Observation of plaid-like spin splitting in a noncoplanar antiferromagnet.

Spatial, momentum and energy separation of electronic spins in condensed-matter systems guides the development of new devices in which spin-polarized current is generated and manipulated1-3. Recent attention on a set of previously overlooked symmetry operations in magnetic materials4 leads to the emergence of a new type of spin splitting, enabling giant and momentum-dependent spin polarization of energy bands on selected antiferromagnets5-10. Despite the ever-growing theoretical predictions, the direct spectroscopic proof of such spin splitting is still lacking. Here we provide solid spectroscopic and computational evidence for the existence of such materials. In the noncoplanar antiferromagnet manganese ditelluride (MnTe2), the in-plane components of spin are found to be antisymmetric about the high-symmetry planes of the Brillouin zone, comprising a plaid-like spin texture in the antiferromagnetic (AFM) ground state. Such an unconventional spin pattern, further found to diminish at the high-temperature paramagnetic state, originates from the intrinsic AFM order instead of spin-orbit coupling (SOC). Our finding demonstrates a new type of quadratic spin texture induced by time-reversal breaking, placing AFM spintronics on a firm basis and paving the way for studying exotic quantum phenomena in related materials.

Surface-anchored microbial enzyme-responsive solid lipid nanoparticles enabling colonic budesonide release for ulcerative colitis treatment.

Colon-targeted oral drug delivery systems (CDDSs) are desirable for the treatment of ulcerative colitis (UC), which is a disease with high relapse and remission rates associated with immune system inflammation and dysregulation localized within the lining of the large bowel. However, the success of current available approaches used for colon-targeted therapy is limited. Budesonide (BUD) is a corticosteroid drug, and its rectal and oral formulations are used to treat UC, but the inconvenience of rectal administration and the systemic toxicity of oral administration restrict its long-term use. In this study, we designed and prepared colon-targeted solid lipid nanoparticles (SLNs) encapsulating BUD to treat UC by oral administration. A negatively charged surfactant (NaCS-C12) was synthesized to anchor cellulase-responsive layers consisting of polyelectrolyte complexes (PECs) formed by negatively charged NaCS and cationic chitosan onto the SLNs. The release rate and colon-specific release behavior of BUD could be easily modified by regulating the number of coated layers. We found that the two-layer BUD-loaded SLNs (SLN-BUD-2L) with a nanoscale particle size and negative zeta potential showed the designed colon-specific drug release profile in response to localized high cellulase activity. In addition, SLN-BUD-2L exhibited excellent anti-inflammatory activity in a dextran sulfate sodium (DSS)-induced colitis mouse model, suggesting its potential anti-UC applications.

Advances in modification and delivery of nucleic acid drugs. / æ ¸é ¸ç±»è¯ç‰©çš„ä¿®é¥°å’Œé€’é€ç ”ç©¶è¿›å±•.

Nucleic acid-based drugs, such as RNA and DNA drugs, exert their effects at the genetic level. Currently, widely utilized nucleic acid-based drugs include nucleic acid aptamers, antisense oligonucleotides, mRNA, miRNA, siRNA and saRNA. However, these drugs frequently encounter challenges during clinical application, such as poor stability, weak targeting specificity, and difficulties in traversing physiological barriers. By employing chemical modifications of nucleic acid structures, it is possible to enhance the stability and targeting specificity of certain nucleic acid drugs within the body, thereby improving delivery efficiency and reducing immunogenicity. Moreover, utilizing nucleic acid drug carriers can facilitate the transportation of drugs to lesion sites, thereby aiding efficient intracellular escape and promoting drug efficacy within the body. Currently, commonly employed delivery carriers include virus vectors, lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, protein carriers and extracellular vesicles. Nevertheless, individual modifications or delivery carriers alone are insufficient to overcome numerous obstacles. The integration of nucleic acid chemical modifications with drug delivery systems holds promise for achieving enhanced therapeutic effects. However, this approach also presents increased technical complexity and clinical translation costs. Therefore, the development of nucleic acid drug carriers and nucleic acid chemical modifications that are both practical and simple, while maintaining high efficacy, low toxicity, and precise nucleic acid delivery, has become a prominent research focus in the field of nucleic acid drug development. This review comprehensively summarizes the advancements in nucleic acid-based drug modifica-tions and delivery systems. Additionally, strategies to enhance nucleic acid drug delivery efficiency are discussed, with the aim of providing valuable insights for the translational application of nucleic acid drugs.

