Biological Barriers Research Articles

Toxic effects of microplastic and nanoplastic on the reproduction of teleost fish in aquatic environments.

Microplastics and nanoplastics are widely present in aquatic environments and attract significant scholarly attention due to their toxicity, persistence, and ability to cross biological barriers, which pose substantial risks to various fish species. Microplastics and nanoplastics can enter fish through their digestive tract, gills and skin, causing oxidative damage to the body and adversely affecting their reproductive system. Given that fish constitute a crucial source of high-quality protein for humans, it is necessary to study the impact of microplastics on fish reproduction in order to assess the impact of pollutants on ecology, biodiversity conservation, environmental sustainability, and endocrine disruption. This review explores the reproductive consequences of microplastics and nanoplastics in fish, examining aspects such as fecundity, abnormal offspring, circadian rhythm, gonad index, spermatocyte development, oocyte development, sperm quality, ovarian development, and changes at the molecular and cellular level. These investigations hold significant importance in environmental toxicology.

Transcytosable and Ultrasound-Activated Liposome Enables Deep Penetration of Biofilm for Surgical Site Infection Management.

Biofilm-associated surgical site infection (BSSI) is a common and grievous postoperative complication lacking effective remedies, mainly due to the poor drug accumulation and penetration in the biofilms featured by dense extracellular polymeric substances (EPSs). Here, it is found that the vascular cell adhesion molecule-1 (VCAM1) is highly overexpressed in the vascular cells of BSSI. It is proposed that the combination of VCAM1-mediated transcytosis and ultrasonic cavitation can consecutively overcome the biological barriers of vascular endothelial cells and EPS for biofilm eradication. To demonstrate the feasibility, a VCAM1-targeted and ultrasound (US)-activated liposome (LPCOTML) loaded with a reactive-oxygen-species (ROS)-responsive lipoid prodrug of oleoyl meropenem, sonosensitizer of lipoid Ce6, and perfluoropentane is developed. LPCOTML can recognize the receptors on vascular cells, and initiate receptor-mediated transcytosis for transendothelial transport into the BSSI periphery. LPCOTML subsequently transforms from nanoparticle into microbubble via liquid-gas phase transition under US irradiation, triggering strong ultrasonic cavitation to blow up the EPS and deeply penetrate the biofilms. The sonosensitizer Ce6 induces ROS production under US irradiation and triggers the release of meropenem to induce potent antibacterial effect in a BSSI model. This study presents an effective strategy to tackle the biological barriers in BSSI via combining receptor-mediated transcytosis and ultrasonic cavitation.

Adeno‐associated virus vectors for gene therapy—focusing on melanoma

AbstractAdeno‐Associated Virus (AAV) vectors have been found to have great potential in the field of gene therapy due to their unique properties. These nonpathogenic vectors exhibit high tissue specificity, low immunogenicity, and sustained gene expression, enhancing their efficacy for targeted delivery. This review explores the application of AAV vectors in gene therapy. It introduces the application and development of AAV in hemophilia and Duchenne Muscular Dystrophy. The review also highlights the use of AAV vectors in melanoma gene therapy, focusing on four key areas: cancer growth intervention, targeting cancer cells, mediating immune responses, and modulating key signaling pathways. However, despite its many advantages, rAAV faces significant challenges, including host immune responses and biological barriers that limit its effectiveness. Such complexities need to be addressed; therefore, this review also discusses the application of several polymers, such as hydrogels, nanoparticles, and solid scaffolds, in the controlled delivery of AAV.

