Papers, explained in our own words

25. A pH/miR-21 dual-responsive multifunctional DNA tetrahedron for targeted tumor imaging and synergistic chemo-gene therapy

Guo Z, Zhang H, Wang M, Zhang X, Ren X, Wang Y, Et Al.

Small interfering RNA (siRNA) presents promising prospects as a therapeutic agent; its clinical application is constrained by challenges such as inefficient delivery and off-target effects. This study developed a multifunctional DNA Tetrahedron (MDT) platform for synergistic delivery of siRNA and the chemotherapeutic…

• DNA tetrahedron
• Intracellular imaging
• Synergistic therapy
• Tumor targeting

26. Sickle cell disease-specific barriers to in vivo hematopoietic stem cell gene therapy

Choi Rh, Sheehan Va

Gene therapy for individuals living with sickle cell disease is a transformative therapy, ameliorating many of its severe symptoms. Nevertheless, ex vivo administration of gene therapy coupled with sickle cell disease specific obstacles, complicate and limit widespread adoption. In this review, we discuss current…

• Bone marrow
• Gene therapy
• Hematopoietic stem cells
• Sickle cell disease

27. Chemical topology of lipo-amino fatty acid mRNA carriers triggers distinct lipid bulk phases and endosomal escape mechanisms ☆

Grau M, Kostyurina E, Seidl J, Martini N, Winkeljann B, Merkel Om, Et Al.

LAF-Stp xenopeptides (XPs) comprising lipoamino fatty acid (LAF) units connected with the tetraethylene pentamine derived polyamino acid Stp were identified as a novel class of amphiphilic mRNA carriers. A 'chameleon-like' polarity switch is observed upon transition from neutral physiological to endosomal acidic pH…

• Molecular dynamics
• Nanocarriers
• Polyplexes
• SAXS
• Ultrastructure

28. FGFR4 Enhances Extracellular Vesicle-Associated Output and Promotes STAT1-Dependent LGALS3BP Enrichment in Colorectal Cancer

Kim Dh, Choi Jn, Hwang Je, Shim Hj, Bang Hj, Kim Hj, Et Al.

Fibroblast growth factor receptor 4 (FGFR4) contributes to colorectal cancer (CRC) progression, but its effects on extracellular vesicle (EV)-associated proteins remain unclear. In the present study, we examined FGFR4-associated changes in EV-enriched extracellular fractions and the role of STAT1 in LGALS3BP…

• FGFR4
• LGALS3BP
• STAT1
• colorectal cancer
• extracellular vesicles
• secretome
• transcriptome

29. Hydrophobicity-tuned oleic acid-functionalized chitosan nanoparticles for sustained ocular delivery of dapagliflozin in diabetic cataract

Lin Zi, Yeh Tc, Sun Gc, Chen Yy, Cheng Pw

Chitosan-based biological macromolecules provide a versatile platform for ocular drug delivery, but their hydrophilic nature limits the encapsulation and sustained release of hydrophobic therapeutics. Here, we designed oleic acid-functionalized chitosan nanoparticles (OA-CS NPs) with tunable hydrophobicity by varying…

• Chitosan
• Dapagliflozin
• Diabetic cataract
• Epithelial–mesenchymal transition
• Nanoparticles
• Ocular drug delivery

30. Chitosan nanoparticles functionalised with protocatechuic acid improve colon-targeted pazopanib delivery with multi-pathway therapeutic regulation and pharmacokinetic optimisation in colorectal cancer

Maheshwari T, Bhattacharya S

Poor pharmacokinetics, insufficient tumor-selective drug accumulation, and systemic toxicity are often the main obstacles to colorectal cancer (CRC) treatment. Here, protocatechuic acid-functionalized chitosan nanoparticles (PAZ-CS-PCA-NPs) were designed to enhance the pharmacological efficacy of pazopanib via…

• Chitosan nanoparticles
• Colon-targeted drug delivery
• Colorectal cancer
• Cultivable fecal bacteria
• Oxidative stress
• Pazopanib
• Pharmacokinetics
• Protocatechuic acid

31. Enhancing Drug Delivery and Efficacy in Stroke via Supramolecular Nanoparticle Systems

Huang Xy, Xu My, Zhang M, Lu X, Tang Jb, Yan Bc, Et Al.

The pathogenesis of ischemic stroke involves multiple pathological links, such as blood-brain barrier (BBB) disruption, oxidative stress, and neuroinflammation, making comprehensive intervention via a single drug exceedingly difficult. In this study, we constructed a supramolecular coassembly nanoparticles (UA-Gen…

32. Integration of Charged Peptide Amphiphiles within Lipid Nanoparticles (LNPs) for Enhanced Targeted mRNA Delivery

Yuan Y, Li G, Liu Y, Liu L, Hu C, Qi H, Et Al.

Lipid nanoparticles (LNPs) play a pivotal role in mRNA-based therapy; however, achieving targeted delivery remains challenging. We developed an LNP platform integrating peptide amphiphiles (PAs) to exploit their dual bioactivity and electrostatic tunability. Two PAs, cationic C16TAT (derived from a cell-penetrating…

• cell-penetrating peptides
• co-assembly
• lipid nanoparticles
• peptide amphiphiles
• targeted delivery

33. mRNA folding facilitates efficient and spleen-targeted delivery by highly branched poly(β-amino ester)s

Li H, Sun Q, Wang S, Xu W, Shi L, Yang Y, Et Al.