Wavelength extension and power improvement of red Pr3+:YLF lasers.

High-power red lasers (mainly at 639 and 670 nm) based on Pr3+:YLF crystals have been presented in many works. However, the spectral resources of Pr3+:YLF in the red region have not been fully developed to obtain lasers due to their relatively low emission cross sections and the irrepressible strong emission at ∼639 nm. In this work, we propose a scheme to further develop the spectral resources of Pr3+:YLF in the red region and improve the red laser powers based on this crystal. The laser wavelengths are obtained from 634.5 to 674.7 nm (continuous tunings are achieved at some wavebands). To the best of our knowledge, the output powers obtained at 638.7, 644.6, 670.1, and 674.7 nm (2.88 W, 1.87 W, 3.55 W, and 1.73 W, respectively) are the highest to date. Furthermore, lasing originating from the 3P2 energy level of Pr3+:YLF (∼653 nm) is realized for the first time.

Glutathione-Responsive Magnetic Nanoparticles for Highly Sensitive Diagnosis of Liver Metastases.

Liver metastasis (LM) occurs in various cancers, and its early and accurate diagnosis is of great importance. However, the detection of small LMs is still a great challenge because of the subtle differences between normal liver tissue and small metastases. Herein, we prepare glutathione (GSH)-responsive hyaluronic acid-coated iron oxide nanoparticles (HIONPs) for highly sensitive diagnosis of LMs through a facile one-pot method. HIONPs greatly enhance the signal of MRI in tumor metastases as T1 contrast agent (CA), whereas they substantially decrease the signal of liver as T2 CA as they aggregate into clusters upon the high GSH in liver. Consequently, MRI contrasted by HIONPs clearly distinguishes metastatic tumors (bright) from surrounding liver tissues (dark). HIONPs with superior LM contrasting capability and facile synthesis are very promising for clinical translation and indicate a new strategy to develop an ultrasensitive MRI CA for LM diagnosis that exploits high GSH level in the liver.

Macrophage-Mediated Tumor Cell Phagocytosis: Opportunity for Nanomedicine Intervention.

Macrophages are one of the most abundant non-malignant cells in the tumor microenvironment, playing critical roles in mediating tumor immunity. As important innate immune cells, macrophages possess the potential to engulf tumor cells and present tumor-specific antigens for adaptive antitumor immunity induction, leading to growing interest in targeting macrophage phagocytosis for cancer immunotherapy. Nevertheless, live tumor cells have evolved to evade phagocytosis by macrophages via the extensive expression of anti-phagocytic molecules, such as CD47. In addition, macrophages also rapidly recognize and engulf apoptotic cells (efferocytosis) in the tumor microenvironment, which inhibits inflammatory responses and facilitates immune escape of tumor cells. Thus, intervention of macrophage phagocytosis by blocking anti-phagocytic signals on live tumor cells or inhibiting tumor efferocytosis presents a promising strategy for the development of cancer immunotherapies. Here, the regulation of macrophage-mediated tumor cell phagocytosis is first summarized, followed by an overview of strategies targeting macrophage phagocytosis for the development of antitumor therapies. Given the potential off-target effects associated with the administration of traditional therapeutics (for example, monoclonal antibodies, small molecule inhibitors), we highlight the opportunity for nanomedicine in macrophage phagocytosis intervention.

Prodrug polymeric micelles integrating cancer-associated fibroblasts deactivation and synergistic chemotherapy for gastric cancer.

