Surface functionalization of nanoparticles for nanomedicine

Control of interactions between nanoparticles and biosystems is essential for the effective utilization of these materials in biomedicine. A wide variety of nanoparticle surface structures have been developed for imaging, sensing, and delivery applications. In this research Highlight, we will emphasize advances in tailoring nanoparticle interfaces for implementation in nanomedicine.     

Hydrogen peroxide-generating nanomedicine for enhanced chemodynamic therapy

Chemodynamic therapy(CDT) is an emerging endogenous stimulation activated tumor treatment approach that exploiting iron-containing nanomedicine as catalyst to convert hydrogen peroxide(H_2O_2)into toxic hydroxyl radical(·OH) through Fenton reaction.Due to the unique characteristics(weak acidity and the high H_2O_2 level) of the tumor microenvironment,CDT has advantages of high selectivity and low side effect.However,as an important substrate of Fenton reaction,the endogenous H_2O_2 in tumor is still insufficient,which may be an important factor limiting the efficacy of CDT.In order to optimize CDT,various H_2O_2-generating nanomedicines that can promote the production of H_2O_2 in tumor have been designed and developed for enhanced CDT.In this review,we summarize recently developed nanomedicines based on catalytic enzymes,nanozymes,drugs,metal peroxides and bacteria.Finally,the challenges and possible development directions for further enhancing CDT are prospected.     

Precise nanomedicine for intelligent therapy of cancer

Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.     

Photo-responsive NIR-II biomimetic nanomedicine for efficient cancer-targeted theranostics

In pancreatic cancer, the special barrier system formed by a large number of stromal cells severely hinders drug penetration in deep tumor tissues, resulting in low treatment efficiency. Cell membrane protein-camouflaged liposomal nanomedicines have cancer cell targeting abilities, whereas near-infrared two-zone (NIR-II) fluorescence imaging can achieve deep tissue penetration due to its long light wavelength (1,000–1,700 nm). To combine the cell membrane-based biomimetic technology with NIR-II fluorescence imaging, we constructed a biomimetic nanomedicine (BLIPO-I/D) by camouflaging indocyanine green-doxorubicin (ICG-DOX) liposomes with SW1990 pancreatic cancer cell membrane. The nanomedicine exhibited light-controlled DOX release and high pancreatic cancer treatment efficiency in vitro and in vivo. BLIPO-I/D showed the ability of targeted delivery of a large number of liposomes to pancreatic tumor tissues through homologous targeting of SW1990 cell membranes, which increased the NIR-II fluorescence imaging intensity. Irradiation of the liposomes taken up by pancreatic tumor tissues with near-infrared light (808 nm) triggered the rapid release of DOX from the liposomes, induced the photothermal and photodynamic effects of ICG, which exerted anti-tumor effects. Therefore, the fabricated biomimetic liposomal nanomedicine BLIPO-I/D is expected to achieve precise theranostics of pancreatic cancer.     

Theranostic nanomedicine by surface nanopore engineering

Theranostic nanomedicine that integrates diagnostic and therapeutic agents into one nanosystem has gained considerable momentum in the field of cancer treatment. Among diverse strategies for achieving theranostic capabilities, surface-nanopore engineering based on mesoporous silica coating has attracted great interest because of their negligible cytotoxicity and chemically active surface that can be easily modified to introduce various functional groups(e.g.,-COOH,-NH_2,-SH, etc.) via silanization, which can satisfy various requirements of conjugating biological molecules or functional nanoparticles. In addition,the nanopore-engineered biomaterials possess large surface area and high pore volume, ensuring desirable loading of therapeutic guest molecules. In this review, we comprehensively summarize the synthetic procedure/paradigm of nanopore engineering and further broad theranostic applications. Such nanopore-engineering strategy endows the biocompatible nanocomposites(e.g., Au,Ag, graphene, upconversion nanoparticles, Fe_3O_4, MXene, etc.) with versatile functional moieties, which enables the development of multifunctional nanoplatforms for multimodal diagnostic bio-imaging, photothermal therapy, photodynamic therapy,targeted drug delivery, synergetic therapy and imaging-guided therapies. Therefore, mesoporous silica-based surface-nanopore engineering integrates intriguing unique features for broadening the biomedical applications of the single mono-functional nanosystem, facilitating the development and further clinical translation of theranostic nanomedicine.     