Synthesis of Nanoparticles for Drug Delivery in Korea

Purpose: The aim of the study was to assess the synthesis of nanoparticles for drug delivery in Korea. Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: The study indicated that the synthesis of nanoparticles for drug delivery has emerged as a promising strategy to enhance the efficacy and precision of therapeutic interventions. Nanoparticles offer several advantages, such as improved bioavailability, targeted delivery, and controlled release of drugs. Various methods are employed in their synthesis, including chemical reduction, sol-gel processes, and biological methods using natural organisms. These nanoparticles can be engineered to carry a wide range of drugs, including chemotherapeutics, antibiotics, and vaccines. Their small size allows them to navigate biological barriers and deliver drugs directly to specific tissues or cells, reducing side effects and improving treatment outcomes. However, challenges such as scalability, toxicity, and regulatory hurdles remain, necessitating further research to optimize their clinical applications. Implications to Theory, Practice and Policy: Brownian motion theory, nanoscale phenomena theory, thermodynamic theory of nanoparticle stability may be used to anchor future studies on the synthesis of nanoparticles for drug delivery in Korea. Practitioners in the field should prioritize the enhancement of synthesis techniques and the focus on biocompatibility and safety to improve the practical applications of nanoparticle drug delivery systems. To ensure the safe and effective use of nanoparticles in drug delivery, policymakers must establish clear guidelines and regulations governing their application.

Nuclear-Targeting Peptides for Cancer Therapy.

Nucleus is the central regulator of cells that controls cell proliferation, metabolism, and cell cycle, and is considered the most important organelle in cells. The precision medicine that can achieve nuclear targeting has achieved good therapeutic effects in anti-tumor therapy. However, the presence of biological barriers such as cell membranes and nuclear membranes in cells limit the delivery of therapeutic agents to the nucleus. Therefore, developing effective nuclear-targeting drug delivery strategies is particularly important. Nuclear-targeting peptides are a class of functional peptides that can penetrate cell membranes and target the nucleus. They mainly recognize and bind to the nuclear transport molecules (such as Importin-α/β) and transport the therapeutic agents to the nucleus through nuclear pore complexes (NPC). This review summarizes the most recent developments of strategies for anti-tumor therapy utilizing nuclear-targeting peptides, which will ultimately contribute to the development of more effective nuclear-targeting strategies to achieve better anti-tumor outcomes.

Multifunctional hyaluronic acid ligand-assisted construction of CD44- and mitochondria-targeted self-assembled upconversion nanoparticles for enhanced photodynamic therapy.

Upconversion nanoparticles (UCNPs) have been used as a potential nanocarrier for photosensitizers (PSs), which have demonstrated a great deal of promise in achieving an effective photodynamic therapy (PDT) for deep-seated tumors. However, overcoming biological barriers to achieve mitochondria-targeted PDT remains a major challenge. Herein, CD44- and mitochondria-targeted photodynamic nanosystems were fabricated through the self-assembly of hyaluronic acid-conjugated-methoxy poly(ethylene glycol)-diethylenetriamine-grafted-(chlorin e6-dihydrolipoic acid-(3-carboxypropyl)triphenylphosphine bromide) polymeric ligands (HA-c-mPEG-Deta-g-(Ce6-DHLA-TPP)) and NaErF4:Tm@NaYF4 core-shell UCNPs (termed CMPNs). The CMPNs presented ideal physiological stability, a good drug loading capacity and an improved capacity for the generation of singlet oxygen (1O2) based on the FRET mechanism. Significantly, confocal images revealed that CMPNs not only facilitated cellular uptake through CD44-receptor-targeted endocytosis, subsequently enabling rapid evasion from endo-lysosomal sequestration, but also specifically targeted mitochondria, ultimately inducing a profound disruption of mitochondrial membrane potential, which triggered apoptosis upon laser irradiation, thereby significantly enhancing the therapeutic effect. Furthermore, in vitro antitumor experiments further confirmed the substantial enhancement in cancer cell killing efficiency achieved by treating with CMPNs upon near-infrared (NIR) laser irradiation. This innovative approach holds promise for the development of NIR-laser-activated photodynamic nanoagents specifically designed for mitochondria-targeted PDT, thus addressing the limitations of the current PDT treatments.

