Construction of biocompatible bovine serum albumin nanoparticles composed of nano graphene oxide and AIEgen for dual-mode phototherapy bacteriostatic and bacterial tracking.

BACKGROUND: Efficient and highly controllable antibacterial effect, as well as good biocompatibility are required for antibacterial materials to overcome multi-drug resistance in bacteria. Herein, nano graphene oxide (NGO)-based near-infrared (NIR) photothermal antibacterial materials was schemed to complex with biocompatible bovine serum albumin (BSA) and aggregation-induced emission fluorogen (AIEgen) with daylight-stimulated ROS-producing property for dual-mode phototherapy in the treatment of antibiotic resistance bacteria. RESULTS: Upon co-irradiation of daylight and NIR laser, NGO-BSA-AIE nanoparticles (NPs) showed superiorly antibacterial effect (more than 99%) both against amoxicillin (AMO)-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by comparison with sing-model phototherapy. Meanwhile, the NGO-BSA-AIE NPs displayed prominent stability and excellently controllable biocompatibility. More importantly, under daylight irradiation, the AIEgen not only produced plentiful ROS for killing bacteria, but also presented fluorescence image for tracking bacteria. CONCLUSIONS: Hence, the designed system provided tempting strategy of employing light as impetus for tracking bacterial distribution and photothermal/photodynamic synergistic treatment of antibiotic resistance antibacterial.

Polyplex Micelle with pH-Responsive PEG Detachment and Functional Tetraphenylene Incorporation to Promote Systemic Gene Expression.

Tetraphenylene (TPE), characterized as a lipophilic and aggregation-induced-emissive fluorophore, was used to incorporate into an electrostatic self-assembled polyethylenimine-poly(ethylene glycol) (PEI-PEG)/plasmid DNA (pDNA) complexed micelle. The hydrophobic character of TPE appeared to drive a higher degree of condensation of the pDNA payload, which consequently resulted in not only strengthened colloidal stability of the constructed polyplex micelle but also improved biocompatibility by virtue of the elevated PEG crowdedness owing to the TPE-induced collapse of pDNA. These beneficial consequences potentially permitted a larger number of polyplex micelles to be internalized into the cells. PEG segments were designed to enable selective detachment from polyplex micelles in acidic milieu, e.g., the tumor microenvironment, and intracellular endosome compartment, based on the strategic arrangement of acid-responsive cleavable linkage between PEG and PEI. Upon PEG detachment, the exposure of cationic PEI/TPE polyplex was allowed to directly interact with the cell membrane, endosome membrane, and charged intracellular species, thus promoting cell internalization, endosome escape, and the release of the pDNA payload. Of note, this association of cationic PEI/TPE polyplex with the endosomal membrane could be further facilitated with the aid of lipophilic TPE, thereby eliciting pronounced destabilization potency to the endosome membrane and exerting an endosomal escape function. Eventually, the proposed system of these facile strategies, including responsive PEG detachment and functional TPE incorporation, was proven to provide efficient gene expression in the targeted tumors with an appreciable safety profile via systemic administration.

Construction of traceable cucurbit[7]uril-based virus-mimicking quaternary complexes with aggregation-induced emission for efficient gene transfection.

Construction of an efficient cationic gene delivery system with low cytotoxicity, high transfection efficacy, as well as gene tracking function remains a major challenge in gene therapy. Fabrication of simple and reversible nanocomplexes based on host-guest interaction provides an opportunity to construct stimuli-responsive intelligent supramolecular systems. Inspired by the hierarchical structure of viruses, a novel virus-mimicking PG/CB/TPE/DNA gene delivery system is developed via a multistep noncovalent self-assembly process between pDNA and the preformed PG/CB/TPE complexes based on the host-guest interaction between cucurbit[7]uril (CB[7]) and the protonated diamine group in the poly(glycidyl methacrylate)s derivative (PG), as well as the electrostatic interaction between para-carboxyl functionalized tetraphenylethylene (TPE) and cationic PG. The developed efficient multifunctional gene delivery system exhibits stimuli responsive characteristics and aggregation-induced emission phenomena, thereby enabling gene delivery pH responsiveness and traceability. Moreover, the introduction of TPE and CB[7] endows the self-assembled PG/CB/TPE/DNA complexes with virus-mimicking architecture and properties such as low cytotoxicity, high stability, excellent endosomal escape, and efficient transfection, which are expected to be used as a promising gene delivery system.

