Pei-Pei Yang

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.

Host Materials Transformable in Tumor Microenvironment for Homing Theranostics

A pathology-adaptive nanosystem, in which nest-like hosts are built based on nanofibers that are transformed from i.v. injected nanoparticles under the acidic tumor microenvironment. The solid tumor is artificially modified by nest-like hosts readily and firmly, resulting in highly efficient accumulation and stabilization of guest theranostics. This strategy shows great potential for the theranostics delivery to tumors.

Reorganization of self-assembled supramolecular materials controlled by hydrogen bonding and hydrophilic–lipophilic balance

Supramolecular assembly to form a large variety of nanostructures has received increasing attention for diverse applications, in particular biomedical applications involving drug delivery, bioimaging, therapy and regenerative medicine. Meanwhile, the modulation of morphology and structure of nanoassemblies is a still big challenge. Herein, we report a series of supramolecular structures (BP-KLVFFG-PEG, BKP) and elucidate that their morphological transformation process is modulated by H-bonding, π-π interactions and hydrophilic/lipophilic balance (HLB). Our studies reveal that the hydrophobic and π-π interactions initially drive the self-assembly of BKP into nanoparticles in J-type aggregates in water, and the H-bonding interactions further induce an in situ spontaneous morphology transformation into nanofibers. The conversion rate is related to the length of the hydrophilic chains. The nanofibers are maintained by β-sheet H-bonds with parallel structure. Our results provide insight into the relationship between molecular structures and morphological transformations of self-assembled nanomaterials, which will guide the design of complex self-assembled materials in biological conditions.

Bis-pyrene based reversibly multi-responsive fluorescence switches

A bis-pyrene derivative m-Py-BP was designed and synthesized, where two pyrenes units were connected by pyridine-2,6-dicarbonyl linkers, displaying multi-responsive fluorescence switching behaviors. In solution, the quenched fluorescence emission of m-Py-BP by HCl was recovered with the addition of NH3·H2O. In the solid state, m-Py-BP exhibited vapor, mechano and thermo-induced fluorescence variations. The as-prepared sample showed green fluorescence (G form) with emission maxima at 483 nm. Upon mechanical shearing, the fluorescence of G form was transformed into a yellow color (Y form) by disrupting the crystalline structures. Vapor or heating induced the transformation from Y to G form. Powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), time-resolved fluorescence (TRF) and scanning electron microscopy (SEM) supported the corresponding changes in supramolecular structures and morphologies. Interestingly, m-Py-BP showed acid–base responsive fluorescence switching behavior. The HCl could quench the fluorescence of Y form to DY (dark yellow) form, which could be recovered to Y form in the presence of NH3·H2O or converted to DG (dark green) form upon treatment with CHCl3 solvent vapor. Furthermore, the DG form could become DY form by mechanical shearing or convert to G form upon treatment with NH3·H2O vapor. The halochromic fluorescence should be related to the protonation of m-Py-BP molecules by acid treatment. The protonated pyridine became a strong electron acceptor, resulting in fluorescence quenching. m-Py-BP could construct a multi-responsive and recyclable fluorescence switching system.

Photothermal Ring Integrated Intraocular Lens for High-Efficient Eye Disease Treatment.

Posterior capsule opacification (PCO) is the most common complication after cataract surgery. So far, the only method for PCO treatment is the precisely focused laser surgery. However, it causes severe complications such as physical damages and neuron impairments. Here, a nanostructured photothermal ring integrated intraocular lens (Nano-IOLs) is reported, in which the rim of commercially available IOLs (C-IOLs) is decorated with silica coated Au nanorods (Au@SiO2 ), for high-efficient prevention of PCO after cataract surgery. The Nano-IOLs is capable of eliminating the residual lens epithelial cells (LECs) around Nano-IOLs under mild laser treatment and block the formation of disordered LECs fibrosis, which eventually leads to the loss of vision. The Nano-IOLs shows good biocompatibility as well as extraordinary region-confined photothermal effect. In vivo studies reveal that PCO occurrence in rabbit models is about 30%-40% by using Nano-IOLs, which is significantly lower than the control group that treated with C-IOLs (100% PCO occurrence) 30 d postsurgery. To the best of our knowledge, it is the first example to integrate nanotechnology with intraocular implants aiming to clinically relevant PCO. Our findings indicate that spatial controllability of photothermal effect from nanomaterials may provide a unique way to intervene the PCO-induced loss of vision.

In vivo self-assembly induced retention of gold nanoparticles for enhanced photothermal tumor treatment

We present a simple route to fabricate peptide modified spherical gold nanoparticles (AuNPs@Pep1/Pep2) with enhanced retention performance in tumor sites for improved photothermal treatment (PTT), which was achieved through its in vivo self-assembly triggered by matrix metalloproteinase-2 (MMP-2).

In situ construction of nanonetworks from transformable nanoparticles for anti-angiogenic therapy

Tumor metastasis as the most common reason of death from cancer has always been a great challenge in both clinical and scientific research, where angiogenesis plays a necessary role. Herein, we report an extracellularly transformable nanomaterial for in situ construction of defensive networks on interaction with vascular endothelial growth factor (VEGF) for anti-angiogenic therapy of tumor. The fibrous networks exhibit transformation-enhanced accumulation and retention (TEAR) effects (over 72 h), and bind and intercept cell-secreted VEGF over particulate and molecular anti-angiogenic agents with high efficiency, leading to anti-angiogenesis. This study demonstrates that angiogenesis is positively related to tumor growth as well as tumor metastasis; the anti-angiogenic therapy inhibits tumor metastasis with an inhibition rate of 65.9%. In addition, this extracellular strategy of transformation may be utilized to bind huge amounts of cell-secreted biomolecules/factors or receptors on cell surfaces and inhibit their functionalities for cancer therapy.

Self‐Assembled Fluorescent Organic Nanomaterials for Biomedical Imaging

Fluorescent nanomaterials, self-assembled from building blocks through multiple intermolecular interactions show diversified structures and functionalities, and are potential fluorescence contrast agents/probes for high-performance biomedical imaging. Self-assembled nanomaterials exhibit high stability, long circulation time, and targeted biological distribution. This review summarizes recent advances of self-assembled nanomaterials as fluorescence contrast agents/probes for biomedical imaging. The self-assembled nanomaterials are classified into two groups, i.e., ex situ and in situ construction of self-assembled nanomaterials. The advantages of ex situ as well as in situ constructed nanomaterials for biomedical applications are discussed thoroughly. The directions of future developments for self-assembled nanomaterials are provided.