Lipid-Polymer Hybrid "Particle-in-Particle" Nanostructure Gene Delivery Platform Explored for Lyophilizable DNA and mRNA COVID-19 Vaccines.

SARS-CoV-2 has led to a worldwide pandemic, catastrophically impacting public health and the global economy. Herein, a new class of lipid-modified polymer poly (ß-amino esters) (L-PBAEs) is developed via enzyme-catalyzed esterification and further formulation of the L-PBAEs with poly(d,l-lactide-coglycolide)-b-poly(ethylene glycol) (PLGA-PEG) leads to self-assembly into a "particle-in-particle" (PNP) nanostructure for gene delivery. Out of 24 PNP candidates, the top-performing PNP/C12-PBAE nanoparticles efficiently deliver both DNA and mRNA in vitro and in vivo, presenting enhanced transfection efficacy, sustained gene release behavior, and excellent stability for at least 12 months of storage at -20 °C after lyophilization without loss of transfection efficacy. Encapsulated with spike encoded plasmid DNA and mRNA, the lipid-modified polymeric PNP COVID-19 vaccines successfully elicit spike-specific antibodies and Th1-biased T cell immune responses in immunized mice even after 12 months of lyophilized storage at -20 °C. This newly developed lipid-polymer hybrid PNP nanoparticle system demonstrates a new strategy for both plasmid DNA and mRNA delivery with the capability of long-term lyophilized storage.

Erlotinib-Guided Self-Assembled Trifunctional Click Nanotheranostics for Distinguishing Druggable Mutations and Synergistic Therapy of Nonsmall Cell Lung Cancer.

The outcome of molecular targeted therapies is restricted by the ambiguous molecular subtypes of nonsmall cell lung cancer (NSCLC), which are difficult to be defined with druggable mutations, and the inevitable emergence of drug-resistance. Here we used the Cu-catalyzed click chemistry to synthesize a chitosan-based self-assembled nanotheranostics (CE7Ns) composed of a near-infrared (NIR) fluorescent photosensitizer Cy7 and molecular targeted drug erlotinib. The well-characterized CE7Ns can release erlotinib and Cy7 fast under acidic condition in the presence of lysozyme, distinguish three molecular subtypes of NSCLC, and specifically bind to the erlotinib-sensitive epidermal growth factor receptor (EGFR)-mutated PC-9 cells. The uptake of CE7Ns is much more in PC-9 cells than in other NSCLC cells, thus generating a notable fluorescence signal in PC-9 cells. Upon NIR irradiation, Cy7 in CE7Ns produces high reactive oxygen species in PC-9 cells. The synergistic effect between erlotinib-targeted therapy and photodynamic therapy significantly up-regulates cancer suppressor p53 and inhibits Survivin, which results in more apoptosis and cell cycle arrest. Upon intravenous administration, the erlotinib-guided CE7Ns significantly accumulate in PC-9-seeded mouse lungs and produce strong fluorescence. Upon NIR irradiation, CE7Ns significantly inhibit the subcutaneously implanted PC-9 tumor growth. This study provides, for the first time, a novel strategy to synthesize a multifunctional theranostic entity to simultaneously distinguish and image druggable mutations and combine targeted therapy with photodynamic therapy to overcome drug resistance.

ApoE mimetic ameliorates motor deficit and tissue damage in rat spinal cord injury.

