Passive Targeting Research Articles

Comparison of passive targeted delivery of inorganic and organic nanocarriers among different types of tumors

In this study, we have considered four types of nanoparticles (NPs): polylactic acid (PLA), gold (Au), calcium carbonate (CaCO3), and silica (SiO2) with similar sizes (TEM: 50-110nm and DLS: 110-140nm) to examine their passive accumulation in three different tumors: colon (CT26), melanoma (B16-F10), and breast (4T1) cancers. Our results demonstrate that each tumor model showed a different accumulation of NPs, in the following order: CT26>B16-F10>4T1. The Au and PLA NPs were evidently characterized by a higher delivery efficiency in case of CT26 tumors compared to CaCO3 and SiO2 NPs. The Au NPs demonstrated the highest accumulation in B16-F10 cells compared to other NPs. These results were verified using SPECT, ex vivo fluorescence bioimaging, direct radiometry and histological analysis. Thus, this work contributes to new knowledge in passive tumor targeting of NPs and can be used for the development of new strategies for delivery of bioactive compounds.

Natural biomimetic nano-system for drug delivery in the treatment of rheumatoid arthritis: a literature review of the last 5 years.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized primarily by synovitis, leading to the destruction of articular cartilage and bone and ultimately resulting in joint deformity, loss of function, and a significant impact on patients' quality of life. Currently, a combination of anti-rheumatic drugs, hormonal drugs, and biologics is used to mitigate disease progression. However, conventional drug therapy has limited bioavailability, and long-term use often leads to drug resistance and toxic side effects. Therefore, exploring new therapeutic approaches for RA is of great clinical importance. Nanodrug delivery systems offer promising solutions to overcome the limitations of conventional drugs. Among them, liposomes, the first nanodrug delivery system to be approved for clinical application and still widely studied, demonstrate the ability to enhance therapeutic efficacy with fewer adverse effects through passive or active targeting mechanisms. In this review, we provide a review of the research progress on the targeting mechanisms of various natural biomimetic nano-delivery systems in RA therapy. Additionally, we predict the development trends and application prospects of these systems, offering new directions for precision treatment of RA.

Construction of lymph nodes-targeting tumor vaccines by using the principle of DNA base complementary pairing to enhance anti-tumor cellular immune response

Tumor vaccines, a crucial immunotherapy, have gained growing interest because of their unique capability to initiate precise anti-tumor immune responses and establish enduring immune memory. Injected tumor vaccines passively diffuse to the adjacent draining lymph nodes, where the residing antigen-presenting cells capture and present tumor antigens to T cells. This process represents the initial phase of the immune response to the tumor vaccines and constitutes a pivotal determinant of their effectiveness. Nevertheless, the granularity paradox, arising from the different requirements between the passive targeting delivery of tumor vaccines to lymph nodes and the uptake by antigen-presenting cells, diminishes the efficacy of lymph node-targeting tumor vaccines. This study addressed this challenge by employing a vaccine formulation with a tunable, controlled particle size. Manganese dioxide (MnO2) nanoparticles were synthesized, loaded with ovalbumin (OVA), and modified with A50 or T20 DNA single strands to obtain MnO2/OVA/A50 and MnO2/OVA/T20, respectively. Administering the vaccines sequentially, upon reaching the lymph nodes, the two vaccines converge and simultaneously aggregate into MnO2/OVA/A50-T20 particles through base pairing. This process enhances both vaccine uptake and antigen delivery. In vitro and in vivo studies demonstrated that, the combined vaccine, comprising MnO2/OVA/A50 and MnO2/OVA/T20, exhibited robust immunization effects and remarkable anti-tumor efficacy in the melanoma animal models. The strategy of controlling tumor vaccine size and consequently improving tumor antigen presentation efficiency and vaccine efficacy via the DNA base-pairing principle, provides novel concepts for the development of efficient tumor vaccines.Graphical

Photodynamically Tumor Vessel Destruction Amplified Tumor Targeting of Nanoparticles for Efficient Chemotherapy.

Efficient tumor-targeted drug delivery is still a challenging and currently unbreakable bottleneck in chemotherapy for tumors. Nanomedicines based on passive or active targeting strategy have not yet achieved convincing chemotherapeutic benefits in the clinic due to the tumor heterogeneity. Inspired by the efficient inflammatory-cell recruitment to acute clots, we constructed a two-component nanosystem, which is composed of an RGD-modified pyropheophorbide-a (Ppa) micelle (PPRM) that mediates the tumor vascular-targeted photodynamic reaction to activate local coagulation and subsequently transmits the coagulation signals to the circulating clot-targeted CREKA peptide-modified camptothecin (CPT)-loaded nanodiscs (CCNDs) for amplifying tumor targeting. PPRM could effectively bind with the tumor vasculature and induce sufficient local thrombus by a photodynamic reaction. Local photodynamic reaction-induced tumor target amplification greatly increased the tumor accumulation of CCND by 4.2 times, thus significantly enhancing the chemotherapeutic efficacy in the 4T1 breast tumor model. In other words, this study provides a powerful platform to amplify tumor-specific drug delivery by taking advantage of the efficient crosstalk between the PPRM-activated coagulation cascade and clot-targeted CCND.