BACKGROUND: The prognosis of patients with advanced gastric cancer (GC) remains unsatisfactory owing to distant metastasis and resistance to concurrent systemic therapy. Cancer-associated fibroblasts (CAFs), as essential participators in the tumor microenvironment (TME), play a vital role in tumor progression. Thus, CAFs-targeting therapy is appealing for remodeling TME and sensitizing GC to conventional systemic therapy. METHODS: Amphiphilic SN38 prodrug polymeric micelles (PSN38) and encapsulated the hydrophobic esterase-responsive prodrug of Triptolide (TPL), triptolide-naphthalene sulfonamide (TPL-nsa), were synthesized to form PSN38@TPL-nsa nanoparticles. Then, CAFs were isolated from fresh GC tissues and immortalized. TPL at low dose concentration was used to investigate its effect on CAFs and CAFs-induced GC cells proliferation and migration. The synergistic mechanism and antitumor efficiency of SN38 and TPL co-delivery nanoparticle were investigated both in vitro and in vivo. RESULTS: Fibroblast activation protein (FAP), a marker of CAFs, was highly expressed in GC tissues and indicated poorer prognosis. TPL significantly reduced CAFs activity and inhibited CAFs-induced proliferation, migration and chemotherapy resistance of GC cells. In addition, TPL sensitized GC cells to SN38 treatment through attenuated NF-κB activation in both CAFs and GC cells. PSN38@TPL-nsa treatment reduced the expression of collagen, FAP, and α-smooth muscle actin (α-SMA) in tumors. Potent inhibition of primary tumor growth and vigorous anti-metastasis effect were observed after systemic administration of PSN38@TPL-nsa to CAFs-rich peritoneal disseminated tumor and patient-derived xenograft (PDX) model of GC. CONCLUSION: TPL suppressed CAFs activity and CAFs-induced cell proliferation, migration and chemotherapy resistance to SN38 of GC. CAFs-targeted TPL and SN38 co-delivery nanoparticles exhibited potent efficacy of antitumor and reshaping TME, which was a promising strategy to treat advanced GC.

A Novel Solid Artificial Diet for Zeugodacus cucurbitae (Diptera: Tephritidae) Larvae With Fitness Parameters Assessed by Two-Sex Life Table.

The melon fly, Zeugodacus cucurbitae (Coquillett), is a serious pest of many fruits and vegetables throughout the world. Here we have developed an easy and quick-to-prepare solid medium with multiple benefits including reductions in post-rearing waste, storage space, and labor for rearing Z. cucurbitae larvae. The development time from egg to pupa was 19.11 d when larvae were reared on the artificial diet, slightly longer than 17.73 d on pumpkin and 17.13 d on cucumber. Zeugodacus cucurbitae achieved higher values of pupal weight, length, and width on the artificial diet than two natural diet controls. The rates of pupation and adult emergence of Z. cucurbitae grown on the solid medium were comparable with those on pumpkin and cucumber. Furthermore, determined by age-specific two-sex life table method, the age-specific survival rate of Z. cucurbitae was higher on the artificial diet than cucumber but lower than pumpkin. The reproductive ability and population dynamics of Z. cucurbitae were not significantly affected on the solid medium compared with those on the two natural diets. The results suggest that our solid artificial diet is excellent for rearing Z. cucurbitae larvae in laboratory and may be used for its mass rearing, therefore facilitating its research and control.

Drug-binding albumins forming stabilized nanoparticles for efficient anticancer therapy.

Albumin is a serum transport protein, which has been utilized as a carrier for a variety of drugs to improve their delivery efficiency and to obtain favorable pharmacokinetic profiles. However, natural albumin possesses only a few high-affinity binding sites for a limited number of drugs. This results in deficiencies in drug-loading and serum stability, and consequently, in impaired therapeutic efficacy. Herein, BSA was modified with different isothiocyanate conjugates (BSA-ITCs), which self-assembled with paclitaxel (PTX) to produce BSA-ITCs/PTX nanoparticles. Among these BSA-ITCs, phenethyl isothiocyanate (PEITC)-modified BSA (BSA-PEITC35) conjugates effectively loaded PTX and formed highly stable BSA-PEITC35/PTX nanoparticles. Molecular modeling studies suggested that PEITC groups in BSA-PEITC35 can significantly lower the PTX binding free energy. BSA-PEITC35/PTX showed enhanced stability, prolonged blood circulation and increased tumor accumulation than unmodified BSA/PTX, and exerted more potent antitumor activity than both BSA/PTX and Abraxane in subcutaneous mouse tumor models after intravenous administration.

Small molecule induced reactivation of mutant p53 in cancer cells.

The p53 cancer mutant Y220C is an excellent paradigm for rescuing the function of conformationally unstable p53 mutants because it has a unique surface crevice that can be targeted by small-molecule stabilizers. Here, we have identified a compound, PK7088, which is active in vitro: PK7088 bound to the mutant with a dissociation constant of 140 µM and raised its melting temperature, and we have determined the binding mode of a close structural analogue by X-ray crystallography. We showed that PK7088 is biologically active in cancer cells carrying the Y220C mutant by a battery of tests. PK7088 increased the amount of folded mutant protein with wild-type conformation, as monitored by immunofluorescence, and restored its transcriptional functions. It induced p53-Y220C-dependent growth inhibition, cell-cycle arrest and apoptosis. Most notably, PK7088 increased the expression levels of p21 and the proapoptotic NOXA protein. PK7088 worked synergistically with Nutlin-3 on up-regulating p21 expression, whereas Nutlin-3 on its own had no effect, consistent with its mechanism of action. PK7088 also restored non-transcriptional apoptotic functions of p53 by triggering nuclear export of BAX to the mitochondria. We suggest a set of criteria for assigning activation of p53.

