A special issue focusing on CAS key laboratory of nano-bio interface at Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO)

Nano-bio interface plays a key role in the interactions of nanomaterials and biosystems. The deep understanding of the mechanisms of nano-bio interactions on the nano-bio interface and further optimization of the nano-bio interactions will greatly advance the applications of nanotechnology in life science. The Suzhou Institute of Nano-tech and Nano-bionics (SINANO), Chinese Academy of Sciences (CAS) is one of the national research organizations focusing on nanotechnology research in China. The CAS Key Laboratory of Nano-Bio Interface at SINANO was founded in 2014. The aims and objectives of the Laboratory are studying the major scientific challenges of the nano-bio interfaces between nanomaterials and biosystems and developing novel strategies for interpreting and optimizing the interactions between them, and consequently advancing the applications of nanotechnology in life science. The Laboratory includes three main directions: nano-bio interface design and regulation, in vivo imaging nanotechnologies, and stem cell nanobiotechnologies. This special issue collects the latest research progresses of the Laboratory, including a series of reviews and research articles on the above three topics.

The rational design of nano-bio interface is a prerequisite for effective regulation of the interactions of nanomaterials and biosystems, which is essential in many fields including biosensing, diagnosis, selective targeting and so forth. To achieve the specific recognition between nanomaterials and biological entities, the target molecules such as aptamer and peptide, are generally needed. Prof. Renjun Pei's group in CAS Key Laboratory of Nano-Bio Interface focuses on the screening of aptamers for targeting specific biomolecules or cells. And the aptamers have been successfully used to design various nanocarriers for target delivery. For example, to enhance the regulation efficiency of the target gene and reduce the off-target-mediated side effects of siRNA, the targeting AS1411 aptamer, which could recognize and bind to nucleolin protein overexpressed in cancer cells, was modified on the erythrocyte membrane-camouflaged cationic nanoparticles (NPs@apt). The NPs@apt loaded PD-L1 siRNA and increased its stability, and could be specifically delivered to human non-small-cell lung carcinoma A549 cells and trigger robust gene silencing of PD-L1 with the help of AS1411 aptamer [1]. Moreover, modification of nanomaterials with small molecules or peptides could further endow various functions. The 5β-cholanic acid-modified glycol chitosan-modified poly (d, l-lactic-co-glycolic acid) NPs (PLGA NPs) exhibited significantly higher cellular uptake level of Caco-2 cells than glycol chitosan-coated PLGA NPs due to the aggregation effect mediated by 5β-cholanic acid [2]. Poly-peptide composite systems consisting of various peptides showed multi-dimensional functions. A poly-peptide drug loading system (called HKMA) was constructed of poly-peptide HCBP1 (LGCFPEGEMACWWSGGSGK), KLA (KLAKLAKKLAKLAK), matrix metalloproteinase-2-cleavable peptide (PLGLAG), and albumin-binding domain from N-terminal to C-terminal. Due to the different functionalities of four peptides, the HKMA could specifically respond to the tumor microenvironment and targetedly kill the cancer stem cells [3].

Besides these modified nanomaterial-based precise drug delivery platforms, cell-based biomimetic delivery strategies, including cell-derived membrane and exosome coating methods, and engineered cell strategies have attracted rising attention due to their excellent biological functions and biocompatibilities. Therefore, in this special issue, recent advances in oncologic drug delivery strategies based on T cells, NK cells, macrophages, and some other immune cells were also summarized and reviewed [4]. In solid tumor treatment, these immune cells were directly applied as drug cargos after chemical modification or NP loading, or provided exosomes as nanoscale drug delivery carriers.

Bioimaging has emerged as a critical strategy in disease diagnosis for its capability of monitoring various physiological and pathological information. Interpreting and optimizing the interactions between nanomaterials and biomakers of diseases will aid the development of probes with high sensitivity and specificity. In the past decade, Prof. Qiangbin Wang's group in CAS Key Laboratory of Nano-Bio Interface focuses on the probes and biomedical applications of fluorescence imaging in the second near-infrared window (NIR-II, 1000 − 1700 nm). They reported the first NIR-II quantum dots (Ag₂S QDs), developed various NIR-II imaging instruments, and established a series of fluorescence imaging techniques for oncology and regenerative medicine research [5, 6]. Due to the significantly reduced absorption and scattering effects of NIR-II light in tissues, the novel NIR-II imaging technique has shown superior performance in in vivo bioimaging in terms of the significantly improved penetration depth and spatiotemporal resolution compared with fluorescence imaging in traditional region (400–950 nm). More recently, his group developed several NIR-II ratiometric probes [7], which can further eliminate the interference factors and background noise by presenting a self-calibration reference into a responsive probe. In this special issue, Huang et al summarized the design of NIR ratiometric probes and their applications in intravital biomedical imaging, including molecular detection, drug delivery monitoring, treatment evaluation and etc [8]. Especially, they highlighted the current progresses of NIR-II ratiometric probes and prospected the applications of ratiometric probes in basic research and clinical translation.

Stem cell-based therapy has become the hope for various diseases by replacing and/or regenerating damaged or diseased tissues. In the research field of stem cells nanobiotechnologies in the CAS Key Laboratory of Nano-Bio Interface, various nanomaterials and three-dimensional functionalized scaffolds have been designed to regulate the interactions between nanomaterials and stem cells in their interface, and thereby modulate the function and fate of stem cells to promote tissue regeneration.

