Guo-Bin Qi

In Situ Formation of Nanofibers from Purpurin18‐Peptide Conjugates and the Assembly Induced Retention Effect in Tumor Sites

An assembly-induced retention effect for enhanced tumor photoacoustic (PA) imaging and therapeutics is described. A responsive small-molecule precursor is prepared that simultaneously self-assembles into nanofibers in tumor sites that exhibit an assembly-induced retention effect, which results in an improved PA imaging signal and enhanced therapeutic efficacy. This successful proof-of-concept study paves the way to develop novel supramolecular biomaterials for cancer diagnostics and therapeutics.

Vancomycin-Modified Mesoporous Silica Nanoparticles for Selective Recognition and Killing of Pathogenic Gram-Positive Bacteria Over Macrophage-Like Cells

Rapid, reliable recognition and detection of bacteria from an authentic specimen have been gained increasing interests in the past decades. Various materials have been designed and prepared for implementation of bacterial recognition and treatment in the artificial systems. However, in the complicated physiological condition, the macrophages always compromise the outcomes of bacterial detection and/or treatment. In this work, we demonstrated the vancomycin-modified mesoporous silica nanoparticles (MSNs is a subset of Van) for efficiently targeting and killing gram-positive bacteria over macrophage-like cells. Owing to the specific hydrogen bonding interactions of vancomycin toward the terminal d-alanyl-d-alanine moieties of gram-positive bacteria, the MSNs is a subset of Van exhibited enhanced recognition for gram-positive bacteria due to the multivalent hydrogen binding effect. Furthermore, the fluorescent molecules (FITC) were covalently decorated inside of mesopores of MSNs for tracking and visualizing the MSNs is a subset of Van during the detection/treatment processes. Upon incubation of FITC decorated MSNs with bacteria (i.e., S. aureus and E. coli as gram-positive and gram-negative bacteria, respectively) or macrophage-like cells (Raw 264.7), the fluorescence signals in S. aureus were 2-4 times higher than that in E. coli and no detectable fluorescence signals were observed in Raw 264.7 cells under the same condition. Finally, the MSNs is a subset of Van showed unambiguous antibacterial efficacy without decrease in cell viability of macrophage-like cells. This new strategy opens a new door for specific detection and treatment of pathogenic bacteria with minimized side effects.

A Peptide‐Network Weaved Nanoplatform with Tumor Microenvironment Responsiveness and Deep Tissue Penetration Capability for Cancer Therapy

Novel core-shell tumor-penetrating vesicles consisting of a nanovesicle core with tumor-penetrating ligands and enzymatically degradable polymeric peptides anchored covalently to the core to form a thin polymeric shell are evaluated as drug-delivery systems. This delivery platform demonstrates an enhanced therapeutic efficacy attributed to the synergistic contributions from matrix metalloproteinase (MMP)-responsive drug release as well as improved tumor accumulation and penetration in the tumor microenvironment.

Pathological‐Condition‐Driven Construction of Supramolecular Nanoassemblies for Bacterial Infection Detection

A pyropheophorbide-α-based building block (Ppa-PLGVRG-Van) can be used to construct self-aggregated superstructures in vivo for highly specific and sensitive diagnosis of bacterial infection by noninvasive photoacoustic tomography. This in vivo supramolecular chemistry approach opens a new avenue for efficient, rapid, and early-stage disease diagnosis with high sensitivity and specificity.

An adaptive biointerface from self-assembled functional peptides for tissue engineering.

A self-assembled peptide-based biointerface is demonstrated with triple functional layers that can significantly improve the tissue self-healing process or prevent biofilm-mediated chronic inflammation. This smart biointerface is composed of three functional moieties (i.e., a cell-adhesive peptide, an infectious environment-responsive peptide, and an antifouling hexaethylene glycol (HEG) layer), and the resulting interface coated onto prosthetic replacements can smartly respond to the surrounding physiological or pathological microenvironment.

Dynamic disordering of liposomal cocktails and the spatio-temporal favorable release of cargoes to circumvent drug resistance

Multidrug resistance (MDR) has been a major impediment to the success of cancer chemotherapy. Extensive efforts have been devoted to the development of drug delivery systems using nanotechnology to reverse MDR in cancer. However, the spontaneous release of drug payloads was always a slow process, which leads to the low intracellular drug concentration resulting in consequent drug insensitivity. To circumvent this limitation, we described a liposomal cocktail (LMDHV) constructed by a pH-responsive molecule (i.e., malachite green carbinol base (MG)) and liposome conjugated with Her-2 antibody for codelivery of doxorubicin (DOX) and verapamil (VER) to suppress drug resistance in Her-2 positive breast cancer. MG inserted in the bilayer as pH responders greatly contributed to the destabilization of the vesicle membrane in low pH, followed by the rapid release of the payloads. LMDHV showed 6-fold reversal efficiency in DOX resistant breast cancer owing to the efficient tumor targeting delivery and rapid burst release of drug intracellularly. Compared to tumor inhibition ratio of treated groups by free DOX (32.4 ± 7.4%), our designed kinetically favorable drug release system exhibited significantly (P < 0.01) enhanced tumor inhibition ratio up to 83.9 ± 12.5%, which is attributed to the remarkably increased drug concentration in cells. The spatio-temporal favorable release of drugs resulted in synergistic inhibition of tumor growth in xenografts. We envision that this new type of liposomal cocktail might be potentially utilized to circumvent drug resistance in the future.