Nanoparticles for efficient drug delivery and drug resistance in glioma: New perspectives.

Gliomas are the most common primary tumors of the central nervous system, with glioblastoma multiforme (GBM) having the highest incidence, and their therapeutic efficacy depends primarily on the extent of surgical resection and the efficacy of postoperative chemotherapy. The role of the intracranial blood-brain barrier and the occurrence of the drug-resistant gene O6-methylguanine-DNA methyltransferase have greatly limited the efficacy of chemotherapeutic agents in patients with GBM and made it difficult to achieve the expected clinical response. In recent years, the rapid development of nanotechnology has brought new hope for the treatment of tumors. Nanoparticles (NPs) have shown great potential in tumor therapy due to their unique properties such as light, heat, electromagnetic effects, and passive targeting. Furthermore, NPs can effectively load chemotherapeutic drugs, significantly reduce the side effects of chemotherapeutic drugs, and improve chemotherapeutic efficacy, showing great potential in the chemotherapy of glioma. In this article, we reviewed the mechanisms of glioma drug resistance, the physicochemical properties of NPs, and recent advances in NPs in glioma chemotherapy resistance. We aimed to provide new perspectives on the clinical treatment of glioma.

False alarm suppressing for passive underwater acoustic target detecting with computer visual techniques

False alarm suppressing for passive underwater acoustic target detecting with computer visual techniques

Microfluidics-mediated Liposomal Nanoparticles for Cancer Therapy: Recent Developments on Advanced Devices and Technologies.

Liposomes, spherical particles with phospholipid double layers, have been extensively studied over the years as a means of drug administration. Conventional manufacturing techniques like thin-film hydration and extrusion have limitations in controlling liposome size and distribution. Microfluidics enables superior tuning of parameters during the self-assembly of liposomes, producing uniform populations. This review summarizes microfluidic methods for engineering liposomes, including hydrodynamic flow focusing, jetting, micro mixing, and double emulsions. The precise control over size and lamellarity afforded by microfluidics has advantages for cancer therapy. Liposomes created through microfluidics and designed to encapsulate chemotherapy drugs have exhibited several advantageous properties in cancer treatment. They showcase enhanced permeability and retention effects, allowing them to accumulate specifically in tumor tissues passively. This passive targeting of tumors results in improved drug delivery and efficacy while reducing systemic toxicity. Promising results have been observed in pancreatic, lung, breast, and ovarian cancer models, making them a potential breakthrough in cancer therapy. Surface-modified liposomes, like antibodies or carbohydrates, also achieve active targeting. Overall, microfluidic fabrication improves reproducibility and scalability compared to traditional methods while maintaining drug loading and biological efficacy. Microfluidics-engineered liposomal formulations hold significant potential to overcome challenges in nanomedicine-based cancer treatment.

Fmoc-FF hydrogels and nanogels for improved and selective delivery of dexamethasone in leukemic cells and diagnostic applications

Dexamethasone (DEX) is a synthetic analogue of cortisol commonly used for the treatment of different pathological conditions, comprising cancer, ocular disorders, and COVID-19 infection. Its clinical use is hampered by the low solubility and severe side effects due to its systemic administration. The capability of peptide-based nanosystems, like hydrogels (HGs) and nanogels (NGs), to serve as vehicles for the passive targeting of active pharmaceutical ingredients and the selective internalization into leukemic cells has here been demonstrated. Peptide based HGs loaded with DEX were formulated via the “solvent-switch” method, using Fmoc-FF homopeptide as building block. Due to the tight interaction of the drug with the peptidic matrix, a significant stiffening of the gel (G′ = 67.9 kPa) was observed. The corresponding injectable NGs, obtained from the sub-micronization of the HG, in the presence of two stabilizing agents (SPAN®60 and TWEEN®60, 48/52 w/w), were found to be stable up to 90 days, with a mean diameter of 105 nm. NGs do not exhibit hemolytic effects on human serum, moreover they are selectively internalized by RS4;11 leukemic cells over healthy PBMCs, paving the way for the generation of new diagnostic strategies targeting onco-hematological diseases.

