A Phototheranostic Strategy to Continuously Deliver Singlet Oxygen in the Dark and Hypoxic Tumor Microenvironment.

Continuous irradiation during photodynamic therapy (PDT) inevitably induces tumor hypoxia, thereby weakening the PDT effect. In PDT-induced hypoxia, providing singlet oxygen from stored chemical energy may enhance the cell-killing effect and boost the therapeutic effect. Herein, we present a phototheranostic (DPPTPE@PEG-Py NPs) prepared by using a 2-pyridone-based diblock polymer (PEG-Py) to encapsulate a semiconducting, heavy-atom-free pyrrolopyrrolidone-tetraphenylethylene (DPPTPE) with high singlet-oxygen-generation ability both in dichloromethane and water. The PEG-Py can trap the 1 O2 generated from DPPTPE under laser irradiation and form a stable intermediate of endoperoxide, which can then release 1 O2 in the dark, hypoxic tumor microenvironment. Furthermore, fluorescence-imaging-guided phototherapy demonstrates that this phototheranostic could completely inhibit tumor growth with the help of laser irradiation.

Bifunctional defect mediated direct Z-scheme g-C3N4-x/Bi2O3-y heterostructures with enhanced piezo-photocatalytic properties for efficient tooth whitening and biofilm eradication.

Biofilm-associated dental diseases and tooth discoloration have recently become the major barriers to achieve healthy teeth. However, there are few effective strategies to address these issues. Herein, the piezo-photocatalytic process is first proposed to be applied for biofilm eradication and tooth whitening with well-designed direct Z scheme g-C3N4-x/Bi2O3-y heterostructures. DFT calculation and XPS results verify the formation of direct Z scheme g-C3N4/Bi2O3 heterostructures theoretically and experimentally. Using the direct Z scheme g-C3N4-x/Bi2O3-y heterostructure, excellent piezo-photocatalytic effects for tooth whitening and biofilm removal are achieved. For piezo-photocatalytic degradation of the typical food colorant of indigo carmine the degradation rate constant is about quadruple that of piezocatalytic and 2.6 times of photocatalytic treatment. Tooth whitening experiments indicate that g-C3N4-x/Bi2O3-y could whiten the stained teeth through the synergistic piezo-photocatalysis. In addition, excellent antibacterial performances can be obtained on the g-C3N4-x/Bi2O3-y heterostructure through piezo-photocatalytic treatment. Not only the planktonic S. mutans but also those bacteria embedded in biofilms can be effectively killed. The analyses of the piezo-photocatalytic mechanism indicates that the enhanced piezo-photocatalytic performance of the g-C3N4-x/Bi2O3-y heterostructure could be attributed to the much higher separation efficiency of photoexcited charge carriers, increased production amounts of ROS and superior adsorption ability for bacteria than those with bare semiconductors of g-C3N4-x and Bi2O3-y and those treated only with ultrasonic vibration or irradiation. Biosafety results show that the g-C3N4-x/Bi2O3-y heterostructure is biologically safe and piezo-photocatalytic treatment has no harm the tooth structure, demonstrating the great potential of piezo-photocatalytic effect based new tooth whitening and antibacterial technology in future dental care fields.

Ultrasound improved immune adjuvant delivery to induce DC maturation and T cell activation.

Tumor immunotherapy has emerged as a promising approach to tumor treatment. Currently, immune adjuvant-based therapeutic modalities are rarely curative in solid tumors owing to challenges including the low permeability and extremely poor water solubility of these adjuvants, limiting their ability to effectively promote dendritic cell (DC) maturation. Herein, we employed ultrasound-mediated cavitation (UMC) to promote the delivery of Toll-like receptor agonist (R837)-loaded pH-responsive liposomes (PEOz-Lip@R837) to tumors. The tumor-associated antigens (TAAs) produced by UMC treatment exhibited vaccinal activity, particularly in the presence of immune adjuvants, together promoting the maturation of DC and inducing cytokine production. Importantly, UMC can down-regulate immune checkpoint molecules, like Cd274, Foxp3 and Ctla4, synergistically stimulating the activation and proliferation of T cells in the body to facilitate tumor treatment. This UMC-enhanced PEOz-Lip@R837 approach was able to induce a robust antitumor immune response capable of arresting primary and distant tumor growth, while also developing immunological memory, protecting against tumor rechallenge following initial tumor clearance. Overall, these results highlight a promising UMC- and pH-sensitive immune adjuvant delivery-based treatment for tumors with the potential for clinical application.

Smart Nanovesicle-Mediated Immunogenic Cell Death through Tumor Microenvironment Modulation for Effective Photodynamic Immunotherapy.