Messenger RNA (mRNA)-based therapeutics hold great promise in preventing and treating various diseases. However, the instability and high immunogenicity of raw mRNA molecules, along with the inefficient delivery vectors, strictly limited the proteins translation and therapeutic applications. In this work, we…

• Folded structural mRNA
• Highly branched poly(β-amino ester)s
• Mg(2+)-mediated mRNA folding
• Spleen-targeted delivery
• mRNA delivery

34. Transcription activator-like effector base editing delivered by a targeted lipid nanoparticle for therapy of lung cancer

Chen Y, Li P, Xie Y, Wujieti B, Cui W, Zhang H, Et Al.

Lung cancer is the leading cause of cancer-related deaths worldwide. Among them, non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases, while the mutation of KRAS oncogene plays a crucial role in its formation and metastasis. Here, we report a transcription activator-like effector (TALE) base…

• Gene editing
• KRAS oncogene
• NSCLC
• TALE base editor
• Targeted LNP

35. Optical Manipulation-Assisted Three-Dimensional Single-Particle Tracking Reveals Extracellular Vesicle-Cell Real-Time Interactions In Vitro

Wang C, Huang M, Zhang Y, Chen X, Li S, Chen Q, Et Al.

Extracellular vesicles (EVs) play essential roles in intercellular communication and are promising nanocarriers for drug delivery. Directly resolving the three-dimensional (3D) dynamics of EVs during their interactions with target cells can provide critical insights and help guide the rational design of EV-based…

• double-helix point spread function
• dynamic uptake
• extracellular vesicles
• optical tweezers
• single-particle tracking

36. Targeted delivery of celastrol and siRNA via macrophage biomimetic nanoparticles for doxorubicin-induced cardiomyopathy therapy

Zhang Q, Guo T, Xue X, Zhang Z, Liu X, Cai Q, Et Al.

Doxorubicin-induced cardiomyopathy (DIC) is a severe complication following anthracycline chemotherapy, and its main pathogenesis is inflammatory responses and ferroptosis. This study constructed hyaluronic acid-based macrophage biomimetic nanoparticles (M@HCDA) to co-delivery of Celastrol (Cel) and siADAM17 for the…

• ADAM17
• Biomimetic nanoparticle
• Celastrol
• Doxorubicin-induced cardiomyopathy
• Inflammation/ferroptosis

37. A dual-targeting lipid nanoparticle delivery system for precision phage therapy against multidrug-resistant Gram-negative bacteria

Chen Z, Hu W, Nie H, Zhang Y, Tang W, Yu Z, Et Al.

The escalating crisis of antimicrobial resistance, particularly among Gram-negative bacteria, demands innovative therapeutic strategies. Here, we present a dual-targeting lipid nanoparticle-chimeric phage (AbLCP) system engineered to combat multidrug-resistant (MDR) Gram-negative bacteria. Our design integrates a…

38. Laser-responsive chitosan-coated solid lipid nanoparticles co-encapsulating CaO 2 nanoparticles and IR780 for on-demand and enhanced photodynamic therapy of cancers

Amiri M, Heydari E, Esmaeili M, Zare-Behtash H, Moeini M

The photodynamic therapy (PDT) efficacy is limited by tumor hypoxia and inefficient intracellular accumulation of photosensitizers (PSs). This study reports chitosan-coated solid lipid nanoparticles (SLNs) co-encapsulating the near-infrared photosensitizer IR780 and oxygen-generating CaO 2 nanoparticles (NPs) for…

• Chitosan
• Light-responsive
• Oxygen release
• Photodynamic therapy
• Solid lipid nanoparticles

39. Redox-Induced Polymeric Micelle-to-Coacervate Transition for Enhanced Endosomal Escape, Prolonged Drug Retention, and Improved Sequential Drug Delivery

Ying J, Wang J, Liu Z, Chen Y, Nie Y, Huang Y, Et Al.

Polymeric micelles (PMs) and coacervate microdroplets (CMs) are both promising delivery vehicles, yet each suffers from distinct limitations. The delivery efficiency of PMs is often hindered by factors, such as limited endosome escape and uncontrolled drug release. On the other hand, CMs are prone to coalescence and…

40. Near-Infrared Light-Responsive Liposomes for Modulating Switchable CAR-T Cell Therapy

Lu G, Zhang H, Wang H, Gao X, Zhang K, Song Y, Et Al.

Chimeric antigen receptor T (CAR-T) cell therapy has great potential but is limited by off-target effects and cytokine release syndrome. To address these challenges, we developed a mesothelin-targeted switchable CAR-T cell system whose activity can be externally controlled by near-infrared (NIR) light-responsive…

• chimeric antigen receptor T
• liposomes
• mesothelin
• near-infrared light-responsive

41. LNP-mediated CRISPR gene editing of human vascular endothelial cells in 2D and 3D microfluidic cell culture systems

Olsen Al, Brandt Cbv, Larsen Rk, Fonager Sv, Zubia-Aranburu J, Haskó J, Et Al.