Vortex Nanodiscs Functionalization to Overcome Macrophage Recognition for Efficient Theragnosis Applications

Biological barriers prevent nanotherapeutics successful accumulation at target cells, limiting diagnosis and treatment responses. Magnetic nanodiscs with a spin‐vortex ground state have shown great promise for magnetomechanical cancer cells annihilation and for neuronal stimulation, requiring very low concentrations for an effective result. However, the biological barriers that these particles encounter upon intravenous administration remain a challenge. Herein, the synthesis of biocompatible multilayered Au/Fe/Au nanodiscs with a spin‐vortex ground state and their inert surface modification is reported. Two different surface modifications with two distinct polyethylene glycol (PEG) molecules are performed, which successfully reduce macrophage uptake, while maintaining the nanodiscs’ biocompatibility. By effectively preventing nanodisc uptake, innovative design features can be rationally incorporated to create a new generation of specific nanotherapeutics by modifying the PEG surface with specific targeting molecules.

Self-Adaptive Magnetic Liquid Metal Microrobots Capable of Crossing Biological Barriers and Wireless Neuromodulation.

Magnetic liquid-bodied microrobots (MRs) possess nearly infinite shape adaptivity. However, they currently confront the risk of structure instability/crushes during shape-morphing in tiny biological environments. This article reports that magnetic liquid metal (LM) MRs (LMMRs) show high structure stability and robust magnetic maneuverability. In this protocol, Fe nanoparticles are encapsulated inside less-than-10-μm LM microdroplets by establishing interfacial chemical potential barriers, yielding LMMRs. Their robust magnetic maneuverability originates from the magnetically controlled assembly of Fe nanoparticles inside LM and distinct liquid-solid interaction. With the self-adaptive shape-recovering capabilities even after 50% deformation, LMMRs can implement vertical climbing over walls up to 400% of its body length and traverse channels with the size of its two-thirds. The in vitro and in vivo experiments have both verified the effective magneto-mechanical stimulation of LMMRs upon neurons after their shape-adaptive crossing the blood-brain barrier under a driven magnetic field. Our work provides a promising strategy for wireless therapies with MRs by safely and effectively overcoming biological barriers.

Advancements in mitochondrial-targeted nanotherapeutics: overcoming biological obstacles and optimizing drug delivery.

In recent decades, nanotechnology has significantly advanced drug delivery systems, particularly in targeting subcellular organelles, thus opening new avenues for disease treatment. Mitochondria, critical for cellular energy and health, when dysfunctional, contribute to cancer, neurodegenerative diseases, and metabolic disorders. This has propelled the development of nanomedicines aimed at precise mitochondrial targeting to modulate their function, marking a research hotspot. This review delves into the recent advancements in mitochondrial-targeted nanotherapeutics, with a comprehensive focus on targeting strategies, nanocarrier designs, and their therapeutic applications. It emphasizes nanotechnology's role in enhancing drug delivery by overcoming biological barriers and optimizing drug design for specific mitochondrial targeting. Strategies exploiting mitochondrial membrane potential differences and specific targeting ligands improve the delivery and mitochondrial accumulation of nanomedicines. The use of diverse nanocarriers, including liposomes, polymer nanoparticles, and inorganic nanoparticles, tailored for effective mitochondrial targeting, shows promise in anti-tumor and neurodegenerative treatments. The review addresses the challenges and future directions in mitochondrial targeting nanotherapy, highlighting the need for precision, reduced toxicity, and clinical validation. Mitochondrial targeting nanotherapy stands at the forefront of therapeutic strategies, offering innovative treatment perspectives. Ongoing innovation and research are crucial for developing more precise and effective treatment modalities.

Ultrasound-Responsive Hydrogel Incorporated with TGF-β Mimetic Peptides for Endometrium Recovery to Restore Fertility.