Apolipoprotein E (apoE), a plasma protein responsible for transporting lipid and cholesterol, modulates responses of the central nervous system to injury. Small peptides derived from the receptor-binding region of apoE can simulate some important bioactivities of apoE holoprotein and offer neuroprotection against brain injury. We tested whether COG1410, an apoE-mimetic peptide, provides protection in a rat model of spinal cord injury (SCI). Traumatic injury was created at T8 by a cortical impact device. Injured rats were randomized to four treatment groups: vehicle, 0.15, 0.3, or 0.6 mg/kg COG1410; sham surgery rats received vehicle. Basso, Beattie, Bresnahan neurological score was evaluated prior to injury and at 1, 3, 7, and 14 days after injury. Histological changes were evaluated at 14 days. All injured rats lost body weight during the first week following injury. Body weight recovery was significantly improved in rats treated with COG1410. Mechanical impact resulted in severe motor deficit, and most animals had a BBB score of 0-1 at 24 hours postinjury. COG1410-treated rats showed significantly improved functional recovery and ameliorated motor deficit at 14 days postinjury. Histological analysis showed that COG1410 groups had a significantly reduced lesion size at the site of injury, a larger preserved luxol fast blue-stained area, and more visible neurons in the surrounding area of injury. Microglial activation was also significantly suppressed. These findings indicate that this apoE mimetic effectively improved neurological and histological outcome following SCI in rats, and the effect was associated with inhibition of microglial activation.

Optimized inhaled LNP formulation for enhanced treatment of idiopathic pulmonary fibrosis via mRNA-mediated antibody therapy.

Lipid nanoparticle-assisted mRNA inhalation therapy necessitates addressing challenges such as resistance to shear force damage, mucus penetration, cellular internalization, rapid lysosomal escape, and target protein expression. Here, we introduce the innovative "LOOP" platform with a four-step workflow to develop inhaled lipid nanoparticles specifically for pulmonary mRNA delivery. iLNP-HP08LOOP featuring a high helper lipid ratio, acidic dialysis buffer, and excipient-assisted nebulization buffer, demonstrates exceptional stability and enhanced mRNA expression in the lungs. By incorporating mRNA encoding IL-11 single chain fragment variable (scFv), scFv@iLNP-HP08LOOP effectively delivers and secretes IL-11 scFv to the lungs of male mice, significantly inhibiting fibrosis. This formulation surpasses both inhaled and intravenously injected IL-11 scFv in inhibiting fibroblast activation and extracellular matrix deposition. The HP08LOOP system is also compatible with commercially available ALC0315 LNPs. Thus, the "LOOP" method presents a powerful platform for developing inhaled mRNA nanotherapeutics with potential for treating various respiratory diseases, including idiopathic pulmonary fibrosis.

Superiority of native soil core microbiomes in supporting plant growth.

Native core microbiomes represent a unique opportunity to support food provision and plant-based industries. Yet, these microbiomes are often neglected when developing synthetic communities (SynComs) to support plant health and growth. Here, we study the contribution of native core, native non-core and non-native microorganisms to support plant production. We construct four alternative SynComs based on the excellent growth promoting ability of individual stain and paired non-antagonistic action. One of microbiome based SynCom (SC2) shows a high niche breadth and low average variation degree in-vitro interaction. The promoting-growth effect of SC2 can be transferred to non-sterile environment, attributing to the colonization of native core microorganisms and the improvement of rhizosphere promoting-growth function including nitrogen fixation, IAA production, and dissolved phosphorus. Further, microbial fertilizer based on SC2 and composite carrier (rapeseed cake fertilizer + rice husk carbon) increase the net biomass of plant by 129%. Our results highlight the fundamental importance of native core microorganisms to boost plant production.

Apolipoprotein E and peptide mimetics modulate inflammation by binding the SET protein and activating protein phosphatase 2A.

The molecular mechanism by which apolipoprotein E (apoE) suppresses inflammatory cytokine and NO production is unknown. Using an affinity purification approach, we found that peptide mimetics of apoE, derived from its receptor binding domain residues 130-150, bound to the SET protein, which is a potent physiological inhibitor of protein phosphatase 2A (PP2A). Both holo-apoE protein and apoE-mimetic peptides bound to the C-terminal region of SET, which is then associated with an increase in PP2A-mediated phosphatase activity. As physiological substrates for PP2A, the LPS-induced phosphorylation status of signaling MAPK and Akt kinase is reduced following treatment with apoE-mimetic peptides. On the basis of our previous report, in which apoE-mimetic peptides reduced I-κB kinase and NF-κB activation, we also demonstrate a mechanism for reduced production of inducible NO synthase protein and its NO product. These data provide evidence for a novel molecular mechanism by which apoE and apoE-mimetic peptides antagonize SET, thereby enhancing endogenous PP2A phosphatase activity, which reduces levels of phosphorylated kinases, signaling, and inflammatory response.

