Biology-Inspired Nanomaterials Research Articles

Insights into the formulation of lipid nanoparticles for the optimization of mRNA therapeutics.

mRNA-based therapeutics increasingly demonstrate significant potential in treating various diseases, including infectious diseases, cancers, and genetic disorders. Effective delivery systems are crucial for advancing mRNA therapeutics. Lipid nanoparticles (LNPs) serve as an excellent carrier, widely validated for their safety and tolerability in commercially available mRNA vaccines. Standard LNPs typically consist of four components: ionizable lipids (ILs), helper lipids, cholesterol, and polyethylene glycol-lipids (PEG-lipids), with the structural design of ILs gradually becoming a focal point of research interest. The chemical structures and formulations of the other components also significantly affect the delivery efficiency, targeting specificity, and stability of LNPs. The complex formulations of LNPs may hinder the clinical transformation of mRNA therapeutics and have raised widespread concerns about their safety. This review aims to summarize the progress of LNPs-based mRNA therapeutics in clinical trials, focusing on adverse effects that occurred during these trials. It also discusses representative innovations in LNP components, highlighting challenges and potential ways in this research field. We firmly believe this review will promote further improvements and designs of LNP compositions to optimize mRNA therapeutics. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures.

Bioactive poly(amino acid)s for multi-modal cancer therapy.

The interplay between the tumor cells and their microenvironments is as inseparable as the relationship between "seeds" and "soil." The tumor microenvironments (TMEs) exacerbate malignancy by enriching malignant cell subclones, generating extracellular matrices, and recruiting immunosuppressive cells, thereby diminishing the efficacy of clinical therapies. Modulating TMEs has emerged as a promising strategy to enhance cancer therapy. However, the existing drugs used in clinical settings do not target the TMEs specifically, underscoring the urgent need for advanced strategies. Bioactive materials present unique opportunities for modulating TMEs. Poly(amino acid)s with precisely controllable structures and properties offer exceptional characteristics, such as diverse structural units, excellent biosafety, ease of modification, sensitive biological responsiveness, and unique secondary structures. These attributes hold significant potential for the modulation of TMEs and clinical applications further. Consequently, developing bioactive poly(amino acid)s capable of modulating the TMEs by elucidating structure-activity relationships and mechanisms is a promising approach for innovative clinical oncology therapy. This review summarizes the recent progress of our research team in developing bioactive poly(amino acid)s for multi-modal tumor therapy. First, a brief overview of poly(amino acid) synthesis and their advantages as nanocarriers is provided. Subsequently, the pioneering research of our research group on synthesizing the biologically responsive, dynamically allosteric, and immunologically effective poly(amino acid)s are highlighted. These poly(amino acid)s are designed to enhance tumor therapy by modulating the intracellular, extracellular matrix, and stromal cell microenvironments. Finally, the future development of poly(amino acid)s is discussed. This review will guide and inspire the construction of bioactive poly(amino acid)s with promising clinical applications in cancer therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology-Inspired Nanomaterials > Peptide-Based Structures.

Manipulation of protein corona for nanomedicines.

Nanomedicines have significantly advanced the development of diagnostic and therapeutic strategies for various diseases, while they still encounter numerous challenges. Upon entry into the human body, nanomedicines interact with biomolecules to form a layer of proteins, which is defined as the protein corona that influences the biological properties of nanomedicines. Traditional approaches have primarily focused on designing stealthy nanomedicines to evade biomolecule adsorption; however, due to the intricacies of the biological environment within body, this method cannot completely prevent biomolecule adsorption. As research on the protein corona progresses, manipulating the protein corona to modulate the in vivo behaviors of nanomedicines has become a research focus. In this review, modern strategies focused on influencing the biological efficacy of nanomedicines in vivo by manipulating protein corona, along with their wide-ranging applications across diverse diseases are critically summarized, highlighted and discussed. Finally, future directions for this important yet challenging research area are also briefly discussed. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

Nanotechnology-driven strategies to enhance the treatment of drug-resistant bacterial infections.