Unavoidable damage to the basal layer of the endometrium has a huge negative impact on a woman's reproductive health and menstrual cycle. However, it is difficult for medicine to penetrate a series of biological barriers toward the basal layer in the deeper area of the endometrium. To meet this challenge, we developed an ultrasound-responsive hydrogel incorporated with a transforming growth factor-beta (TGF-β) mimetic peptide to enhance pregnancy outcomes by restoring the function of a wounded endometrium due to its deep-tissue-penetration capability. In vitro studies revealed that the TGF-β-mimetic-peptide-loaded hydrogel could achieve 64.35% of cell migration under ultrasound stimulation even in phosphate-buffered saline of pH 6.0. Upon in situ sonication at the uterus, carboxymethyl chitosan can be released from degraded hydrogel to open tight junctions with reduced interstitial pressure by ultrasound to promote deep penetration. Rat studies revealed that the penetration capability of TGF-β-mimetic-peptide-loaded hydrogel with sonication was 1.6 times higher than that of the control group. Besides the rat uterine model, ex vivo human uterine tissue was also collected and imaged, demonstrating up to ∼700 μm of tissue penetration depth. In addition, compared to control groups, effective uterus recovery without intrauterine stenosis and endometrial cavity fluid was observed from rats with severe uterine injury treated by TGF-β-mimetic-peptide-loaded hydrogel. In addition, fertility restoration in the endometrial injury model was observed after treatment with such an ultrasound-responsive hydrogel incorporated with TGF-β mimetic peptides. Overall, this work provides an effective approach to treating endometrial injury for enhanced pregnancy outcomes.

Berberine-Loaded Bovine Serum Albumin Nanoparticles: Fabrication, Characterization, and Drug Release Evaluation

Abstract Introduction/Objective Introduction: Numerous studies have highlighted the diverse biochemical and pharmacological properties of berberine (BER), including its anti-inflammatory, antioxidant, anticancer, and hypolipidemic effects. Nanoparticles play a crucial role in enhancing drug delivery by providing a larger surface area, facilitating quicker dissolution in the bloodstream. Methods/Case Report Methods: Blank bovine serum albumin nanoparticles (BSA NPs) were prepared using a desolvation process, followed by the fabrication of berberine-loaded BSA nanoparticles (BER-NP). Physicochemical characterization, including particle size and zeta potential, was conducted using a Malvern Zetasizer. The mean particle size and distribution were determined using photon correlation spectroscopy (PCS), and transmission electron microscope (TEM) images were obtained for visualization. Fourier transform infrared (FTIR) spectra and differential scanning calorimetry (DSC) thermograms were recorded to assess drug encapsulation efficiency (EE). Berberine release from BER-NPs was evaluated using dialysis membranes. Results (if a Case Study enter NA) Results: FTIR spectra and DSC thermograms confirmed successful drug loading into the nanoparticles. Encapsulation efficiency was determined by UV absorption spectroscopy, revealing high efficiency in the encapsulation process. Dialysis membranes demonstrated controlled release kinetics of berberine from BER-NPs, indicating their potential for targeted drug delivery. Conclusion Conclusion: Berberine-loaded bovine serum albumin nanoparticles exhibit favorable characteristics for drug delivery applications, including enhanced permeation across biological barriers. These nanoparticles hold promise for targeted therapy and combination drug regimens, offering potential benefits for various medical interventions.

Extracellular Vesicle Mobility in Collagen I Hydrogels Is Influenced by Matrix-Binding Integrins.