Microbiome sustains forest ecosystem functions across hierarchical scales.

Forests are highly productive ecosystems that contribute to biogeochemical cycles of carbon and nitrogen, through which it regulates climate and global change. Forests are also spatially highly heterogeneous ecosystems that comprise a multitude of microbial-mediated reactive interfaces. These are mainly the root-soil interface, litter-soil interface, root-root interface, and plant-atmosphere interface. Each of these interfaces has its own unique characteristics, e.g., specific drivers that affect the microbial abundance, nutrient availability, microbial community, and the dominance of certain microbial taxa. Here, we review the microbial-mediated reactive interfaces in forests, focusing on interrelation and dynamics of fungi and bacteria on a broad temporal scale with ecosystem processes ranging from short-term events (e.g., seasonal changes) to long-term stand development suffering a global climate change (e.g., global warming or nitrogen deposition). We argue that in-depth knowledge of forest microbiology can only be obtained by exploring the complex forest microbiome and its ecosystem functions. Underpinning the basis for individual forest variation would ultimately facilitate the formulation of microbiome-based strategies in the future.

Nanoparticle-Mediated RNA Therapy Attenuates Nonalcoholic Steatohepatitis and Related Fibrosis by Targeting Activated Hepatic Stellate Cells.

Chronic liver injury and inflammation triggered by metabolic abnormalities initiate the activation of hepatic stellate cells (HSCs), driving fibrosis and parenchymal dysfunction, culminating in disorders such as nonalcoholic steatohepatitis (NASH). Unfortunately, there are currently no approved drugs capable of effectively treating NASH due to the challenges in addressing fibrosis and restoring extracellular matrix (ECM) homeostasis. We discovered a significant up-regulation of interleukin-11 (IL-11) in fibrotic livers using two well-established murine models of NASH. To leverage this signaling pathway, we developed a nanoparticle (NP)-assisted RNA interfering approach that specifically targets activated HSCs (aHSCs), blocking IL-11/ERK signaling to regulate HSC transdifferentiation along with fibrotic remodeling. The most potent NP, designated NP-AEAA, showed enhanced accumulation in fibrotic livers with NASH and was primarily enriched in aHSCs. We further investigated the therapeutic efficacy of aHSC-targeting NP-AEAA encapsulating small interfering RNA (siRNA) against IL11 or its cognate receptor IL11ra1 (termed siIL11@NP-AEAA or siIL11ra1@NP-AEAA, respectively) for resolving fibrosis and NASH. Our results demonstrate that both siIL11@NP-AEAA and siIL11ra1@NP-AEAA effectively inhibit HSC activation and resolve fibrosis and inflammation in two well-established murine models of NASH. Notably, siIL11ra1@NP-AEAA exhibits a superior therapeutic effect over siIL11@NP-AEAA, in terms of reducing liver steatosis and fibrosis as well as recovering liver function. These results constitute a targeted nanoparticulate siRNA therapeutic approach against the IL-11 signaling pathway of aHSCs in the fibrotic liver, offering a promising therapeutic intervention for NASH and other diseases.

mRNA lipid nanoparticle-mediated pyroptosis sensitizes immunologically cold tumors to checkpoint immunotherapy.