Reactive Oxygen Species Self-Sufficient Multifunctional Nanoplatform for Synergistic Chemo-Photodynamic Therapy with Red/Near-Infrared Dual-Imaging.

Developing multifunctional nanoplatforms that combine controlled drug release, therapy, and real-time monitoring of intracellular distribution of therapeutic agents can provide a solution for practical precision cancer therapy. Herein, a daylight activatable and red to near-infrared (NIR) dual-imaging guided multifunctional anticancer nanoplatform based on diselenium-conjugated and aggregation-induced emission fluorogen (AIEgen)-cross-linked oligoethylenimine polymer loaded with cisplatin (Pt) and biscyclometalated iridium(III) (Ir(III)) complex (Pt&Ir@P NPs) is reported. Upon short-time daylight irradiation, the nanoplatform generates reactive oxygen species (ROS), which help them to escape from endo/lysosomes via enhanced lysosomal membrane permeability. Meanwhile, the chemotherapeutic drug cisplatin and the photosensitizer (PS) Ir(III) complex are released via breaking the ROS-labile diselenium bond. The released PS, together with AIEgen, respond to the continuous long-time daylight irradiation and produce more ROS, inducing photodynamic therapy (PDT) and damaging the nucleus. Along with PDT, selenium liberates cisplatin and exerts chemotherapy in the presence of endogenous spermine. In addition, the red/NIR emitting Ir(III) complex and the engineered AIEgen act as dual-imaging agents for real-time monitoring the distribution of PS and polymer. This daylight responsive multifunctional nanoplatform for efficient anticancer therapy and imaging could provide an intriguing strategy for developing theranostic antitumor platforms.

A cyanine-based polymeric nanoplatform with microenvironment-driven cascaded responsiveness for imaging-guided chemo-photothermal combination anticancer therapy.

Finding out how to overcome multistage biological barriers for nanocarriers in cancer therapy to obtain highly precise drug delivery is still a challenge. Herein, we prepared a multistage and cascaded switchable polymeric nanovehicle, self-assembled from polyethylene glycol grafted amphiphilic copolymer containing hydrophobic poly(ortho ester) and hydrophilic ethylenediamine-modified poly(glycidyl methacrylate) (PEG-g-p(GEDA-co-DMDEA)) for imaging-guided chemo-photothermal combination anticancer therapy. Notably, a novel ATRP initiator containing cyanine dye was designed and attached to the polymer, providing the nanovehicle with NIR-light induced photothermal and fluorescent properties. The PEG shell displayed tumor-microenvironment-induced detachment, resulting in the surface charge change of the nanovehicle from neutral to positive and thus enhancing cellular uptake. Subsequently, the hydrophobic pDMDEA hydrolyzed into a hydrophilic segment in the acidic lysosome, leading to sufficient drug release. Finally, with the aid of the photothermal property, the therapeutic drug DOX successfully escaped from the lysosome to exert chemotherapy. This well-defined polymeric nanoplatform promoted the development of designing novel theranostic polymeric nanovehicles for precise cancer therapy.

A theranostic saponin nano-assembly based on FRET of an aggregation-induced emission photosensitizer and photon up-conversion nanoparticles.

A photodynamic aggregation-induced emissive (AIE) fluorophore, characterized by near-infrared (NIR) emission, was created based on a fluorescence resonance energy transfer (FRET) donor of appreciable NIR up-conversion nanoparticles (UCNPs) and acceptor of immense fluorescence emissive AIEgen. Hence, the entrapment of the FRET couple into an amphiphilic saponin-based nanoscaled self-assembly demonstrated appealing theranostic functions in producing immense fluorescence emission and cytotoxic reactive oxygen species (ROS).