From self-assembly fundamental knowledge to nanomedicine developments

This review highlights the key role of NMR techniques in demonstrating the molecular aspects of the self-assembly of surfactant molecules that nowadays constitute the basic knowledge which modern nanoscience relies on. The aim is to provide a tutorial overview.     

Redox-responsive micelles integrating catalytic nanomedicine and selective chemotherapy for effective tumor treatment

Chemotherapy is one of the most conventional modalities for cancer therapy. However, the high multidrug resistance of tumor cells still limited the clinical application of current chemotherapy. Considering the ability of nitric oxide (NO) to modulate potent P-glycoprotein to inhibit multi-drug resistance, a synergistic methodology combining chemotherapy and sustained NO generation is an ideal way to further promote the chemotherapy. Herein, a multi-functional micelle with tumor-selective chemotherapy driven by redox-triggered doxorubicin (DOX) release and drug resistance inhibition based on intracellular NO generation was fabricated for effective tumor treatment. The micelle consists of DOX as core, arginine/glucose oxidase (Arg/GOx) as shell and redox-responsive disulfide bond as a linker, which is denoted as micelle-DOX-Arg-GOx. The Arg serves as the biological precursor of nitric oxide for inhibition of multi-drug resistance to promote chemotherapy and GOx catalyzes glucose to produce hydrogen peroxide (H₂O₂) for increasing the generation of NO. Moreover, the glucose supply could be simultaneously blocked by the catalytic process, which further enhanced therapeutic efficiency. This micelle requests a tumor-specific microenvironment (a considerable amount of GSH) to perform synergistic therapeutics including chemotherapy, starvation therapy (catalytic medicine), and gas therapy for tumor treatment, which resulted in significant cytotoxicity to tumor tissue.     

Imparting size, shape, and composition control of materials for nanomedicine

This tutorial review presents an overview of strategies for the synthesis and fabrication of organic nanomaterials, specifically those with potential for use in medical applications. Examples include liposomes, micelles, polymer-drug conjugates and dendrimers. Methods of driving shape via"bottom-up" synthetic approaches and thermodynamics and kinetics are discussed. Furthermore, methods of driving shape via"top-down" physical and engineering techniques are also explored. Finally, a novel method (referred to as PRINT) used to produce nanoparticles that are shape-specific, can contain any cargo, and can be easily modified is examined along with its potential future role in nanomedicine.     

Carbon monoxide-releasing micelles for immunotherapy

With the discovery of important biological roles of carbon monoxide (CO), the use of this gas as a therapeutic agent has attracted attention. However, the medical application of this gas has been hampered by the complexity of the administration method. To overcome this problem, several transition-metal carbonyl complexes, such as Ru(CO)(3)Cl(glycinate), [Ru(CO)(3)Cl(2)](2), and Fe(η(4)-2-pyrone)(CO)(3), have been used as CO-releasing molecules both in vitro and in vivo. We sought to develop micellar forms of metal carbonyl complexes that would display slowed diffusion in tissues and thus better ability to target distal tissue drainage sites. Specifically, we aimed to develop a new CO-delivery system using a polymeric micelle having a Ru(CO)(3)Cl(amino acidate) structure as a CO-releasing segment. The CO-releasing micelles were prepared from triblock copolymers composed of a hydrophilic poly(ethylene glycol) block, a poly(ornithine acrylamide) block bearing Ru(CO)(3)Cl(ornithinate) moieties, and a hydrophobic poly(n-butylacrylamide) block. The polymers formed spherical micelles in the range of 30-40 nm in hydrodynamic diameter. Further characterization revealed the high CO-loading capacity of the micelles. CO-release studies showed that the micelles were stable in physiological buffer and serum and released CO in response to thiol-containing compounds such as cysteine. The CO release of the micelles was slower than that of Ru(CO)(3)Cl(glycinate). In addition, the CO-releasing micelles efficiently attenuated the lipopolysaccharide-induced NF-κB activation of human monocytes, while Ru(CO)(3)Cl(glycinate) did not show any beneficial effects. Moreover, cell viability assays revealed that the micelles significantly reduced the cytotoxicity of the Ru(CO)(3)Cl(amino acidate) moiety. This novel CO-delivery system based on CO-releasing micelles may be useful for therapeutic applications of CO.     