The misuse of antibiotics has led to increased bacterial resistance, posing a global public health crisis and seriously endangering lives. Currently, antibiotic therapy remains the most common approach for treating bacterial infections, but its effectiveness against multidrug-resistant bacteria is diminishing due to the slow development of new antibiotics and the increase of bacterial drug resistance. Consequently, developing new a\ntimicrobial strategies and improving antibiotic efficacy to combat bacterial infection has become an urgent priority. The emergence of nanotechnology has revolutionized the traditional antibiotic treatment, presenting new opportunities for refractory bacterial infection. Here we comprehensively review the research progress in nanotechnology-based antimicrobial drug delivery and highlight diverse platforms designed to target different bacterial resistance mechanisms. We also outline the use of nanotechnology in combining antibiotic therapy with other therapeutic modalities to enhance the therapeutic effectiveness of drug-resistant bacterial infections. These innovative therapeutic strategies have the potential to enhance bacterial susceptibility and overcome bacterial resistance. Finally, the challenges and prospects for the application of nanomaterial-based antimicrobial strategies in combating bacterial resistance are discussed. This article is categorized under: Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

The application strategy of liposomes in organ targeting therapy.

Liposomes-microscopic phospholipid bubbles with bilayered membrane structure-have been a focal point in drug delivery research for the past 30 years. Current liposomes possess a blend of biocompatibility, drug loading efficiency, prolonged circulation and targeted delivery. Tailored liposomes, varying in size, charge, lipid composition, and ratio, have been developed to address diseases in specific organs, thereby enhancing drug circulation, accumulation at lesion sites, intracellular delivery, and treatment efficacy for various organ-specific diseases. For further successful development of this field, this review summarized liposomal strategies for targeting different organs in series of major human diseases, including widely studied cardiovascular diseases, liver and spleen immune diseases, chronic or acute kidney injury, neurodegenerative diseases, and organ-specific tumors. It highlights recent advances of liposome-mediated therapeutic agent delivery for disease intervention and organ rehabilitation, offering practical guidelines for designing organ-targeted liposomes. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures.

An overview of lipid constituents in lipid nanoparticle mRNA delivery systems.

mRNA therapeutics have shown great potential for a broad spectrum of disease treatment. However, the challenges of mRNA's inherent instability and difficulty in cellular entry have hindered its progress in the biomedical field. To address the cellular barriers and deliver mRNA to cells of interest, various delivery systems are designed. Among these, lipid nanoparticles (LNPs) stand out as the most extensively used mRNA delivery systems, particularly following the clinical approvals of corona virus disease 2019 (COVID-19) mRNA vaccines. LNPs are comprised of ionizable cationic lipids, phospholipids, cholesterol, and polyethylene glycol derived lipids (PEG-lipids). In this review, we primarily summarize the recent advancements of the LNP mRNA delivery technology, focusing on the structures of four lipid constituents and their biomedical applications. We delve into structure-activity relationships of the lipids, while also exploring the future prospects and challenges in developing more efficacious mRNA delivery systems. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

DNA nanostructures as biomolecular scaffolds for antigen display.

Nanoparticle-based vaccines offer a multivalent approach for antigen display, efficiently activating T and B cells in the lymph nodes. Among various nanoparticle design strategies, DNA nanotechnology offers an innovative alternative platform, featuring high modularity, spatial addressing, nanoscale regulation, high functional group density, and lower self-antigenicity. This review delves into the potential of DNA nanostructures as biomolecular scaffolds for antigen display, addressing: (1) immunological mechanisms behind nanovaccines and commonly used nanoparticles in their design, (2) techniques for characterizing protein NP-antigen complexes, (3) advancements in DNA nanotechnology and DNA-protein assembly approach, (4) strategies for precise antigen presentation on DNA scaffolds, and (5) current applications and future possibilities of DNA scaffolds in antigen display. This analysis aims to highlight the transformative potential of DNA nanoscaffolds in immunology and vaccinology. This article is categorized under: Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

Recent developments in the use of centrifugal spinning and pressurized gyration for biomedical applications.

Centrifugal spinning is a technology used to generate small diameter fibers and has been extensively studied for its vast applications in biomedical engineering. Centrifugal spinning is known for its rapid production rate and has inspired the creation of other technologies which leverage the high-speed rotation, namely Pressurized Gyration. Pressurized gyration incorporates a unique applied gas pressure which serves to provide additional control over the fiber production process. The resulting fibers are uniquely suitable for a range of healthcare-related applications that are thoroughly discussed in this work, which involve scaffolds for tissue engineering, solid dispersions for drug delivery, antimicrobial meshes for filtration and bandage-like fibrous coverings for wound healing. In this review, the notable recent developments in centrifugal spinning and pressurized gyration are presented and how these technologies are being used to further the range of uses of biomaterials engineering, for example the development of core-sheath fabrication techniques for multi-layered fibers and the combination with electrospinning to produce advanced fiber mats. The enormous potential of these technologies and their future advancements highlights how important they are in the biomedical discipline. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures.