Directed differentiation of stem cells is the key to their therapeutic functions. Developing nanotechnological strategies to regulate stem cell differentiation efficiently and specifically is critical for the success of cellular therapeutics. In this special issue, Cao et al developed a novel linear-branched poly(β-amino esters) (called STBD) nanocarrier with multiple positively charged amine terminus and degradable intermolecular ester bonds for efficient gene loading and delivery, and effective gene release and transcription in neural stem cells (NSCs). Thereby, the levels of neuronal differentiation and maturation of NSCs were significantly enhanced after delivering siRNA (shSOX9) expression plasmid into NSCs for silencing the SOX9 gene in NSCs by the STBD nanocarrier [9]. The STBD/deoxyribonucleic acid nano-polyplex may serve as a powerful non-viral approach for gene delivery in NSCs, showing broad application prospects in NSC-based regenerative medicine.

Three-dimensional functionalized scaffolds that can mimic tissue properties to construct microenvironments for cell fate modulation have shown great potential in regenerative medicine. To build a favorable matrix for NSC culture, Zhai et al functionalized the human mesenchymal stem cell (hMSC)-derived decellularized extracellular matrix (dECM) with collagen binding peptide-modified exosomes. Thus, the proliferation and differentiation of NSCs were significantly enhanced due to the synergistic effects of the dECM and exosomes [10]. The human foreskin fibroblast-derived dECM can be also enriched with vascular endothelial growth factor A and basic fibroblast growth factor by expressing the collagen-binding domain fused factor genes in host cells during preparation. The growth factor enriched dECM sheet material induced hMSC endothelial differentiation and accelerated angiogenesis, which promoted skin injury repair [11]. The dECM could be also processed into a nanofibrous scaffold for cell growth. A tannin (TA) crosslinked, tympanic membrane-derived dECM and polycaprolactone (PCL) hybrid nanofibers were fabricated by electrospinning and chemical crosslinking. The PCL/dECM/TA nanofibers with proper durability and mechanical properties could be assembled into a spool-shaped membrane for inserting into tympanic membrane perforated sites and exhibited effects on promoting fibroblast adhesion, proliferation, and F-actin distribution [12].

Nature material-based hydrogels are promising three-dimensional scaffolds for various biomedical applications because of their similarity to human tissues in structure and mechanical properties, as well as good biocompatibility. Prof. Jianwu Dai is one of the pioneers in the field of biomaterials and spinal cord regeneration in the world. In this special issue, his group prepared and optimized hybrid gelatin (GL)/hyaluronic acid (HA) scaffolds through visible light-induced photo-crosslinking. The hybrid hydrogels could undergo in situ gelation and fit the defects perfectly, and suppressed scar formation in an HA concentration-dependent manner. The hybrid hydrogels provided a proper inflammatory microenvironment and promoted endogenous NSC migration, neurogenesis, and axon regeneration, which would be a promising scaffold for complete spinal cord injury repair [13]. To endure the conductivity of the hydrogel, a conductive hybrid hydrogel has been fabricated via in situ polymerization of pyrrole into the silk fibroin network. In this conductive hydrogel, the silk hydrogel formed a stable and flexible three-dimensional matrix, while polypyrrole molecules formed the second network and provided conductivity. The silk-PPy hydrogel showed good mechanical properties, conductivity, and sensitivity, and was applied as a biomedical sensor [14]. Furthermore, with 3D bioprinting technology, the double crosslinked alginate hydrogel was constructed to specific morphology and supported hMSC proliferation and chondrogenic differentiation [15]. To promote multiple tissue integration, interface tissue engineering requires the development of biomaterials with anisotropic mechanical properties and a graded distribution of matrix for cell-cell communications and cell-matrix interactions. Thus, recent advances in fabricating biomaterials with gradients stiffness for the regeneration of a functional tissue interface were summarized by Cai et al, and they have introduced the techniques of manufacturing and characterizing scaffolds with stiffness gradient, and highlighted the effects and fundamentals of gradient biomaterials on regulating cellular behavior and interface tissue regeneration [16].

With the continuous development of stem cells and three-dimensional functionalized scaffolds, preclinical and clinical studies of regenerative medicine products have increased. In this special issue, Wang et al investigated the clinical application of collagen membranes with hMSC for nasal septa perforation repair. Eight patients were followed up postoperatively and evaluated the healing process of the perforations, the visual analog scale (VAS), and the nasal mucociliary transit time. With the treatment of the hMSC-laden collagen membrane, most patients presented the improved VAS scores and the shortened transit time. This clinical investigation indicated that the hMSC-loaded collagen membrane is a simple and feasible endoscopic procedure to repair perforated nasal septa and restore satisfactory functional mucosa [17].

Taken together, this Focus Collection includes a series of topical reviews and original research articles that highlight the recent advances in nanomaterials-based drug delivery systems, in vivo bioimaging, and biomaterial scaffold- and stem cell-based regenerative medicines from the investigators of CAS Key Laboratory of Nano-Bio Interface at SINANO, CAS. It is believed that this special issue will present inspiration for researchers in the fields of nano-bio interface for future studies on nanobiomaterials, nanobiotechnologies and precision medicines.

No new data were created or analyzed in this study.