Synergistically improving T-cell responsiveness is promising for favorable therapeutic outcomes in immunologically cold tumors, yet current treatments often fail to induce a cascade of cancer-immunity cycle for effective antitumor immunity. Gasdermin-mediated pyroptosis is a newly discovered mechanism in cancer immunotherapy; however, cleavage in the N terminus is required to activate pyroptosis. Here, we report a single-agent mRNA nanomedicine-based strategy that utilizes mRNA lipid nanoparticles (LNPs) encoding only the N-terminus of gasdermin to trigger pyroptosis, eliciting robust antitumor immunity. In multiple female mouse models, we show that pyroptosis-triggering mRNA/LNPs turn cold tumors into hot ones and create a positive feedback loop to promote antitumor immunity. Additionally, mRNA/LNP-induced pyroptosis sensitizes tumors to anti-PD-1 immunotherapy, facilitating tumor growth inhibition. Antitumor activity extends beyond the treated lesions and suppresses the growth of distant tumors. We implement a strategy for inducing potent antitumor immunity, enhancing immunotherapy responses in immunologically cold tumors.

Injectable Hydrogels for Vascular Tissue Engineering.

Injectable scaffolds made of biodegradable biomaterials can stabilize a myocardial infarct and promote cardiac repair. Here, we describe an injectable, citrate-containing polyester hydrogel which can release citrate as a cell regulator via hydrogel degradation and simultaneously show sustained release of an encapsulated myeloid-derived growth factor (Mydgf). Xu et al. described the synthesis of hydrogel with biocompatible starting chemicals including citric acid and poly(ethylene glycol) diol. The characterization of materials demonstrated that the developed hydrogels possess tunable degradation and mechanical properties and exhibit sustained drug release. The authors also observed improved postmyocardial infarction (MI) heart repair in a rat MI model through coupling the therapeutic effect of the hydrogel degradation product (citrate) with encapsulated Mydgf. In their study, hematoxylin and eosin (H&E) staining and Masson's trichrome staining were performed on heart samples to evaluate the change in heart structure. Furthermore, immunohistochemistry was used to study neovascularization. Their results showed that the intramyocardial injection of Mydgf-loaded citrate-containing hydrogel significantly reduced scar formation and infarct size, increased wall thickness and neovascularization, and improved heart function.

Host Plant Selection Imprints Structure and Assembly of Fungal Community along the Soil-Root Continuum.

The soil fungal community plays pivotal roles in soil nutrient cycling and plant health and productivity in agricultural ecosystems. However, the differential adaptability of soil fungi to different microenvironments (niches) is a bottleneck limiting their application in agriculture. Hence, the understanding of ecological processes that drive fungal microbiome assembly along the soil-root continuum is fundamental to harnessing the plant-associated microbiome for sustainable agriculture. Here, we investigated the factors that shape fungal community structure and assembly in three compartment niches (the bulk soil, rhizosphere, and rhizoplane) associated with tobacco (Nicotiana tabacum L.), with four soil types tested under controlled greenhouse conditions. Our results demonstrate that fungal community assembly along the soil-root continuum is governed by host plant rather than soil type and that soil chemical properties exert a negligible effect on the fungal community assembly in the rhizoplane. Fungal diversity and network complexity decreased in the order bulk soil > rhizosphere > rhizoplane, with a dramatic decrease in Ascomycota species number and abundance along the soil-root continuum. However, facilitations (positive interactions) were enhanced among fungal taxa in the rhizoplane niche. The rhizoplane supported species specialization with enrichment of some rare species, contributing to assimilative community assembly in the rhizoplane in all soil types. Mortierella and Pyrenochaetopsis were identified as important indicator genera of the soil-root microbiome continuum and good predictors of plant agronomic traits. The findings provide empirical evidence for host plant selection and enrichment/depletion processes of fungal microbiome assembly along the soil-root continuum. IMPORTANCE Fungal community assembly along the soil-root continuum is shaped largely by the host plant rather than the soil type. This finding facilitates the implementations of fungi-associated biocontrol and growth-promoting for specific plants in agriculture practice, regardless of the impacts from variations in geographical environments. Furthermore, the depletion of complex ecological associations in the fungal community along the soil-root continuum and the enhancement of facilitations among rhizoplane-associated fungal taxa provide empirical evidence for the potential of community simplification as an approach to target the plant rhizoplane for specific applications. The identified indicators Mortierella and Pyrenochaetopsis along the soil-root microbiome continuum are good predictors of tobacco plant agronomic traits, which should be given attention when manipulating the root-associated microbiome.