Transferosomes as a transdermal drug delivery system: Dermal kinetics and recent developments.

The development of innovative approaches to deliver medications has been growing now for the last few decades and generates a growing interest in the dermatopharmaceutical field. Transdermal drug delivery in particular, remains an attractive alternative route for many therapeutics. However, due to the limitations posed by the barrier properties of the stratum corneum, the delivery of many pharmaceutical dosage forms remains a challenge. Most successful therapies using the transdermal route have been ones containing smaller lipophilic molecules with molecular weights of a few hundred Daltons. To overcome these limitations of size and lipophilicity of the drugs, transferosomes have emerged as a successful tool for transdermal delivery of a variety of therapeutics including hydrophilic actives, larger molecules, peptides, proteins, and nucleic acids. Transferosomes exhibit a flexible structure and higher surface hydrophilicity which both play a critical role in the transport of drugs and other solutes using hydration gradients as a driving force to deliver the molecules into and across the skin. This results in enhanced overall permeation as well as controlled release of the drug in the skin layers. Additionally, the physical-chemical properties of the transferosomes provide increased stability by preventing degradation of the actives by oxidation, light, and temperature. Here, we present the history of transferosomes from solid lipid nanoparticles and liposomes, their physical-chemical properties, dermal kinetics, and their recent advances as marketed dosage forms. This article is categorized under: Biology-Inspired Nanomaterials > Lipid-Based Structures Therapeutic Approaches and Drug Discovery > Emerging Technologies.

The clinical progress and challenges of mRNA vaccines.

Owing to the breakthroughs in the prevention and control of the COVID-19 pandemic, messenger RNA (mRNA)-based vaccines have emerged as promising alternatives to conventional vaccine approaches for infectious disease prevention and anticancer treatments. Advantages of mRNA vaccines include flexibility in designing and manipulating antigens of interest, scalability in rapid response to new variants, ability to induce both humoral and cell-mediated immune responses, and ease of industrialization. This review article presents the latest advances and innovations in mRNA-based vaccines and their clinical translations in the prevention and treatment of infectious diseases or cancers. We also highlight various nanoparticle delivery platforms that contribute to their success in clinical translation. Current challenges related to mRNA immunogenicity, stability, and in vivo delivery and the strategies for addressing them are also discussed. Finally, we provide our perspectives on future considerations and opportunities for applying mRNA vaccines to fight against major infectious diseases and cancers. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Lipid-Based Structures.

Gene-encoded nanoparticle vaccine platforms for in vivo assembly of multimeric antigen to promote adaptive immunity.

Nanoparticle vaccines are a diverse category of vaccines for the prophylaxis or treatment of various diseases. Several strategies have been employed for their optimization, especially to enhance vaccine immunogenicity and generate potent B-cell responses. Two major modalities utilized for particulate antigen vaccines include using nanoscale structures for antigen delivery and nanoparticles that are themselves vaccines due to antigen display or scaffolding-the latter of which we will define as "nanovaccines." Multimeric antigen display has a variety of immunological benefits compared to monomeric vaccines mediated through potentiating antigen-presenting cell presentation and enhancing antigen-specific B-cell responses through B-cell activation. The majority of nanovaccine assembly is done in vitro using cell lines. However, in vivo assembly of scaffolded vaccines potentiated using nucleic acids or viral vectors is a burgeoning modality of nanovaccine delivery. Several advantages to in vivo assembly exist, including lower costs of production, fewer production barriers, as well as more rapid development of novel vaccine candidates for emerging diseases such as SARS-CoV-2. This review will characterize the methods for de novo assembly of nanovaccines in the host using methods of gene delivery including nucleic acid and viral vectored vaccines. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Biology-Inspired Nanomaterials > Protein and Virus-Based Structures Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Multifunctional plant virus nanoparticles: An emerging strategy for therapy of cancer.

Cancer therapy requires sophisticated treatment strategies to obtain the highest success. Nanotechnology is enabling, revolutionizing, and multidisciplinary concepts to improve conventional cancer treatment modalities. Nanomaterials have a central role in this scenario, explaining why various nanomaterials are currently being developed for cancer therapy. Viral nanoparticles (VNPs) have shown promising performance in cancer therapy due to their unique features. VNPs possess morphological homogeneity, ease of functionalization, biocompatibility, biodegradability, water solubility, and high absorption efficiency that are beneficial for cancer therapy applications. In the current review paper, we highlight state-of-the-art properties and potentials of plant viruses, strategies for multifunctional plant VNPs formulations, potential applications and challenges in VNPs-based cancer therapy, and finally practical solutions to bring potential cancer therapy one step closer to real applications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

Magnetically-activated lipid nanocarriers in biomedical applications: A review of current status and perspective.