Extracellular vesicles (EVs) are a diverse population of membrane structures produced and released by cells into the extracellular space for the intercellular trafficking of cargo molecules. They are implicated in various biological processes, including angiogenesis, immunomodulation, and cancer cell signaling. While much research has focused on their biogenesis or their effects on recipient cells, less is understood about how EVs are capable of traversing diverse tissue environments and crossing biological barriers. Their interactions with extracellular matrix components are of particular interest, as such interactions govern diffusivity and mobility, providing a potential basis for organotropism. To start to untangle how EV-matrix interactions affect diffusivity, we use high speed epifluorescence microscopy, single particle tracking, and confocal reflectance microscopy to analyze particle mobility and localization in extracellular matrix-mimicking hydrogels composed of collagen I. EVs are compared with synthetic liposomes and extruded plasma membrane vesicles to better understand the importance of membrane composition on these interactions. By treating EVs with trypsin to digest surface proteins, we determine that proteins are primarily responsible for EV immobilization in collagen I hydrogels. We next use a synthetic peptide competitive inhibitor to narrow down the identity of the proteins involved to argynylglycylaspartic acid (RGD) motif-binding integrins, which interact with unincorporated or denatured nonfibrillar collagen. Moreover, the effect of integrin inhibition with RGD peptides has strong implications for the use of RGD-peptide-based drugs to treat certain cancers, as integrin inhibition appears to increase EV mobility, improving their ability to infiltrate tissue-like environments.

Lung cancer cell-derived exosomes: progress on pivotal role and its application in diagnostic and therapeutic potential.

Lung cancer is frequently detected in an advanced stage and has an unfavourable prognosis. Conventional therapies are ineffective for the treatment of metastatic lung cancer. While certain molecular targets have been identified as having a positive response, the absence of appropriate drug carriers prevents their effective utilization. Lung cancer cell-derived exosomes (LCCDEs) have gained attention for their involvement in the development of cancer, as well as their potential for use in diagnosing, treating, and predicting the outcome of lung cancer. This is due to their biological roles and their inherent ability to transport biomolecules from the donor cells. Lung cancer-associated cell-derived extracellular vesicles (LCCDEVs) have the ability to enhance cell proliferation and metastasis, influence angiogenesis, regulate immune responses against tumours during the development of lung cancer, control drug resistance in lung cancer treatment, and are increasingly recognised as a crucial element in liquid biopsy evaluations for the detection of lung cancer. Therapeutic exosomes, which possess inherent intercellular communication capabilities, are increasingly recognised as effective vehicles for targeted drug delivery in precision medicine for tumours. This is due to their exceptional biocompatibility, minimal immunogenicity, low toxicity, prolonged circulation in the bloodstream, biodegradability, and ability to traverse different biological barriers. Currently, multiple studies are being conducted to create new means of diagnosing and predicting outcomes using LCCDEs, as well as to develop techniques for utilizing exosomes as effective carriers for medication delivery. This paper provides an overview of the current state of lung cancer and the wide range of applications of LCCDEs. The encouraging findings and technologies suggest that the utilization of LCCDEs holds promise for the clinical treatment of lung cancer patients.

Lipid-Based Nanoparticles as Drug Delivery System for Modern Therapeutics.

The emergence of lipid-based nanoparticulate systems has significantly reshaped the landscape of drug delivery. This review aims to encapsulate the advancements, challenges, and potential of lipid-based nanoparticulate drug delivery in modern therapeutics. Lipid-based nanoparticles, including liposomes, lipid nanoparticles, and solid lipid nanoparticles, harness the biocompatibility and biodegradability of lipids to encapsulate and deliver a diverse range of therapeutic agents. This platform offers solutions to various drug delivery challenges, such as enhancing drug solubility and bio- availability, achieving controlled and sustained release, targeted delivery, and co-delivery of multi-agents. These nanoparticles have demonstrated potential in overcoming biological barriers, including the blood-brain barrier, mucosal barriers, and cellular barriers, enabling the delivery of drugs to previously inaccessible sites. Biocompatibility and reduced toxicity are intrinsic attributes of lipid-based nanoparticles, minimizing immune responses and systemic toxicity while promoting personalized medicine possibilities. However, challenges in formulation, stability, and regulatory approval underscore the need for ongoing research and innovation in this field.

A Comprehensive Review of Challenges in Oral Drug Delivery Systems and Recent Advancements in Innovative Design Strategies.