Bilateral Context Modeling for Residual Coding in Lossless 3D Medical Image Compression.

Residual coding has gained prevalence in lossless compression, where a lossy layer is initially employed and the reconstruction errors (i.e., residues) are then losslessly compressed. The underlying principle of the residual coding revolves around the exploration of priors based on context modeling. Herein, we propose a residual coding framework for 3D medical images, involving the off-the-shelf video codec as the lossy layer and a Bilateral Context Modeling based Network (BCM-Net) as the residual layer. The BCM-Net is proposed to achieve efficient lossless compression of residues through exploring intra-slice and inter-slice bilateral contexts. In particular, a symmetry-based intra-slice context extraction (SICE) module is proposed to mine bilateral intra-slice correlations rooted in the inherent anatomical symmetry of 3D medical images. Moreover, a bi-directional inter-slice context extraction (BICE) module is designed to explore bilateral inter-slice correlations from bi-directional references, thereby yielding representative inter-slice context. Experiments on popular 3D medical image datasets demonstrate that the proposed method can outperform existing state-of-the-art methods owing to efficient redundancy reduction. Our code will be available on GitHub for future research.

Deep dewatering of sludge and resource recovery of hydroxyapatite: A recyclable approach via ionic liquid biphasic system and hydrogen bonds reformation.

Deep dewatering of Waste Activated Sludge (WAS) through mechanical processes remains inefficient, primarily due to the formation of a stable hydrogen bonding network between the biopolymers and water, which consequently leads to significant water trapped by Extracellular Polymeric Substances (EPS). In this study, a novel and recyclable treatment for WAS based on Ionic Liquids (ILs) was established, named IL-biphasic aqueous system (IL-ABS) treatment. Specifically, the IL-ABS formed in WAS facilitated rapid and efficient in-situ deep dewatering while concurrently recovering hydroxyapatite. The water content decreased from an initial 98.27 % to 65.35 % with IL-ABS, formed by 1-Butyl-3-methylimidazolium bromide (BmimBr) and K3PO4 synthesized from waste H3PO4. Moreover, the recycled BmimBr maintaining the water content of the dewatered sludge consistently between 65.61 % and 67.25 % across five cycles, exhibited remarkable reproducibility. Through three-dimensional excitation-emission matrix, lactate dehydrogenase analyses and confocal laser scanning microscopy, the high concentration of BmimBr in the upper phase effectively disrupted the cells and EPS, which exposed protein and polysaccharide on the EPS surface. Subsequently, the K3PO4 in the lower phase led to an enhanced salting-out effect in WAS. Furthermore, FT-IR analysis revealed that K3PO4 disrupted the original hydrogen bonds between EPS and water. Then, BmimBr formed numerous hydrogen bonds with the sludge flocs, leading to deep dewatering and agglomeration of the sludge flocs during the unique phase separation process of IL-ABS. Notably, sludge-derived hydroxyapatite product exhibited remarkable adsorption capacity for prevalent heavy metal contaminants such as Pb2+, Cd2+ and Cu2+, with efficiencies comparable to those of commercial hydroxyapatite, thereby achieving the resource utilization of waste H3PO4. Moreover, economic calculations demonstrated the suitability of this novel treatment. This innovative treatment exhibits potential for practical applications in the non-mechanical deep dewatering of WAS.

RNA-based modulation of macrophage-mediated efferocytosis potentiates antitumor immunity in colorectal cancer.

Tumor-associated macrophages play pivotal roles in tumor progression and metastasis. Macrophage-mediated clearance of apoptotic cells (efferocytosis) supports inflammation resolution, contributing to immune evasion in colorectal cancers. To reverse this immunosuppressive process, we propose a readily translatable RNA therapy to selectively inhibit macrophage-mediated efferocytosis in tumor microenvironment. A clinically approved lipid nanoparticle platform (LNP) is employed to encapsulate siRNA for the phagocytic receptor MerTK (siMerTK), enabling selective MerTK inhibition in the diseased organ. Decreased MerTK expression in tumor-associated macrophages results in apoptotic cell accumulation and immune activation in tumor microenvironment, leading to suppressed tumor growth and better survival in both liver and peritoneal metastasis models of colorectal cancers. siMerTK delivery combined with PD-1 blockade further produces enhanced antimetastatic efficacy with reactivated intratumoral immune milieu. Collectively, LNP-based siMerTK delivery combined with immune checkpoint therapy may present a feasible modality for metastatic colorectal cancer therapy.