Magnetically-activated lipid nanocarriers have become a research hotspot in the field of biomedicine. Liposomes and other lipid-based carriers possess good biocompatibility as well as the ability to carrying therapeutic cargo with a range of physicochemical properties. Previous studies have demonstrated that magnetic materials have potential wide applications in clinical diagnosis and therapy, such as in MRI as contrast agents and in hyperthermic obliteration of cancer tissues. More recently magneto-thermal activation of lipid carriers to stimulate drug release has extended the range of further therapeutic benefits. Here, an overview ofthe current development of magnetically-activated lipid nanocarriers in the field of biomedicine is provided, including the methods of fabrication of the nanocarriers and their in vitro and in vivo performance. A discussion of the current barriers to translation of these materials as medicines is provided in the context of clinical and regulatory complexities of using magnetically responsive materials in therapeutic applications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures Implantable Materials and Surgical Technologies > Nanomaterials and Implants.

Protein cargo encapsulation by virus-like particles: Strategies and applications.

Viruses and the recombinant protein cages assembled from their structural proteins, known as virus-like particles (VLPs), have gained wide interest as tools in biotechnology and nanotechnology. Detailed structural information and their amenability to genetic and chemical modification make them attractive systems for further engineering. This review describes the range of non-enveloped viruses that have been co-opted for heterologous protein cargo encapsulation and the strategies that have been developed to drive encapsulation. Spherical capsids of a range of sizes have been used as platforms for protein cargo encapsulation. Various approaches, based on native and non-native interactions between the cargo proteins and inner surface of VLP capsids, have been devised to drive encapsulation. Here, we outline the evolution of these approaches, discussing their benefits and limitations. Like the viruses from which they are derived, VLPs are of interest in both biomedical and materials applications. The encapsulation of protein cargo inside VLPs leads to numerous uses in both fundamental and applied biocatalysis and biomedicine, some of which are discussed herein. The applied science of protein-encapsulating VLPs is emerging as a research field with great potential. Developments in loading control, higher order assembly, and capsid optimization are poised to realize this potential in the near future. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

Nanoparticles for vaccine and gene therapy: Overcoming the barriers to nucleic acid delivery.

Nucleic acid therapeutics can be used to control virtually every aspect of cell behavior and therefore have significant potential to treat genetic disorders, infectious diseases, and cancer. However, while clinically approved to treat a small number of diseases, the full potential of nucleic acid therapeutics is hampered by inefficient delivery. Nucleic acids are large, highly charged biomolecules that are sensitive to degradation and so the approaches to deliver these molecules differ significantly from traditional small molecule drugs. Current studies suggest less than 1% of the injected nucleic acid dose is delivered to the target cell in an active form. This inefficient delivery increases costs and limits their use to applications where a small amount of nucleic acid is sufficient. In this review, we focus on two of the major barriers to efficient nucleic acid delivery: (1) delivery to the target cell and (2) transport to the subcellular compartment where the nucleic acids are therapeutically active. We explore how nanoparticles can be modified with targeting ligands to increase accumulation in specific cells, and how the composition of the nanoparticle can be engineered to manipulate or disrupt cellular membranes and facilitate delivery to the optimal subcellular compartments. Finally, we highlight how with intelligent material design, nanoparticle delivery systems have been developed to deliver nucleic acids that silence aberrant genes, correct genetic mutations, and act as both therapeutic and prophylactic vaccines. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Lipid-Based Structures.

Chiral fiber supramolecular hydrogels for tissue engineering.

Tissue engineering (TE), as a new interdisciplinary discipline, aims to develop biological substitutes for repairing damaged tissues and organs. For the success of tissue regeneration, such biomaterials need to support the physiological activities of cells and allow the growth and maturation of tissues. Naturally, this regulation is achieved through the dynamic remodeling of the extracellular matrix (ECM) of cells. In recent years, chiral supramolecular hydrogels have shown higher application potential in the TE field than traditional polymer hydrogels due to their dynamic noncovalent interactions, adjustable self-assembly structure, and good biocompatibility. These advantages make it possible to construct hydrogels under physiological conditions with structure and function similar to those of the natural ECM. Meanwhile, the chiral characteristics of hydrogels play an important role in regulating cellular activities such as differentiation, adhesion, and proliferation, which is beneficial for tissue formation. In this review, a brief introduction is presented to highlight the importance of chiral fiber supramolecular hydrogels for TE at first. Afterward, the considerations for chiral supramolecular hydrogel design, as well as the influence of external stimuli on chiral hydrogel construction, are discussed. Finally, the potential application prospects of these materials in TE and the significant contribution made by our group in this field are summarized. This review not only helps to reveal the importance of chiral properties in TE but also provides new strategies for TE research based on chiral bionic microenvironments. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Biology-Inspired Nanomaterials > Peptide-Based Structures Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Recent advancements in single dose slow-release devices for prophylactic vaccines.