The oral route of drug administration is often preferred by patients and healthcare providers due to its convenience, ease of use, non-invasiveness, and patient acceptance. However, traditional oral dosage forms have several limitations, including low bioavailability, limited drug loading capacity, and stability and storage issues, particularly with solutions and suspensions. Over the years, researchers have dedicated considerable effort to developing novel oral drug delivery systems to overcome these limitations. This review discusses various challenges associated with oral drug delivery systems, including biological, pharmaceutical, and physicochemical barriers. It also explores common delivery approaches, such as gastroretentive drug delivery, small intestine drug delivery, and colon-targeting drug delivery systems. Additionally, numerous strategies aimed at improving oral drug delivery efficiency are reviewed, including solid dispersion, absorption enhancers, lipidbased formulations, nanoparticles, polymer-based nanocarriers, liposomal formulations, microencapsulation, and micellar formulations. Furthermore, innovative approaches like orally disintegrating tablets (ODT), orally disintegrating films (ODF), layered tablets, micro particulates, self-nano emulsifying formulations (SNEF), and controlled release dosage forms are explored for their potential in enhancing oral drug delivery efficiency and promoting patients' compliance. Overall, this review highlights significant progress in addressing challenges in the pharmaceutical industry and clinical settings, offering novel approaches for the development of effective oral drug delivery systems.

Biomimetic Nanoparticles for Basic Drug Delivery.

Biomimetic nanoparticles (BMNPs) are innovative nanovehicles that replicate the properties of naturally occurring extracellular vesicles, facilitating highly efficient drug delivery across biological barriers to target organs and tissues while ensuring maximal biocompatibility and minimal-to-no toxicity. BMNPs can be utilized for the delivery of therapeutic payloads and for imparting novel properties to other nanotechnologies based on organic and inorganic materials. The application of specifically modified biological membranes for coating organic and inorganic nanoparticles has the potential to enhance their therapeutic efficacy and biocompatibility, presenting a promising pathway for the advancement of drug delivery technologies. This manuscript is grounded in the fundamentals of biomimetic technologies, offering a comprehensive overview and analytical perspective on the preparation and functionalization of BMNPs, which include cell membrane-coated nanoparticles (CMCNPs), artificial cell-derived vesicles (ACDVs), and fully synthetic vesicles (fSVs). This review examines both "top-down" and "bottom-up" approaches for nanoparticle preparation, with a particular focus on techniques such as cell membrane coating, cargo loading, and microfluidic fabrication. Additionally, it addresses the technological challenges and potential solutions associated with the large-scale production and clinical application of BMNPs and related technologies.

NIR-Actuated Ferroptosis Nanomotor for Enhanced Tumor Penetration and Therapy.

Ferroptosis nano-inducers have drawn considerable attention in the treatment of malignant tumors. However, low intratumoral hydrogen peroxide level and complex biological barriers hinder the ability of nanomedicines to generate sufficient reactive oxygen species (ROS) and achieve tumor penetration. Here a near-infrared (NIR)-driven ROS self-supplying nanomotor is successfully designed for synergistic tumor chemodynamic therapy (CDT) and photothermal therapy (PTT). Janus nanomotor is created by the asymmetrical modification of polydopamine (PDA) with zinc peroxide (ZnO2) and subsequent ferrous ion (Fe2+) chelation via the polyphenol groups from the PDA, here refer as ZnO2@PDA-Fe (Z@P-F). ZnO2 is capable of slowly releasing hydrogen peroxide (H2O2) into an acidic tumor microenvironment (TME) providing sufficient ingredients for the Fenton reaction necessary for ferroptosis. Upon NIR laser irradiation, the loaded Fe2+ is released and a thermal gradient is simultaneously formed owing to the asymmetric PDA coating, thus endowing the nanomotor with self-thermophoresis based enhanced diffusion for subsequent lysosomal escape and tumor penetration. Therefore, the release of ferrous ions (Fe2+), self-supplied H2O2, and self-thermophoresis of nanomotors with NIR actuation further improve the synergistic CDT/PTT efficacy, showing great potential for active tumor therapy.

