Near-infrared aggregation-induced emission nanodots for early diagnosis of tongue squamous cell carcinoma and sentinel lymph node mapping.

Fluorescence imaging has been widely used in the biomedical field owing to its merits of high sensitivity, excellent accuracy, high biosafety, etc. However, despite the good performance of fluorescent materials in the diagnosis of subcutaneous tumors or some orthotopic tumors in mice, their potential clinical application for most orthotopic tumors in humans is still limited due to their weak tissue penetration ability and the high thickness of human tissues. Given that the human tongue can extend out of the mouth and is approximately 1 cm thick, the diagnosis of tongue squamous cell carcinoma (TSCC) by fluorescence has great potential for clinical applications. However, to the best of our knowledge, a few studies have been performed to detect tongue tumors using fluorescence imaging, and most of them are administered in a subcutaneous tumor-bearing mouse model and are based on fluorescent materials with aggregation-caused quenching effects. Herein, by developing DPA-TPE-DCM with intense near-infrared fluorescence emission in the aggregation state, aggregation-induced emission materials were used for the first time in the early diagnosis of orthotopic TSCC and sentinel lymph node (SLN) mapping in an immunocompetent mouse model of orthotopic TSCC with a high signal-to-background ratio of 10.2. Moreover, with the guidance of the fluorescence of DPA-TPE-DCM NPs, SLNs smaller than 2 mm in diameter were successfully excised. This study provides new insight and a method for the early diagnosis of TSCC in clinical practice and provides more possibilities to broaden the potential clinical applications of fluorescent materials.

Polymeric Nitric Oxide Delivery Nanoplatforms for Treating Cancer, Cardiovascular Diseases, and Infection.

The shortened Abstract is as follows: Therapeutic gas nitric oxide (NO) has demonstrated the unique advances in biomedical applications due to its prominent role in regulating physiological/pathophysiological activities in terms of vasodilation, angiogenesis, chemosensitizing effect, and bactericidal effect. However, it is challenging to deliver NO, due to its short half-life (<5 s) and short diffusion distances (20-160 µm). To address these, various polymeric NO delivery nanoplatforms (PNODNPs) have been developed for cancer therapy, antimicrobial and cardiovascular therapeutics, because of the important advantages of polymeric delivery nanoplatforms in terms of controlled release of therapeutics and the extremely versatile nature. This reviews highlights the recent significant advances made in PNODNPs for NO storing and targeting delivery. The ideal and unique criteria that are required for PNODNPs for treating cancer, cardiovascular diseases and infection, respectively, are summarized. Hopefully, effective storage and targeted delivery of NO in a controlled manner using PNODNPs could pave the way for NO-sensitized synergistic therapy in clinical practice for treating the leading death-causing diseases.

Root Canal Disinfection Using Highly Effective Aggregation-Induced Emission Photosensitizer.

Root canal (RC) therapy is the primary treatment of dental-pulp and periapical diseases. The mechanical method and chemical irrigation have limitations in RC therapy. Much attention has focused on exploring more controllable and efficacious antimicrobial methods. Although the introduction of photodynamic therapy (PDT) has provided the ideas for RC debridement, the problems of low photosensitive efficiency and nonsignificant germicidal potency of traditional photosensitizers (e.g., methylene blue) have not been solved. Since the concept of "aggregation-induced emission" (AIE) was proposed, optimization of photosensitizers has been boosted considerably. Herein, an AIE photosensitizer, DPA-SCP, with a strong ability to generate singlet oxygen, is proposed for use as an antibacterial application in infected RCs. The antimicrobial activity of DPA-SCP against Enterococcus faecalis suspensions was tested. To explore the antibacterial ability of this photosensitizer against bacterial-biofilm colonization on the inner walls of RCs, we established a model of bacterial biofilm infection. PDT mediated by DPA-SCP had a significant germicidal effect on E. faecalis suspensions and 21-day biofilms in human RCs. PDT mediated by DPA-SCP could achieve efficiency equivalent to that observed using 1% NaOCl, and lead to no significant change in the dentin surface, chemical corrosion, or cytotoxicity.

Regulating the Photophysical Property of Organic/Polymer Optical Agents for Promoted Cancer Phototheranostics.

On the basis of the Jablonski diagram, the photophysical properties of optical agents are highly associated with biomedical function and efficacy. Herein, the focus is on organic/polymer optical agents and the recent progress in the main strategies for regulating their photophysical properties to achieve superior cancer diagnosis/phototheranostics applications are highlighted. Both the approaches of nanoengineering and molecular design, which can lead to optimized effectiveness of required biomedical function, are discussed.

Surface-adaptive nanoparticles with near-infrared aggregation-induced emission for image-guided tumor resection.

