The fabrication of functional assemblies with defined structures through controllable molecular packing under physiological conditions is challenging. Here, modularly designed peptide‐cyanine ...conjugates that intracellularly self‐assembly into 1D columnar superstructures with controlled cyanine aggregation were designed, and they exhibit distinct imaging or photothermal properties. The peptide backbone is cleaved by caspase‐3/7 after entering the cells. Then the self‐assembled residue, with a double cyanine substitution (Pr‐2Cy), forms a P helical column in which H‐aggregated cyanine dyes show 3.4‐fold photothermal conversion efficiency compared to free ones. The self‐assembled residue with a single cyanine substitution (Pr‐1Cy) forms a loose column, in which cyanine dyes with undefined structure have a fluorescence quantum yield of up to 9.5 % (emission at 819 nm in H2O). This work provides a simple way to modify in vivo self‐assembled peptides with functional molecules for achieving desired bio‐applications.
The design of peptide‐cyanine conjugates that intracellularly self‐assemble into a one‐dimensional column with controlled cyanine aggregation exhibit distinct imaging or photothermal properties. Through rational molecular design, the assembly behavior of cyanine dyes is precisely regulated in biological systems, resulting in two kinds of assemblies with different properties. The relationship between structure and function has been studied in detail.
Recently, approaches based on nano‐immunoengineering have been developed to optimize the potency of vaccines while minimizing toxicity. To achieve desirable immune responses, vaccines should be able ...to traffic into lymph nodes (LN) and provide antigen and inflammatory signals for a sufficient temporal duration, to activate the desired cellular and humoral immunity. In that case, the application of nanotechnology in vaccine design provides the possibility of co‐delivering of antigen and adjuvants to the targeted organs, tissues, cells, or even intracellular compartments at the determined time to optimize the qualities of immune responses. Herein, the recent advances on nanovaccine design, including a brief summary of natural and synthetic biomaterials for antigen and adjuvant packing, are reviewed. The emerging approaches for regulating pharmacokinetics of vaccines will be further discussed especially for LN targeting as well as antigen uptake by antigen‐presenting cells. Those advances provide a prospect of shaping immune response by immunoengineering‐based nanovaccines.
Utilizing nano‐immunoengineering approaches to potentiate the potency, quality, and durability of vaccine response is an effective strategy and also a great task. Herein, the current development on the design strategies of nanovaccines, especially from the aspect of improving vaccine pharmacokinetics to provide a theoretical guideline for exploiting novel nanovaccines to bolster immune responses, is summarized.
Modulated molecular design‐based intracellular self‐assembly strategy has showed great potentiality in drug delivery, due to its assembling nature‐resulted optimized drug biodistribution and ...metabolism. The modular designing concept endows the delivery system multiple functions, such as, selectivity and universality to improve the pharmacokinetics of loaded drugs. However, the accurate controlling of the self‐assembling process in desired site to achieve optimal drug delivery is posed great challenges toward rational molecular design. Here, we fabricated a modulated drug‐delivery system (MDS) through intracellular peptide self‐assembly to realize effective drug delivery. MDS was designed based on modulated molecular designing strategy which contains five functional motifs and effectively transformed into fibrous nanostructures inside target cells by caspase3/7 hydrolysis directed in situ self‐assembly. The experimental studies and molecular simulations were carried out to evaluate the successful construction and delivering efficacy of MDS. According to the experimental results and molecular simulation analysis, the percentage of solvent‐exposed surface area of assembling modular (KLVFFAE), as well as its non‐covalent interaction between four other modules synergeticly decide the solubility of molecules. The weak intramolecular forces of the peptide back bone, such as, hydrogen bond, as well as multivalent interactions of the side chains such as, salt bridge and hydrophobic interaction both contribute to the self‐assembly of the molecules. The significant structural difference between delivering molecules optimize the system to adapt hydrophilic and hydrophobic drugs. Finally, the predicted drug delivery molecule specifically recognizes targeted cancer cell lines and self‐assembles to form fibers intracellularly, resulting in prolonged drug retention and accumulation. The regular prediction and rational molecular design will benefit the further construction and optimization of modulated drug delivery platform.