Development of antibacterial peptides with efficient antibacterial activity, low toxicity, high membrane disruptive activity and a synergistic antibacterial effect.

The development of new antimicrobial drugs is urgently required to overcome bacterial resistance which is a serious threat to human health. Antimicrobial peptides (AMPs) which are ideal substitutes for traditional antibiotics have a unique mechanism of action and do not easily cause bacterial resistance. Herein, a series of new AMPs were designed and synthesized based on the biological characteristics of natural AMPs (such as the positive charge, α-helical structure and amphiphilicity). Biological screening of the AMPs provided an antimicrobial lipopeptide LP21 with efficient antimicrobial activity, serum stability, low cytotoxicity and high membrane-disruptive activity. Besides, LP21 could self-assemble into spherical aggregates in aqueous solutions which encapsulated TC to form LP21@TC nanomedicine, and the encapsulation efficiency was about 50.03 ± 3.03%. More impressively, both LP21 and LP21@TC nanomedicine displayed significant therapeutic effects in vivo, and the LP21@TC nanomedicine could exert a synergistic antimicrobial effect. This work is expected to provide a new research vision for the design of AMPs and synergistic antibacterial sensitization treatment.

Enzyme-Catalyzed One-Step Synthesis of Ionizable Cationic Lipids for Lipid Nanoparticle-Based mRNA COVID-19 Vaccines.

Ionizable cationic lipid-containing lipid nanoparticles (LNPs) are the most clinically advanced non-viral gene delivery platforms, holding great potential for gene therapeutics. This is exemplified by the two COVID-19 vaccines employing mRNA-LNP technology from Pfizer/BioNTech and Moderna. Herein, we develop a chemical library of ionizable cationic lipids through a one-step chemical-biological enzyme-catalyzed esterification method, and the synthesized ionizable lipids were further prepared to be LNPs for mRNA delivery. Through orthogonal design of experiment methodology screening, the top-performing AA3-DLin LNPs show outstanding mRNA delivery efficacy and long-term storage capability. Furthermore, the AA3-DLin LNP COVID-19 vaccines encapsulating SARS-CoV-2 spike mRNAs successfully induced strong immunogenicity in a BALB/c mouse model demonstrated by the antibody titers, virus challenge, and T cell immune response studies. The developed AA3-DLin LNPs are an excellent mRNA delivery platform, and this study provides an overall perspective of the ionizable cationic lipids, from aspects of lipid design, synthesis, screening, optimization, fabrication, characterization, and application.

The Clinical Efficacy of Platelet-Rich Plasma versus Conventional Drug Injection in the Treatment of Knee Osteoarthritis: A Study Protocol for a Randomized Controlled Trial.

Knee osteoarthritis is a common chronic degenerative joint disease in middle-aged and elderly people. Intra-articular injection for the treatment of knee osteoarthritis is a regularly utilized nonsurgical treatment in modern medicine. Hyaluronic acid (HA) and platelet-rich plasma (PRP) are two frequently employed intra-articular devices. Hyaluronic acid (HA) is an accepted nonsurgical treatment for symptomatic KOA, and platelet-rich plasma is a popular option in the treatment of KOA in recent years. The purpose of this research is to compare the efficacy and safety of intra-articular injection of platelet-rich plasma (PRP) versus hyaluronic acid (HA) on the pain score scale, knee function, and related inflammatory biomarkers in KOA patients using a clinical randomized controlled trial. Participants are being randomized into either the hyaluronic acid (HA) or into the platelet-rich plasma (PRP) group. All patients receive 4 weeks of treatment (once a week), and well-being support and quadriceps training (3 times a week). The primary outcomes are measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the visual analog scale (VAS). The secondary outcomes include the activities of daily living score, erythrocyte sedimentation rate, C-reactive protein testing, interleukin-6 levels, and X-ray examination. In order to monitor the occurrence of irregularities and abnormalities, patients are assessed at each visit, and restorative treatment is given if necessary. The results of this clinical trial will verify the efficacy of PRP and HA in the treatment of KOA and provide important evidence for the clinical treatment of KOA. The trial was enlisted at the Chinese Clinical Trial Registry on 26 September 2020 (ChiCTR2000038635).