CAR-T cells for cancer immunotherapy

Adoptive immunotherapy expressing synthetic chimeric antigen receptors(CAR) on T cells through in vitro modifications represents a new and innovative strategy in cancer treatment. This new approach enables T cells to recognize and bind tumor antigens via a single-chain variable fragment recognition domain, circumventing the restriction of major histocompatibility complex. This review summarized the structure/design of CAR-T cells and the evolution process this technology went through, displaying...     

Applications of magnetic materials separation in biological nanomedicine

As a result of their advantages for superparamagnetic properties, good biocompatibility, and high binding capacity, functionalized magnetic materials became widely popular over the past couple of decades, being applied on large scale in various processes of sample preparation for biomedicine. In this work, we perform an in‐depth review on the current progress in the field of magnetic bead separation, discussing in detail the physical basis of this process, various synthesis methods and surface modification strategies. We place special focus of attention as well on the latest applications of magnetic polymer microspheres in cell separation, protein purification, immobilized enzyme, nucleic acid separation, and extraction of bioactive compounds with low molecular weight. Existing problems are highlighted and possible trends of magnetic separation techniques for biomedicine in the future are proposed.     

Cell membrane-coated nanoparticles for immunotherapy

Nanoparticle-based disease detection, prevention and therapies have gained increased interests in biomedical applications, owing to their significant advantages in therapeutic efficacy and safety. Nonetheless, suffering from the challenges including fast recognition and clearance of foreign nanoparticles by innate immune system before arriving at diseased regions, clinical applications of nanoparticles are usually intercepted. Among various strategies for reducing non-specific phagocytosis and e...     

Chemistry of two-dimensional MXene nanosheets in theranostic nanomedicine

Transition metal carbide,carbonitride and nitride MXenes,as the emerging two-dimensional(2D)nanomaterials,have aroused burgeoning research interest in a broad range of applications ranging from energy conversion to biomedicines attributing to their distinctive planar nanostructure,physiochemical properties and biological effects.They are featured with fascinating electronic,optical,magnetic,mechanical and thermal properties,which exert significant roles in biomedical applications of 2D MXenes.In this review,we briefly summarize the recent research progress of 2D MXenes and highlight their intrinsic chemistry in theranostic nanomedicines,focusing on the synthetic chemistry for MXenes construction,surface chemistry for surface engineering,physiochemical property for theranostic application and biological chemistry for biosafety evaluation.Furthermore,based on the current achieve ments on MXenes,their potential research directio n,critical challenges and future development in biomedicine are also discussed.It is highly expected that 2D MXene-based nanosystems would have a broad application prospect in theranostic biomedicine provided the current facing critical issues and challenges are adequately solved.     

Emerging nanomedicine and prodrug delivery strategies for the treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic and recurrent disease of the gastrointestinal tract, mainly including Crohn's disease (CD) and ulcerative colitis (UC). However, current approaches against IBD do not precisely deliver drugs to the inflammatory site, which leads to life-long medication and serious side effects that can adversely impact patients’ adherence. It is necessary to construct optimal drug delivery systems (DDSs) that can target drugs to the region of inflammation, thereby improve therapeutic efficacy and reduce side effects. With the burgeoning development of nanotechnology-based nanomedicines (NMs) and prodrug strategy, remarkable progresses in the treatment of IBD have been made in recent years. Herein, the latest advances are outlined at the intersection of IBD treatment and nanotherapeutics as well as prodrug therapy. First, the pathophysiological microenvironment of inflammatory sites of IBD is introduced in order to rationally design potential NMs and prodrugs. Second, the necessity of NMs for the IBD therapy is elaborated, and the representative nanotherapeutics via passive targeted and active targeted NMs developed to treat the IBD are overviewed. Furthermore, the emerging prodrug-based therapeutics are summarized, including 5-aminosalicylic acid-, amino acid-, and carbohydrate-conjugated prodrugs. Finally, the design considerations and perspectives of these NMs and prodrugs-driven IBD therapeutics in the clinical translation are spotlighted.     