Combination therapy that could better balance immune activation and suppressive signals holds great potential in cancer immunotherapy. Herein, we serendipitously found that the pH-responsive nanovesicles (pRNVs) self-assembled from block copolymer polyethylene glycol-b-cationic polypeptide can not only serve as a nanocarrier but also cause immunogenic cell death (ICD) through preapoptotic exposure of calreticulin. After coencapsulation of a photosensitizer, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) and an indoleamine 2,3-dioxygenase inhibitor, indoximod (IND), pRNVs/HPPH/IND at a single low dose elicited significant antitumor efficacy and abscopal effect following laser irradiation in a B16F10 melanoma tumor model. Treatment efficacy attributes to three key factors: (i) singlet oxygen generation by HPPH-mediated photodynamic therapy (PDT); (ii) increased dendritic cell (DC) recruitment and immune response provocation after ICD induced by pRNVs and PDT; and (iii) tumor microenvironment modulation by IND via enhancing P-S6K phosphorylation for CD8+ T cell development. This study exploited the nanocarrier to induce ICD for the host's immunity activation. The "all-in-one" smart nanovesicles allow the design of multifunctional materials to strengthen cancer immunotherapy efficacy.

A Rationally Designed Semiconducting Polymer Brush for NIR-II Imaging-Guided Light-Triggered Remote Control of CRISPR/Cas9 Genome Editing.

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) genome-editing system has shown great potential in biomedical applications. Although physical approaches, viruses, and some nonviral vectors have been employed for CRISPR/Cas9 delivery and induce some promising genome-editing efficacy, precise genome editing remains challenging and has not been reported yet. Herein, second near-infrared window (NIR-II) imaging-guided NIR-light-triggered remote control of the CRISPR/Cas9 genome-editing strategy is reported based on a rationally designed semiconducting polymer brush (SPPF). SPPF can not only be a vector to deliver CRISPR/Cas9 cassettes but also controls the endolysosomal escape and payloads release through photothermal conversion under laser irradiation. Upon laser exposure, the nanocomplex of SPPF and CRISPR/Cas9 cassettes induces effective site-specific precise genome editing both in vitro and in vivo with minimal toxicity. Besides, NIR-II imaging based on SPPF can also be applied to monitor the in vivo distribution of the genome-editing system and guide laser irradiation in real time. Thus, this study offers a typical paradigm for NIR-II imaging-guided NIR-light-triggered remote control of the CRISPR/Cas9 system for precise genome editing. This strategy may open an avenue for CRISPR/Cas9 genome-editing-based precise gene therapy in the near future.

Water-soluble clickable nucleic acid (CNA) polymer synthesis by functionalizing the pendant hydroxyl.

Synthetic biomacromolecules that mimic natural polymeric structures are of significant interest. For most applications of these materials, however, aqueous solubility is a necessity. Here, we present the synthesis of an intrinsically water soluble single stranded DNA analog formed by the synthesis of a Clickable Nucleic Acid (CNA). These molecules are formed with pendant hydroxyl groups present on the main polymer backbone, and subsequent modification of those hydroxyls with sulfonate moieties further enhances the hydrophilicity of these molecules.

Chirality-Discriminated Conductivity of Metal-Amino Acid Biocoordination Polymer Nanowires.

Biocoordination polymer (BCP) nanowires are successfully constructed through self-assembly of chiral cysteine amino acids and Cd cations in solution. The varied chirality of cysteine is explored to demonstrate the difference of BCP nanowires in both morphology and structure. More interestingly and surprisingly, the electrical property measurement reveals that, although all Cd(II)/cysteine BCP nanowires behave as semiconductors, the conductivity of the Cd(II)/dl-cysteine nanowires is 4 times higher than that of the Cd(II)/l-cysteine or Cd(II)/d-cysteine ones. The origin of such chirality-discriminated characteristics registered in BCP nanowires is further elucidated by theoretical calculation. These findings demonstrate that the morphology, structure, and property of BCP nanostructures could be tuned by the chirality of the bridging ligands, which will shed light on the comprehension of chirality transcription as well as construction of chirality-regulated functional materials.

Core-Shell Upconversion Nanoparticle@Metal-Organic Framework Nanoprobes for Luminescent/Magnetic Dual-Mode Targeted Imaging.

Core-shell upconversion nanoparticle@metal-organic framework (UCNP@MOF) nanostructures are constructed by coating hexagonal NaYF4 :Yb,Er nanoparticle (NP) cores with amino-functionalized iron carboxylate MOF shells. These nanostructures combine the near-infrared optical property of the UCNP cores and the T2 -magnetic response (MR) imaging property of the MOF shells. After surface modification, the core-shell nanostructures are demonstrated as high-resolution nanoprobes for targeted luminescence/MR imaging both in vitro and in vivo.

Three-dimensional graphene/metal oxide nanoparticle hybrids for high-performance capacitive deionization of saline water.

A novel and general method is proposed to construct three-dimensional graphene/metal oxide nanoparticle hybrids. For the first time, it is demonstrated that this graphene-based composite with open pore structures can be used as the high-performance capacitive deionization (CDI) electrode materials, which outperform currently reported materials. This work will offer a promising way to develop highly effective CDI electrode materials.