functionalization. Thus, PEG plays an important role in decreasing the toxicity of the CdTe QDs, and both the accumulation of cadmium and oxidative stress variation instead of an isolation factor are responsible for the in vivo toxicity of these QDs.

In vivo targeting of breast cancer with a vasculature-specific GQDs/hMSN nanoplatform.

According to our previous experiment, graphene quantum dots capped in hollow mesoporous silica nanoparticles, denoted as GQDs@hMSN, and its conjugates exhibited great potential for medical applications due to their commendable biocompatibility. Due to the fluorescence and structural stability, and enormous porosity, polyethylene glycol (PEG) modified GQDs@hMSN (GQDs@hMSN-PEG) is a good candidate in a drug carrying and delivery system. However, the goal of targeted drug delivery couldn't be achieved simply by utilizing the enhanced permeability and retention (EPR) effect of tumors. In this study, GQDs@hMSN-PEG was further functionalized with vascular endothelial growth factor antibodies (VEGF Abs) for VEGF targeting of breast tumors. Doxorubicin (DOX) was loaded into GQDs@hMSN-VEGF Abs with a drug loading capacity of 0.80 mg DOX per mg GQDs@hMSN. With GQDs as the fluorescent source, GQDs@hMSN-VEGF Abs demonstrated strong fluorescence intensity in VEGF-positive cells. Results from in vitro and in vivo targeting experiments indicated that GQDs@hMSN-VEGF Abs had high specificity on tumor vasculature, and it could be used as an image-guidable, tumor-selective delivery nanoplatform for breast cancer.

Preparation of core/shell CdTe@hMSN for enhanced tumor vasculature-specific drug delivery.

Due to excellent optical properties, CdTe quantum dots (QDs) exhibit great potential in cancer imaging. However, CdTe QDs can be quickly cleared out before reaching the desired location because of their ultra-small size. The structure and optical properties of CdTe QDs are also easily affected by the surrounding solution, which leads to their compromised applications in vivo. Here, CdTe QDs were incorporated into hollow mesoporous silica nanoparticles (hMSN) to form CdTe@hMSN nano-platforms. The as-synthesized system maintained the excellent emission properties of CdTe QDs; meanwhile, relatively high drug loading efficiency was also observed for doxorubicin (DOX). With the target for vascular endothelial growth factor (VEGF), the formed CdTe@hMSN(DOX)-VEGF Abs showed feasibility of tumor-oriented drug delivery and CdTe@hMSN conjugate accumulation. The high accumulation and enhanced targeted drug delivery of CdTe@hMSN conjugates in tumor nodules confirmed that CdTe@hMSN conjugates can serve as promising candidates for cancer detection and treatment.