Next-Generation Vaccines: Nanoparticle-Mediated DNA and mRNA Delivery.

Nucleic acid vaccines are a method of immunization aiming to elicit immune responses akin to live attenuated vaccines. In this method, DNA or messenger RNA (mRNA) sequences are delivered to the body to generate proteins, which mimic disease antigens to stimulate the immune response. Advantages of nucleic acid vaccines include stimulation of both cell-mediated and humoral immunity, ease of design, rapid adaptability to changing pathogen strains, and customizable multiantigen vaccines. To combat the SARS-CoV-2 pandemic, and many other diseases, nucleic acid vaccines appear to be a promising method. However, aid is needed in delivering the fragile DNA/mRNA payload. Many delivery strategies have been developed to elicit effective immune stimulation, yet no nucleic acid vaccine has been FDA-approved for human use. Nanoparticles (NPs) are one of the top candidates to mediate successful DNA/mRNA vaccine delivery due to their unique properties, including unlimited possibilities for formulations, protective capacity, simultaneous loading, and delivery potential of multiple DNA/mRNA vaccines. This review will summarize the many varieties of novel NP formulations for DNA and mRNA vaccine delivery as well as give the reader a brief synopsis of NP vaccine clinical trials. Finally, the future perspectives and challenges for NP-mediated nucleic acid vaccines will be explored.

An apolipoprotein E-mimetic stimulates axonal regeneration and remyelination after peripheral nerve injury.

Elevated apolipoprotein E (apoE) synthesis within crushed sciatic nerves advocates that apoE could benefit axonal repair and reconstruction of axonal and myelin membranes. We created an apoE-mimetic peptide, COG112 (acetyl-RQIKIWFQNRRMKWKKCLRVRLASHLRKLRKRLL-amide), and found that postinjury treatment with COG112 significantly improved recovery of motor and sensory function following sciatic nerve crush in C57BL/6 mice. Morphometric analysis of injured sciatic nerves revealed that COG112 promoted axonal regrowth after 2 weeks of treatment. More strikingly, the thickness of myelin sheaths was increased by COG112 treatment. Consistent with these histological findings, COG112 potently elevated growth associated protein 43 (GAP-43) and peripheral myelin protein zero (P0), which are markers of axon regeneration and remyelination, respectively. Electron microscopic examination further suggested that the apoE-mimetic COG112 may increase clearance of myelin debris. Schwann cell uptake of cholesterol-containing low-density lipoprotein particles was selectively enhanced by COG112 treatment in a Schwann cell line S16. Moreover, COG112 significantly promoted axon elongation in primary dorsal root ganglion cultures from rat pups. Considering that cholesterol and lipids are needed for reconstructing myelin sheaths and axon extension, these data support a hypothesis where supplementation with exogenous apoE-mimetics such as COG112 may be a promising strategy for restoring lost functional and structural elements following nerve injury.

Nanoparticle depots for controlled and sustained gene delivery.