Sulfoxide-containing polymers conjugated prodrug micelles with enhanced anticancer activity and reduced intestinal toxicity.

Poly(ethylene glycol) (PEG) is widely utilized as a hydrophilic coating to extend the circulation time and improve the tumor accumulation of polymeric micelles. Nonetheless, PEGylated micelles often activate complement proteins, leading to accelerated blood clearance and negatively impacting drug efficacy and safety. Here, we have crafted amphiphilic block copolymers that merge hydrophilic sulfoxide-containing polymers (psulfoxides) with the hydrophobic drug 7-ethyl-10-hydroxylcamptothecin (SN38) into drug-conjugate micelles. Our findings show that the specific variant, PMSEA-PSN38 micelles, remarkably reduce protein fouling, prolong blood circulation, and improve intratumoral accumulation, culminating in significantly increased anti-cancer efficacy compared with PEG-PSN38 counterpart. Additionally, PMSEA-PSN38 micelles effectively inhibit complement activation, mitigate leukocyte uptake, and attenuate hyperactivation of inflammatory cells, diminishing their ability to stimulate tumor metastasis and cause inflammation. As a result, PMSEA-PSN38 micelles show exceptional promise in the realm of anti-metastasis and significantly abate SN38-induced intestinal toxicity. This study underscores the promising role of psulfoxides as viable PEG substitutes in the design of polymeric micelles for efficacious anti-cancer drug delivery.

Neutrophil Extracellular Traps-Inhibiting and Fouling-Resistant Polysulfoxides Potently Prevent Postoperative Adhesion, Tumor Recurrence, and Metastasis.

Peritoneal metastasis (PM) is considered one of the most dreaded forms of cancer metastases for both patients and physicians. Aggressive cytoreductive surgery (CRS) is the primary treatment for peritoneal metastasis. Unfortunately, this intensive treatment frequently causes clinical complications, such as postoperative recurrence, metastasis, and adhesion formation. Emerging evidence suggests that neutrophil extracellular traps (NETs) released by inflammatory neutrophils contribute to these complications. Effective NET-targeting strategies thus show considerable potential in counteracting these complications but remain challenging. Here, one type of sulfoxide-containing homopolymer, PMeSEA, with potent fouling-resistant and NET-inhibiting capabilities, is synthesized and screened. Hydrating sulfoxide groups endow PMeSEA with superior nonfouling ability, significantly inhibiting protein/cell adhesion. Besides, the polysulfoxides can be selectively oxidized by ClO- which is required to stabilize the NETs rather than H2O2, and ClO- scavenging effectively inhibits NETs formation without disturbing redox homeostasis in tumor cells and quiescent neutrophils. As a result, PMeSEA potently prevents postoperative adhesions, significantly suppresses peritoneal metastasis, and shows synergetic antitumor activity with chemotherapeutic 5-Fluorouracil. Moreover, coupling CRS with PMeSEA potently inhibits CRS-induced tumor metastatic relapse and postoperative adhesions. Notably, PMeSEA exhibits low in vivo acute and subacute toxicities, implying significant potential for clinical postoperative adjuvant treatment.

Macrophage-evading and tumor-specific apoptosis inducing nanoparticles for targeted cancer therapy.

Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications. However, administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system (MPS). In this study, we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues. The fabricated nanoparticles (TM-CQ/NPs) were coated with fibroblast cell membrane expressing tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages, but increased the nanoparticle uptake in tumor cells. Importantly, this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death receptors. Meanwhile, the encapsulated chloroquine (CQ) further suppressed the uptake of nanoparticles by macrophages, and synergized with TRAIL to induce tumor cell apoptosis. The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer therapy. Together, our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.

Nano-calcipotriol as a potent anti-hepatic fibrosis agent.