PH-sensitive adriamycin hydrochloride and oxaliplatin dual-loaded microspheres synergistically enhance local injections effect of hepatocellular carcinoma

Chemotherapy is the primary palliative treatment for advanced hepatocellular carcinoma (HCC). However, the systemic delivery is associated with the drawbacks including a high risk of adverse effects and a low efficacy. Therefore, local injection therapy may be beneficial. Nevertheless, the existing local drug-carrying microspheres(DOBM)have the characteristics of low loading and abrupt release, can not simultaneously load two drugs, and may cause unnecessary toxicity. In this study, we created the dual-loaded bovine serum albumin (BSA) microspheres (also known as DOBM), which were hollow and contained both oxaliplatin (OXA) and Adriamycin hydrochloride (DOX). In addition, this pH-sensitive drug delivery method exhibited a high drug loading capacity and was promising in breaking through biological barriers, making it a viable option for the treatment of HCC through local implantation. Based on physiochemical evaluation of BSA microspheres, they had a porous structure which was close to the surface. Adriamycin and oxaliplatin were successfully added to the surface of BSA microspheres. According to in vitro experimental results, the growth of human HCC (HCC-LM3 and PLC/PRF/5) cell lines was significantly inhibited by DOBM. Furthermore, in the subcutaneous PLC/PRF/5 HCC model, DOBM played an essential role in tumor development and change in the tumor microenvironment.

Towards a Switchable Nanoparticle Behavior Using Inverse Electron-Demand Diels-Alder Chemistry and Ectoenzyme-Based Ligand Activation

Nanoparticles (NPs) as drug delivery platforms encounter numerous obstacles on their journey from administration to the target site. Often, diametrically opposing particle properties are desirable to overcome biological and physical barriers. Therefore, stimuli-responsive NPs have been developed to allow for specific particle adaptation. In this work, it was demonstrated that NPs can be rendered switchable with respect to their interaction with a receptor through an external chemical stimulus. A combination of the inverse electron-demand Diels-Alder (iEDDA) reaction for subsequent NP functionalization and ectoenzyme-based ligand activation allowed for specific particle tailoring. Building on this, a two-step process for target cell recognition was developed: First, NPs were functionalized with Angiotensin-I (Ang-I) as inactive ligand using iEDDA chemistry. At the target site, the ligand was enzymatically processed to Angiotensin-ll (Ang-II) by cellular ectoenzymes. Ang-ll binds as active ligand to the angiotensin ll type 1 (AT1) receptor on the target cell surface. This enzymatic activation aims to minimize the biological effect of the ligand prior to particle binding, while the NP target cell specificity is increased by a two-step recognition with enzymatic processing and receptor binding.

Advancements in Nanoparticle-Based Precision Drug Delivery: A Review of Development and Optimization for Targeted Therapy in Preclinical Models

In recent years, the widespread adoption of nanoparticles has expanded across a broad spectrum of clinical domains. These nanoparticles have been specifically engineered to address the limitations associated with conventional therapeutics and to navigate various biological barriers—ranging from systemic to cellular levels—that manifest heterogeneity across different patient populations and disease states. The advent of precision treatments, wherein interventions are tailored to individual patients, has contributed to mitigating this variability among patients. Nonetheless, the predominant focus in current nanoparticle research remains on enhancing the uniformity of delivery systems. The realization of precision medicine appears imminent as lipid-based, polymeric, and inorganic nanoparticles are increasingly crafted with heightened precision, facilitating more individualized approaches to medication delivery. In this review, we delve into the advanced designs of nanoparticles employed in both precision and generalized applications, offering insights into their potential to advance precision medicine. Our discussion centers on the innovations in nanoparticle design aimed at overcoming various delivery challenges, suggesting that ingenious nanoparticle engineering holds promise for enhancing performance across a broad spectrum of delivery applications and facilitating tailored designs for specific therapeutic targets, ultimately leading to improved patient outcomes.