A general modulated drug‐delivery system based on modulated design has realized effective drug delivery. According to the experimental results and theoretical calculations, the general regulations of molecule design are obtained. The regular prediction and rational molecular design will benefit the further construction and optimization of universal drug delivery platform.
In vivo self-assembled nanomedicine Mamuti, Muhetaerjiang; Zheng, Rui; An, Hong-Wei ...
Nano today,
February 2021, 2021-02-00, Letnik:
36
Journal Article
Recenzirano
Display omitted
•The molecular designing, self-assembling behavior and its influence on cascade transportation process were highlighted.•“Self-assembly assisted targeting” contributes to enhance the ...location-selectivity of nanomedicine towards desired site.•The molecular state difference result in deeper penetration at pathological site and quick clearance speed on other organs.•Prospective on molecular design, dynamic self-assembly and relationship between structure and biological effects was emphasized.
The emergence of nanomedicine improved the pharmacokinetics of conventional therapeutic agents through ensuring its optimal biodistribution and targeted accumulation. However, the biological barriers along with the alteration on stability and surface properties of nanomedicine during transportation hinder its clinical translation. In order to address those challenges, we propose a strategy of in vivo self-assembly which combines the dynamic and adaptive behavior of self-assembly with internal biological stimuli to construct self-assembled nanomedicine in vivo. In this review, we focus on the transportation process of in vivo self-assembled nanomedicine, in which we mainly discuss the specific molecular design and its self-assembling process that influence the targeted accumulation towards disease sites. The transportation process of in vivo self-assembled nanomedicine can be described as four cascade processes including the targeting, penetration, accumulation and clearance. Frist, we will provide an update on the construction and working mechanism of in vivo self-assembled nanomedicine. Then, we summarize the molecular designing strategies and discuss its self-assembling process for improving the penetration depth, targeted accumulation and optimal clearance of nanomachines in detail. More importantly, we highlight the influence of the molecular state on its transportation process to emphasize the contribution of molecular state difference of in vivo self-assembled nanomedicine between pathological site and other organs on its targeted accumulation and reduced toxicity. In addition, we summarize its biomedical applications to manifest its potential on clinical translation. Finally, we briefly described our perspective on molecular design, dynamic self-assembling process and the relationship between nanostructure and its biological effects to highlight those challenges in this field.
The rapid development of nanobiotechnology has enabled progress in therapeutic cancer vaccines. These vaccines stimulate the host innate immune response by tumor antigens followed by a cascading ...adaptive response against cancer. However, an improved antitumor immune response is still in high demand because of the unsatisfactory clinical performance of the vaccine in tumor inhibition and regression. To date, a complicated tumor immunosuppressive environment and suboptimal design are the main obstacles for therapeutic cancer vaccines. The optimization of tumor antigens, vaccine delivery pathways, and proper adjuvants for innate immune response initiation, along with reprogramming of the tumor immunosuppressive environment, is essential for therapeutic cancer vaccines in triggering an adequate antitumor immune response. In this review, we aim to review the challenges in and strategies for enhancing the efficacy of therapeutic vaccines. We start with the summary of the available tumor antigens and their properties and then the optimal strategies for vaccine delivery. Subsequently, the vaccine adjuvants focused on the intrinsic adjuvant properties of nanostructures are further discussed. Finally, we summarize the combination strategies with therapeutic cancer vaccines and discuss their positive impact in cancer immunity.