Construction of Bovine Serum Albumin/AIE-Based Quaternary Complexes for Efficient Gene Transfection.

High transfection efficiency and superior cell imaging are required for cationic polymers-based gene delivery system to afford high therapeutic effect but its high toxicity and unstable cell imaging are easily ignored. In this study, cationic amino poly(glycerol methacrylate) derivative (PGMA-EDA) is used to incorporate bovine serum albumin (BSA) and aggregation-induced emission (AIE) molecular (tetraphenylethylene derivatives, TPE) as an efficient carrier for gene transfection and intracellular imaging. The obtained polymer/pDNA-TPE/BSA (PDTB) quaternary nanoparticles (NPs) not only exhibit efficient gene transfection but also show excellent biocompatibility. After inclusion of TPE/BSA (TB) NPs, BSA promoted dissociation of the complexes upon being protonated and the lipophilic TPE-reduced endosomal membrane stability, which enhanced endosomal escape of pDNA payload, finally resulting in an excellent gene transfection. On the other hand, less positive surface charge of PDTB NPs than that of the binary PD complexes, as well as the addition of biocompatible BSA, both factors contribute to the improved cell viability. Moreover, the AIE feature of TPE compared to aggregation-caused quenching character of conventional fluorophores enables the complex with stably tracking the delivery of pDNA into cancer cells. Therefore, the newly developed PDTB complexes may be a promising candidate vector for traceable, safe, and effective gene delivery.

Hyaluronic acid/PEGylated amphiphilic nanoparticles for pursuit of selective intracellular doxorubicin release.

Polyethylene glycol (PEG)-lyted cationic amphiphilic copolymers were employed as complexing agents with biocompatible anionic hyaluronic acid (HA) for the controlled release of doxorubicin (DOX). The overexpressed receptors to HA in a variety of cancerous cells enable preferential endocytosis of the HA-functionalized nanoparticles. Moreover, introduction of HA is supposed to diminish the unfavorable non-specific reactions in the biological milieu. Particularly, the drastic positive charge was validated post-endocytosis as a consequence of our strategic molecular design for the promotion of positive charges of cationic components. This deshielding effect of the anionic hyaluronic acid by endogenous hyaluronidase in endosomes and demotion of PEG at the endosome acid microenvironment consequently results in the structural rearrangement and favorable reaction of the resulting positive-charged structure with the intracellular species and structures, ultimately giving rise to liberation of the doxorubicin for the subsequent molecular pharmaceutic consequences. Simultaneously, the system containing quaternary ammonium salt and hydrophobic n-octyl acrylate (OA) possesses considerable antibacterial ability to alleviate anti-cancer drugs resistance. This delivery system is intended to overcome the intratumor bacteria-induced tumor resistance.

Aggregation-Induced-Emissive Molecule Incorporated into Polymeric Nanoparticulate as FRET Donor for Observing Doxorubicin Delivery.

Tetraphenylethene (TPE) derivatives characterized with distinct aggregation-induced-emission, attempted to aggregate with doxorubicin (Dox) to formulate the interior compartment of polymeric nanoparticulate, served as fluorescence resonance energy transfer (FRET) donor to promote emission of acceptor Dox. Accordingly, this FRET formulation allowed identification of Dox in complexed form by detecting FRET. Important insight into the Dox releasing can be subsequently explored by extracting complexed Dox (FRET) from the overall Dox via direct single-photon excitation of Dox. Of note, functional catiomers were used to complex with FRET partners for a template formulation, which was verified to induce pH-responsive release in the targeted subcellular compartment. Hence, this well-defined multifunctional system entitles in situ observation of the drug releasing profile and insight on drug delivery journey from the tip of injection vein to the subcellular organelle of the targeted cells.