A potential nanomedicine consisting of heparin-loaded polysaccharide nanocarriers for the treatment of asthma

A new nanomedicine consisting of chitosan/carboxymethyl-β-cyclodextrin loaded with unfractioned or low-molecular-weight heparin is described and its potential in asthma treatment is evaluated. The nanoparticles are prepared by ionotropic gelation showing a size that between 221 and 729 nm with a positive zeta potential. The drug association efficiency is higher than 70%. Developed nanosystems are stable in Hank's balanced salt solution at pH = 6.4, releasing the drug slowly. Ex vivo assays show that nanocarriers lead to an improvement of heparin preventing mast cell degranulation. These results agree with the effective cellular internalization of the fluorescently labeled nanocarriers, and suggest these nanomedicines as promising formulations for asthma treatment.     

Application of oxygen vacancy defects in enhanced anti-cancer nanomedicine

Nanomedicine has become an important development direction of modern medicine, and provides a new way for cancer theranostics. To extend the superior physicochemical property of nanomedicine and enhance their role in cancer theranostics,various strategies have been proposed. Among them, the introduction of oxygen vacancies can enhance the separation of electron-hole pairs and improve the nanomaterials’ catalytic activity, which is beneficial for cancer diagnosis and treatment. This review briefl...     

Multifunctional dendritic polymers in nanomedicine: opportunities and challenges

Nanotechnology has resulted in materials that have greatly improved the effectiveness of drug delivery because of their ability to control matter on the nanoscale. Advanced forms of nanomedicine have been synthesized for better pharmacokinetics to obtain higher efficacy, less systemic toxicity, and better targeting. These criteria have long been the goal in nanomedicine, in particular, for systemic applications in oncological disorders. Now, the "holy grail" in nanomedicine is to design and synthesize new advanced macromolecular nanocarriers and to translate them from lab to clinic. This review describes the current and future perspectives of nanomedicine with particular emphasis on the clinical targets in cancer and inflammation. The advanced forms of liposomes and polyethylene glycol (PEG) based nanocarriers, as well as dendritic polymer conjugates will be discussed with particular attention paid to designs, synthetic strategies, and chemical pathways. In this critical review, we also report on the current status and perspective of dendritic polymer nanoconjugate platforms (e.g. polyamidoamine dendrimers and dendritic polyglycerols) for cellular localization and targeting of specific tissues (192 references).     

The blooming intersection of transcatheter hepatic artery chemoembolization and nanomedicine

Transcatheter hepatic artery chemoembolization(TACE) is a universal treatment for patients with hepatocellular carcinoma(HCC) that inhibits tumor growth by cutting off the blood supply and provides chemotherapeutics locally to the tumor.The strategy of combining TACE formulation with image-guided ablation holds tremendous potential,but patient tolerance and undesired toxicity/immunosuppression remains a challenge.The application of nanotechnology in TACE opens new doors for the treatment of HCC....     

Cisplatin-loaded polymer/magnetite composite nanoparticles as multifunctional therapeutic nanomedicine

Multifunctional nanocarriers with multilayer core-shell architecture were prepared by coating superparamagnetic Fe3O4 nanoparticles with diblock copolymer folate-poly（ethylene glycol）-b-poly（glycerol monomethacrylate） （FA-PEG-b- PGMA）, and triblock copolymer methoxy poly（ethylene glycol）-b-poly（2-（dimethylamino） ethyl methacrylate）-b- poly（glycerol monomethacrylate） （MPEG-b-PDMA-b-PGMA）. The PGMA segment was attached to the surfaces of Fe304 nanoparticles, and the outer PEG shell imparted biocompatibility. In addition, folate was conjugated onto the surfaces of the nanocarriers. Cisplatin was then loaded into the nanocarrier by coordination between the Pt atom in cisplatin and the amine groups in the inner shell of the multilayer architecture. The loaded cisplatin showed pH-responsive release： slower release at pH 7.4 （i.e. mimicking the blood environment） and faster release at more acidic pH （i.e. mimicking endosome/lysosome conditions）. All of the cisplatin-loaded nanoparticles showed concentration-dependent cytotoxicity in HeLa cells. However, the folate-conjugated cisplatin-loaded carriers exhibited higher cytotoxicity in HeLa cells than non-folate conjugated cisplatin-loaded carriers.