Single dose slow-release vaccines herald a new era in vaccine administration. An ideal device for slow-release vaccine delivery would be minimally invasive and self-administered, making these approaches an attractive alternative for mass vaccination programs, particularly during the time of a pandemic. In this review article, we discuss the latest advances in this field, specifically for prophylactic vaccines able to prevent infectious diseases. Recent studies have found that slow-release vaccines elicit better immune responses and often do not require cold chain transportation and storage, thus drastically reducing the cost, streamlining distribution, and improving efficacy. This promise has attracted significant attention, especially when poor patient compliance of the standard multidose vaccine regimes is considered. Single dose slow-release vaccines are the next generation of vaccine tools that could overcome most of the shortcomings of present vaccination programs and be the next platform technology to combat future pandemics. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

Intelligent design of polymersomes for antibacterial and anticancer applications.

Polymersomes (or polymer vesicles) have attracted much attention for biomedical applications in recent years because their lumen can be used for drug delivery and their coronas and membrane can be modified with a variety of functional groups. Thus, polymersomes are very suitable for improved antibacterial and anticancer therapy. This review mainly highlighted recent advances in the synthetic protocols and design principles of intelligent antibacterial and anticancer polymersomes. Antibacterial polymersomes are divided into three categories: polymersomes as antibiotic nanocarriers, intrinsically antibacterial polymersomes, and antibacterial polymersomes with supplementary means including photothermal and photodynamic therapy. Similarly, the anticancer polymersomes are divided into two categories: polymersomes-based delivery systems and anticancer polymersomes with supplementary means. In addition, the bilateral relationship between bacteria and cancer is addressed, since more and more evidences show that bacteria may cause cancer or promote cancer progression. Finally, prospective on next-generation antibacterial and anticancer polymersomes are discussed. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology-Inspired Nanomaterials > Lipid-Based Structures.

Application of vinyl polymer‐based materials as nucleic acids carriers in cancer therapy

Nucleic acid-based therapies have changed the paradigm of cancer treatment, where conventional treatment modalities still have several limitations in terms of efficacy and severe side effects. However, these biomolecules have a short half-life in vivo, requiring multiple administrations, resulting in severe suffering, discomfort, and poor patient compliance. In the early days of (nano)biotechnology, these problems caused concern in the medical community, but recently it has been recognized that these challenges can be overcome by developing innovative formulations. This review focuses on the use of vinyl polymer-based materials for the protection and delivery of nucleic acids in cancer. First, an overview of the properties of nucleic acids and their versatility as drugs is provided. Then, key information on the achievements to date, the most effective delivery methods, and the evaluation of functionalization approaches (stimulatory strategies) are critically discussed to highlight the importance of vinyl polymers in the new cancer treatment approaches. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures.

Subcellular delivery of lipid nanoparticles to endoplasmic reticulum and mitochondria.

Primarily responsible for the biogenesis and metabolism of biomolecules, endoplasmic reticulum (ER) and mitochondria are gradually becoming the targets of therapeutic modulation, whose physiological activities and pathological manifestations determine the functional capacity and even the survival of cells. Drug delivery systems with specific physicochemical properties (passive targeting), or modified by small molecular compounds, polypeptides, and biomembranes demonstrating tropism for ER and mitochondria (active targeting) are able to reduce the nonselective accumulation of drugs, enhancing efficacy while reducing side effects. Lipid nanoparticles feature high biocompatibility, diverse cargo loading, and flexible structure modification, which are frequently used for subcellular organelle-targeted delivery of therapeutics. However, there is still a lack of systematic understanding of lipid nanoparticle-based ER and mitochondria targeting. Herein, we review the pathological significance of drug selectively delivered to the ER and mitochondria. We also summarize the molecular basis and application prospects of lipid nanoparticle-based ER and mitochondria targeting strategies, which may provide guidance for the prevention and treatment of associated diseases and disorders. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology-Inspired Nanomaterials > Lipid-Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.