Transformable Nanomaterials as an Artificial Extracellular Matrix for Inhibiting Tumor Invasion and Metastasis

Tumor metastasis is one of the big challenges in cancer treatment and is often associated with high patient mortality. Until now, there is an agreement that tumor invasion and metastasis are related to degradation of extracellular matrix (ECM) by enzymes. Inspired by the formation of natural ECM and the in situ self-assembly strategy developed in our group, herein, we in situ constructed an artificial extracellular matrix (AECM) based on transformable Laminin (LN)-mimic peptide 1 (BP-KLVFFK-GGDGR-YIGSR) for inhibition of tumor invasion and metastasis. The peptide 1 was composed of three modules including (i) the hydrophobic bis-pyrene (BP) unit for forming and tracing nanoparticles; (ii) the KLVFF peptide motif that was inclined to form and stabilize fibrous structures through intermolecular hydrogen bonds; and (iii) the Y-type RGD-YIGSR motif, derived from LN conserved sequence, served as ligands to bind cancer cell surfaces. The peptide 1 formed nanoparticles (1-NPs) by the rapid precipitation method, owing to strong hydrophobic interactions of BP. Upon intravenous injection, 1-NPs effectively accumulated in the tumor site due to the enhanced permeability and retention (EPR) effect and/or targeting capability of RGD-YIGSR. The accumulated 1-NPs simultaneously transformed into nanofibers (1-NFs) around the solid tumor and further entwined to form AECM upon binding to receptors on the tumor cell surfaces. The AECM stably existed in the primary tumor site over 72 h, which consequently resulted in efficiently inhibiting the lung metastasis in breast and melanoma tumor models. The inhibition rates in two tumor models were 82.3% and 50.0%, respectively. This in vivo self-assembly strategy could be widely utilized to design effective drug-free biomaterials for inhibiting the tumor invasion and metastasis.

Surface charge-conversion polymeric nanoparticles for photodynamic treatment of urinary tract bacterial infections

Urinary tract infections are typical bacterial infections which result in a number of economic burdens. With increasing antibiotic resistance, it is urgent that new approaches are explored that can eliminate pathogenic bacteria without inducing drug resistance. Antimicrobial photodynamic therapy (PDT) is a new promising tactic. It is a gentle in situ photochemical reaction in which a photosensitizer (PS) generates reactive oxygen species (ROS) under laser irradiation. In this work, we have demonstrated Chlorin e6 (Ce6) encapsulated charge-conversion polymeric nanoparticles (NPs) for efficiently targeting and killing pathogenic bacteria in a weakly acidic urinary tract infection environment. Owing to the surface charge conversion of NPs in an acidic environment, the NPs exhibited enhanced recognition for Gram-positive (ex. S. aureus) and Gram-negative (ex. E. coli) bacteria due to the charge interaction. Also, those NPs showed significant antibacterial efficacy in vitro with low cytotoxicity. The MIC value of NPs to E. coli is 17.91 μg ml(-1), compared with the free Ce6 value of 29.85 μg ml(-1). Finally, a mouse acute cystitis model was used to assess the photodynamic therapy effects in urinary tract infections. A significant decline (P < 0.05) in bacterial cells between NPs and free Ce6 occurred in urine after photodynamic therapy treatment. And the plated counting results revealed a remarkable bacterial cells drop (P < 0.05) in the sacrificed bladder tissue. Above all, this nanotechnology strategy opens a new door for the treatment of urinary tract infections with minimal side effects.

In Situ Construction and Characterization of Chlorin-Based Supramolecular Aggregates in Tumor Cells

We demonstrate in situ construction and characterization of supramolecular aggregates from chlorin p6 (Cp6) molecules in tumor cells. Fully deprotonated Cp6 molecules in neutral condition were partially protonated inside the acidic lysosomes of cells and significantly increased the hydrophobicity of them that resulted in simultaneous formation of J-type aggregates. Importantly, the formation of J-aggregates was fully characterized in artificial tissues by UV-vis, circular dichroism (CD) and transmission electron microscope (TEM) techniques. Compared to the monomers, the J-aggregates exhibited 55-fold enhanced thermal conversion efficiency (η) at the optimal excitation wavelength (690 nm). The remarkably increased heat effect contributed to the stronger photoacoustic (PA) signals, leading to at least 2 orders of magnitude increase of the tumor-to-normal tissue ratio (T/N), which was defined as the PA signal ratio between tumor site and surrounding normal tissue. We envision that this proof-of-concept study will open a new way to develop tumor environment-induced self-assembly for variable biomedical applications.

Photoacoustic Imaging: In Situ Formation of Nanofibers from Purpurin18‐Peptide Conjugates and the Assembly Induced Retention Effect in Tumor Sites (Adv. Mater. 40/2015)

As described on page 6125, H. Wang and co-workers design a small molecule that simultaneously self-assembles into nanofibers in tumor sites and exhibits an assembly-induced retention (AIR) effect, which results in an improved photoacoustic (PA) imaging signal and enhanced therapeutic efficacy. It is envisaged that the AIR effect based on the assembly of supramolecular structures in living systems will pave the way to develop novel functional nanomaterials for cancer diagnostics and therapeutics.