Efficient and cell-type-specific delivery remains a major barrier to CRISPR-based genome editing in vascular endothelial cells. Here, we systematically evaluate lipid nanoparticle (LNP)-mediated mRNA and CRISPR delivery in human umbilical vein endothelial cells (HUVECs). While a conventional SM-102-based LNP…

• CRISPR
• Cas9
• LNP
• MT: delivery strategies
• endothelial cells
• endothelium
• genome editing
• lipid nanoparticles
• microfluidics
• microvasculature on a chip

42. Overcoming technological and biological barriers to pulmonary mRNA delivery with lipid-polymer hybrid nanoparticles

Biesel A, Shandheep A, Pavlou A, Busker Lm, Koch M, Kopliku V, Et Al.

Delivering mRNA to the lungs promises treatment of genetic, infectious and non-communicable lung diseases. Yet, conventional lipid nanoparticle formulations lack the stability needed to endure the harsh mechanical stress during nebulization. Additionally, once deposited in the respiratory tract, gene delivery systems…

• DLin-MC3-DMA
• DOTAP
• Lung epithelial cells
• Microfluidics
• Poly(lactic-co-glycolic) acid
• Vibrating mesh nebulization

43. Thermodynamic Model and Experiments Indicate Kinetically Trapped States in Ionisable Lipid Nanoparticles

Kostyurina E, Sudarsan A, Huber M, Westerhausen C, Schwierz N, Raedler J, Et Al.

Lipid nanoparticles (LNPs) are the leading delivery vehicles for RNA-based therapies, with pH-dependent mesophase transitions of their ionizable lipids proposed to play a crucial role in LNP function and endosomal escape. However, a consistent quantitative framework linking molecular lipid properties to the…

44. T cell engineering by targeted small extracellular vesicles delivering CRISPR/Cas9 system for PD-1 knock-out

Farahani Ms, Shamsara M, Moazzeni Sm, Khalili S, Johnson B, Darzi L, Et Al.

Among the emerging cancer therapies, immunotherapy using T cell engineering stands out as one of the most promising approaches. While the clustered regularly interspaced palindromic repeats (CRISPR/Cas) system is widely recognized as one of the most common gene-editing system tools, the main challenge for in vivo…

• PD-1 knock-out
• CRISPR/Cas9
• Gene editing
• T cell
• Targeted small extracellular vesicle

45. Exosome-Coated Dendrimer Nanogels as a Therapeutic Vaccine for CT Imaging-Guided Chemoimmunotherapy of Pancreatic Cancer

Li Z, Xiao X, Li Y, Qin M, Xia L, Yang J, Et Al.

Development of new medicines that can treat pancreatic cancer with a sustained immune memory effect remains to be a challenging task. Herein, we report a tumor microenvironment-responsive dendrimer nanogel (DNG)-based therapeutic vaccine co-loaded with toyocamycin (Toy) and gold nanoparticles (Au NPs) and the surface…

• chemoimmunotherapy
• dendrimer nanogels
• exosomes
• immunogenic cell death
• pancreatic cancer

46. Formulation optimisation of an mRNA-lipid nanoparticle platform sustains in vivo production of the SARS-CoV-2-neutralizing nanobody VHH 72

Dong Y, Li Q, Ou Y, Li M, Liu N, Wang X, Et Al.

Neutralizing antibodies act rapidly against SARS-CoV-2, but monoclonal antibodies are costly to manufacture and single-domain antibodies are cleared rapidly. Here we evaluated an mRNA-lipid nanoparticle (LNP) platform encoding the neutralizing nanobody VHH 72 and optimized the carrier by raising DSPC from 10 to 40…

• Formulation optimization
• Lipid nanoparticle
• Nanobody
• SARS-CoV-2
• Sustained expression
• mRNA delivery

47. Comparison of Wildtype and Recombinant Adeno-Associated Virus (AAV) Production Reveals Distinct Productivity and Content Ratio Profiles

Alfieri S, Lee Kh

Recombinant adeno-associated virus is a leading viral vector for gene therapy. However, recombinant adeno-associated virus production systems have low titer and content ratio (ratio of genome-containing to total adeno-associated virus capsids), making it difficult to generate the large number of vector genomes…

• content ratio
• gene therapy
• recombinant adeno‐associated virus (rAAV)
• transient transfection
• viral vector manufacturing
• wildtype AAV infection

48. Simple heat-assisted method for mRNA loading into empty lipid nanoparticles enables robust in vitro and in vivo delivery

Miyazaki T, Kubara K, Kondo K, Kamiyama H, Hara S, Moriya J, Et Al.

mRNA-lipid nanoparticles (LNP) have emerged as a versatile modality, enabling diverse applications by changing encoded mRNA sequences. However, the conventional mRNA-LNP preparation process poses significant barriers to non-specialists because it requires specialized equipment and technical expertise. In this study…

• 96-well compatible
• Homogeneity
• Lipid nanoparticle
• Post-encapsulation
• Technical barriers
• mRNA