Aggregation-induced emission (AIE) nanoparticles (NPs) are widely used for image-guided tumor resection because of their high signal-to-noise ratios and long systemic circulation time. These NPs are derived by encapsulating small-molecule fluorescent dyes with AIE property inside the cores of NPs assembled by amphiphilic polymers. Although the systemic circulation of AIE NPs is prolonged, hydrophilic polymer coatings simultaneously decrease the binding and uptake of AIE NPs by tumor cells. To overcome this problem, surface-adaptive AIE dye-encapsulated mixed-shell micelles (MSMs) with polyethylene glycol/poly (ß-amino ester) (PEG/PAE) surfaces were prepared. Due to the charge conversion ability of PAE, MSMs demonstrated enhanced cellular uptake by tumor cells in acidic conditions. In addition, compared with single-PEG-shelled micelles (PEGSMs), MSMs exhibited prolonged systemic circulation due to the presence of micro-phase separated surfaces. Moreover, due to the co-ordination effect of enhanced cancer cell uptake and prolonged systemic circulation time, MSMs were more enriched than PEGSMs in the tumor cells and exhibited excellent performance during image-guided tumor resection.

Surface-adaptive zwitterionic nanoparticles for prolonged blood circulation time and enhanced cellular uptake in tumor cells.

Recently, zwitterionic materials have been developed as alternatives to PEG for prolonging the circulation time of nanoparticles without triggering immune responses. However, zwitterionic coatings also hindered the interactions between nanoparticles and tumor cells, leading to less efficient uptake of nanoparticles by cancer cells. Such effect significantly limited the applications of zwitterionic materials for the purposes of drug delivery and the development to novel therapeutic agents. To overcome these issues, surface-adaptive mixed-shell micelles (MSMs) with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)/poly(ß-amino ester) (PAE) heterogeneous surfaces were constructed. Owing to the synergistic effect of zwitterionic coatings and micro-phase-separated surfaces, PMPC mixed-shell micelles exhibited the improved blood circulation time compared to single-PEG-shell micelles (PEGSMs) and single-PMPC-shell micelles (PMPCSMs). Moreover, such MSMs can convert their surface to positively charged ones in response to the acidic tumor microenvironment, leading to a significant enhancement in cellular uptake of MSMs by tumor cells. This strategy demonstrated a general approach to enhance the cellular uptake of zwitterionic nanoparticles without compromising their long circulating capability, providing a practical method for improving the tumor-targeting efficiency of particulate drug delivery systems. STATEMENT OF SIGNIFICANCE: Herein we demonstrate a general strategy to integrate non-fouling zwitterionic surface on the nanoparticles without compromising their capability of tumor accumulation, by constructing a surface-adaptive mixed-shell micelles (MSMs) with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)/poly(ß-amino ester) (PAE) heterogeneous surfaces. At the blood pH (7.4), PAE chains collapsed to the inner of the shell due to the deprotonation, and the forming micro-phase separation structure was synergistic with zwitterionic surface to prolong the circulation time of MSMs in the blood. While at the tumor sites, PAE was protonated, and the positively charged surface of MSMs enhanced cellular uptake. This self-assembly-based strategy is compatible to other zwitterionic materials, endowing a great flexibility for the construction of responsive drug delivery systems particularly to the novel chemotherapeutic agents.

Silver-Decorated Polymeric Micelles Combined with Curcumin for Enhanced Antibacterial Activity.

Because of the mounting prevalence of complicated infections induced by multidrug-resistant bacteria, it is imperative to develop innovative and efficient antibacterial agents. In this work, we design a novel polymeric micelle for simultaneous decorating of silver nanoparticles and encapsulating of curcumin as a combination strategy to improve the antibacterial efficiency. In the constructed combination system, silver nanoparticles were decorated in the micellar shell because of the in situ reduction of silver ions, which were absorbed by the poly(aspartic acid) (PAsp) chains in the shell. Meanwhile, natural curcumin was encapsulated into the poly(ε-caprolactone) (PCL) core of the micelle through hydrophobic interaction. This strategy could prevent aggregation of silver nanoparticles and improve the water solubility of curcumin at the same time, which showed enhanced antibacterial activity toward Gram-negative P.aeruginosa and Gram-positive S.aureus compared with sliver-decorated micelle and curcumin-loaded micelle alone, due to the cooperative antibacterial effects of the silver nanoparticles and curcumin. Furthermore, the achieved combinational micelles had good biocompatibility and low hemolytic activity. Thus, our study provides a new pathway in the rational design of combination strategy for efficiently preventing the ubiquitous bacterial infections.

A surface-adaptive nanocarrier to prolong circulation time and enhance cellular uptake.

Based on the protonation/deprotonation of poly(ß-amino ester) (PAE), mixed-shell micelles (MSMs) with adaptive surfaces could rapidly and reversibly change surface properties to prolong circulation time in blood (pH 7.4) and enhance cellular uptake at tumor sites (pH 6.5).