Gene therapy is one of the most promising medical fields which holds the potential to rapidly advance the treatment of difficult ailments such as cancer as well as inherited genetic diseases. However, clinical translation is limited by several drug delivery hurdles including renal clearance, phagocytosis, enzymatic degradation, protein absorption, as well as cellular internalization barriers. Additionally, successful treatments require sustained release of drug payloads to maintain the effective therapeutic level. As such, controlled and sustained release is a significant concern as the localization and kinetics of nucleic acid therapeutics can significantly influence the therapeutic efficacy. This is an unmet need which calls for the development of controlled-release nanoparticle (NP) technologies to further improve the gene therapy efficacy by prolonging the release of nucleic acid drug payload for sustained, long-term gene expression or silencing. Herein, we present a polymeric NP system with sustained gene delivery properties, which can be synthesized using biodegradable and biocompatible polymers via self-assembly. The NP delivery system is composed of a polymeric NP which acts as a drug depot encapsulating cationic polymer/nucleic acid complexes, facilitating the enhanced retention and prolonged release of the gene payload. The NPs showed excellent cellular biocompatibility and gene delivery efficacy using the green fluorescent protein (GFP) encoded DNA plasmid (pGFP) as a reporter gene. Sustained release of the pGFP payload was shown over a period of 8 days. The physicochemical properties such as morphology, particle size, zeta potential, pGFP encapsulation efficiency and biological properties such as pGFP release profile, in vitro cytotoxicity and transfection efficacy in Hek 293 cells were characterized and evaluated. Importantly, the NP-mediated sustained release of pGFP generates enhanced GFP expression over time. We expect this NP-mediated gene delivery system to provide safe and sustained release of various nucleic acid-based therapeutics with applications in both fundamental biological studies and clinical translations.

Use of lung-specific exosomes for miRNA-126 delivery in non-small cell lung cancer.

Engineered exosomes have become popular drug delivery carriers for cancer treatment. This is partially due to the interesting property, i.e. exosome organotropism, which plays an important role in organ distribution post systemic administration. Here, we demonstrated that breast cancer (MDA-MB-231) cell-derived exosomes (231-Exo) could be specifically internalized by non-small cell lung cancer cells via a specific interaction between overexpressed integrin ß4 (on exosomes) and surfactant protein C (SPC) on the cancer cells. We showed that 231-Exo was capable of recognizing A549 cells in blood and effectively escaping from the immune surveillance system in vitro. Once loaded with microRNA molecules in the exosome carriers, the resulting, miRNA-126 loaded 231-Exo (miRNA-231-Exo) strongly suppressed A549 lung cancer cell proliferation and migration through the interruption of the PTEN/PI3K/AKT signaling pathway. Intravenous administration of the miRNA-126 laden exosomes led to an effective lung homing effect in mice. When tested in a lung metastasis model, miRNA-231-Exo resulted in an efficacious effect in inhibiting the formulation of lung metastasis in vivo. Collectively, our data demonstrated the possibility of using the organotropism feature of exosomes in exosome carrier design, generating a potent anti-metastasis effect in a mouse model.

Publisher Correction: Eliminating blood oncogenic exosomes into the small intestine with aptamer-functionalized nanoparticles.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Challenges and Opportunities from Basic Cancer Biology for Nanomedicine for Targeted Drug Delivery.

BACKGROUND: Effective cancer therapy is still a great challenge for modern medical research due to the complex underlying mechanisms of tumorigenesis and tumor metastasis, and the limitations commonly associated with currently used cancer therapeutic options. Nanotechnology has been implemented in cancer therapeutics with immense potential for improving cancer treatment. OBJECTIVE: Through information about the recent advances regarding cancer hallmarks, we could comprehensively understand the pharmacological effects and explore the mechanisms of the interaction between the nanomaterials, which could provide opportunities to develop mechanism-based nanomedicine to treat human cancers. METHODS: We collected related information and data from articles. RESULTS: In this review, we discussed the characteristics of cancer including tumor angiogenesis, abnormalities in tumor blood vessels, uncontrolled cell proliferation markers, multidrug resistance, tumor metastasis, cancer cell metabolism, and tumor immune system that provide opportunities and challenges for nanomedicine to be directed to specific cancer cells and portray the progress that has been accomplished in application of nanotechnology for cancer treatment. CONCLUSION: The information presented in this review can provide useful references for further studies on developing effective nanomedicine for the treatment of cancer.