Cancer immunotherapy, leveraging the host's coordinated immune system to fight against tumor has been clinically validated. However, the modest response owing to the multiple ways of tumor immune ...evasion is one of the challenges in cancer immunotherapy. Tumor associated macrophages (TAMs), as a major component of the leukocytes infiltrating in all tumors, play crucial roles in driving cancer initiation, progress and metastasis via multiple mechanisms such as mediating chronic inflammation, promoting angiogenesis, taming protective immune responses, and supporting migration and intravasation. TAMs targeted therapeutics have achieved remarkable successes in clinical trials mostly through the use of small-molecule agents and antibodies. However, efforts for further application have met with challenges of limited efficacy and safety. Nanomaterials can provide versatile approaches to realize the superior spatiotemporal control over immunomodulation to amplify immune responses, ultimately enhancing the therapeutic benefits and reducing toxicity. Here, the potential drugs used in TAM-centered cancer treatment in clinic are summarized and the recent advances of TAMs targeted nanomedicines in this filed are highlighted. More importantly, we focus on how nanomedicine can exert their advantages in spatial and temporal control of immunomodulation.
Display omitted
Due to intrinsic and acquired chemo/radiotherapy-resistance, renal cell carcinoma shows limited therapeutic response to clinically utilized targeting drugs. Here a tumor-activated oncolytic peptide ...nanomachine is devised to selectively lysing tumor cell membrane without causing drug resistance. Specifically, in the acidic tumor microenvironment, the oncolytic peptide nanomachine automatically activated through morphologically transformation from nanoparticles to nanofibrils with restoring α-helical conformation, which physically bind to tumor cell membrane with multiple (spatially correlated and time-resolved) interactions and subsequently lyse local cell membrane. The IC50 of the oncolytic peptide nanomachine is as low as 2.44 μM and it inhibit up to 90% of tumor cells within 2 h with unique bystander killing effect. In vivo, the tumor inhibition rate of the oncolytic peptide nanomachine is 71% without off-target activity and hemolytic activity. These results support that tumor-selective oncolytic peptide nanomachine represent a promising alternative approach for multidrug-resistant tumor treatments by inducing cell membrane lysis.
A tumor-launched oncolytic peptide nanomachine is developed to overcome the multidrug resistance of clear cell renal cell carcinoma. In acid tumor microenvironment, the oncolytic peptide nanomachine launches from “off” to “on” state through conformational switch and morphological transform to expose the α-helical structure on the surface of nanomachine, which lyse membranes selectively and rapidly cause necrosis of tumor cells at a low concentration of nanomachine. Display omitted
•Renal cell carcinoma is a chemotherapy-resistant tumor due to its distinctive gene-defined chemo and radiotherapy resistance.•The oncolytic peptide nanomachine by lysing cell membrane overcome the drug resistance of renal cell carcinoma.•The IC50 of the oncolytic peptide nanomachine is as low as 2.44 μM and it inhibit up to 90% of tumor cells.•The oncolytic peptide nanomachine tumor-selective launched without off-target activity and hemolytic activity.
Cellular immunotherapeutics aim to employ immune cells as anticancer agents. Ex vivo engineering of dendritic cells (DCs), the initial role of an immune response, benefits tumor elimination by ...boosting specific antitumor responses. However, directly activating DCs in vivo is less efficient and therefore quite challenging. Here, we designed a nanoactivator that manufactures DCs through autophagy upregulating in vivo directly, which lead to a high-efficiency antigen presention of DCs and antigen-specific T cells generation. The nanoactivator significantly enhances tumor antigen cross-presentation and subsequent T cell priming. Consequently, in vivo experiments show that the nanoactivators successfully reduce tumor growth and prolong murine survival. Taken together, these results indicate in situ DCs manipulation by autophagy induction is a promising strategy for antigen presentation enhancement and tumor elimination.
Cancer Immunotherapy
In article number 2306248, Yao‐Xin Lin, Hao Wang, and co‐workers report the polymer peptide assembled nanorobot as an elegant tool for CpG delivery. These nanorobots induce ...autophagy‐mediated cell death through structural deformation, resulting in enhanced efficacy of immunotherapy. This innovative approach provides a robust strategy in reinvigorating antitumor immunity.
PDF