Calcipotriol (CAL) has been widely studied as a fibrosis inhibitor and used to treat plaque psoriasis via transdermal administration. The clinical application of CAL to treat liver fibrosis is bottlenecked by its unsatisfactory pharmacokinetics, biodistribution, and side effects, such as hypercalcemia in patients. The exploration of CAL as a safe and effective antifibrotic agent remains a major challenge. Therefore, we rationally designed and synthesized a self-assembled drug nanoparticle encapsulating CAL in its internal hydrophobic core for systematic injection (termed NPs/CAL) and further investigated the beneficial effect of the nanomaterial on liver fibrosis. C57BL/6 mice were used as the animal model, and human hepatic stellate cell line LX-2 was used as the cellular model of hepatic fibrogenesis. Immunofluorescence staining, flow cytometry, western blotting, immunohistochemical staining, and in vitro imaging were used for evaluating the efficacy of NPs/CAL treatment. We found NPs/CAL can be quickly internalized in vitro, thus potently deactivating LX-2 cells. In addition, NPs/CAL improved blood circulation and the accumulation of CAL in liver tissue. Importantly, NPs/CAL strongly contributed to the remission of liver fibrosis without inducing hypercalcemia. Overall, our work identifies a promising paradigm for the development of nanomaterial-based agents for liver fibrosis therapy.

Targeting RAS mutants in malignancies: successes, failures, and reasons for hope.

RAS genes are the most frequently mutated oncogenes and play critical roles in the development and progression of malignancies. The mutation, isoform (KRAS, HRAS, and NRAS), position, and type of substitution vary depending on the tissue types. Despite decades of developing RAS-targeted therapies, only small subsets of these inhibitors are clinically effective, such as the allele-specific inhibitors against KRASG12C . Targeting the remaining RAS mutants would require further experimental elucidation of RAS signal transduction, RAS-altered metabolism, and the associated immune microenvironment. This study reviews the mechanisms and efficacy of novel targeted therapies for different RAS mutants, including KRAS allele-specific inhibitors, combination therapies, immunotherapies, and metabolism-associated therapies.

Liver fibrosis therapy based on biomimetic nanoparticles which deplete activated hepatic stellate cells.

Liver fibrosis is one of the most common liver diseases with substantial morbidity and mortality. However, effective therapy for liver fibrosis is still lacking. Considering the key fibrogenic role of activated hepatic stellate cells (aHSCs), here we reported a strategy to deplete aHSCs by inducing apoptosis as well as quiescence. Therefore, we engineered biomimetic all-trans retinoic acid (ATRA) loaded PLGA nanoparticles (NPs). HSC (LX2 cells) membranes, presenting the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were coated on the surface of the nanoparticles, while the clinically approved agent ATRA with anti-fibrosis ability was encapsulated in the inner core. The biomimetic coating of TRAIL-expressing HSC membranes does not only provide homologous targeting to HSCs, but also effectively triggers apoptosis of aHSCs. ATRA could induce quiescence of activated fibroblasts. While TM-NPs (i.e. membrane coated NPs without ATRA) and ATRA/NPs (i.e. non-coated NPs loaded with ATRA) only showed the ability to induce apoptosis and decrease the α-SMA expression in aHSCs, respectively, TM-ATRA/NPs induced both apoptosis and quiescence in aHSCs, ultimately leading to improved fibrosis amelioration in both carbon tetrachloride-induced and methionine and choline deficient L-amino acid diet induced liver fibrosis mouse models. We conclude that biomimetic TM-ATRA/NPs may provide a novel strategy for effective antifibrosis therapy.

Single-Molecule Dendritic MRI Nanoprobes Reveal the Size-Dependent Tumor Entrance.

The tumor entrance of drug delivery systems, including therapeutic proteins and nanomedicine, plays an essential role in affecting the treatment outcome. Nanoparticle size is a critical but contradictory factor in making a trade-off among blood circulation, tumor accumulation, and penetration. Here, this work designs a series of single-molecule gadolinium (Gd)-based magnetic resonance imaging (MRI) nanoprobes with well-defined sizes to precisely explore the size-dependent tumor entrance in vivo. The MRI nanoprobes obtained by divergent synthesis contain a core molecule of macrocyclic Gd(III)-chelate and different layers of dendritic lysine units, mimicking globular protein. This work finds that the r1 relaxivity and MR imaging signals increase with the nanoparticle size. The nanoprobe with a lower limit of critical size threshold ≈8.0 nm achieves superior tumor accumulation and penetration. These single-molecule MRI nanoprobes can be served to precisely examine the size-related nanoparticle-biological interactions.