Anti-Netrin-1 decorated nanoparticles combined with chemotherapy for the treatment of triple-negative breast cancer

Nanoparticle's success as drug delivery systems for cancer treatment has been achieved through passive targeting mechanisms. However, tumor heterogeneity and rapid drug clearance limit the treatment efficacy. Improved outcomes and selective drug release can be achieved by grafting ligands at the surface of nanocarriers that bind molecules overexpressed in the tumor microenvironment (TME). In this work, we developed a docetaxel-loaded nanoemulsions (NEs) binding an anti-netrin-1 monoclonal antibody (NP137) to selectively target the netrin-1 protein overexpressed in many different tumors. The goal is to refine a combined approach utilizing NP137 and docetaxel as an improved tumor-targeting chemotherapeutic agent for addressing triple-negative breast cancer (TNBC). Several factors have been considered for the optimization of the active targeted drug delivery system via the click-chemistry conjugation, as the impact of PEGylated surfactant that stabilize the NEs shell on conjugation efficiency, cytocompatibility with EMT6 cell line and colloidal stability over time of NEs. Results showed that a 660Da PEG chain length contributed to NEs colloidal stability and had no impact on cell viability or on the antibody binding ability for its ligand after surface conjugation. Moreover, docetaxel was encapsulated into the oily core of NEs, with an encapsulation efficiency of 70%. To validate our treatment strategy in vivo, the 4T1 murine breast cancer model was used. As a result, the comparison of active-targeted and non-targeted NEs revealed that only active-targeted NE could decrease the tumor growth rate.

Maximum correntropy-based pseudolinear Kalman filter for passive bearings-only target tracking

Maximum correntropy-based pseudolinear Kalman filter for passive bearings-only target tracking

Bacteria-driven nanosonosensitizer delivery system for enhanced breast cancer treatment through sonodynamic therapy-induced immunogenic cell death

BackgroundSonodynamic therapy (SDT) has shown promise as a non-invasive cancer treatment due to its local effects and excellent tissue penetration. However, the limited accumulation of sonosensitizers at the tumor site hinders its therapeutic efficacy. Although nanosonosensitizers have improved local tumor accumulation through passive targeting via the enhanced permeability and retention effect (EPR), achieving sufficient accumulation and penetration into tumors remains challenging due to tumor heterogeneity and inaccurate targeting. Bacteria have become a promising biological carrier due to their unique characteristic of active targeting and deeper penetration into the tumor.MethodsIn this study, we developed nanosonosensitizers consisting of sonosensitizer, hematoporphyrin monomethyl ether (HMME), and perfluoro-n-pentane (PFP) loaded poly (lactic-co-glycolic) acid (PLGA) nanodroplets (HPNDs). These HPNDs were covalently conjugated onto the surface of Escherichia coli Nissle 1917 (EcN) using carbodiimine chemistry. EcN acted as an active targeting micromotor for efficient transportation of the nanosonosensitizers to the tumor site in triple-negative breast cancer (TNBC) treatment. Under ultrasound cavitation, the HPNDs were disrupted, releasing HMME and facilitating its uptakes by cancer cells. This process induced reactive oxygen species (ROS)-mediated cell apoptosis and immunogenic cell death (ICD) in vitro and in vivo.ResultsOur bacteria-driven nanosonosensitizer delivery system (HPNDs@EcN) achieved superior tumor localization of HMME in vivo compared to the group treated with only nanosonosensitizers. This enhanced local accumulation further improved the therapeutic effect of SDT induced-ICD therapeutic effect and inhibited tumor metastasis under ultrasound stimulation.ConclusionsOur research demonstrates the potential of this ultrasound-responsive bacteria-driven nanosonosensitizer delivery system for SDT in TNBC. The combination of targeted delivery using bacteria and nanosonosensitizer-based therapy holds promise for achieving improved treatment outcomes by enhancing local tumor accumulation and stimulating ICD.Graphical

A novel NIR-II FL/ PA imaging-guided synergistic photothermal-immune therapy: Biomineralizing nanosystems integrated with anti-tumor and bone repair

Advanced stages of breast cancer are frequently complicated by bone metastases, which cause significant cancer-related bone destruction and mortality. However, the early precise theranostics of bone metastasis remains a formidable challenge in clinical practice. Herein,a novel all-in-one nanotheranostic system (ABI NYs) combining NIR-II FL/PA dual-modal imaging with photothermal-immunity therapeutic functionalities in one component was designed to precisely localize bone metastasis microscopic lesions and achieve complete tumor ablation at an early stage. The surface modification of the nanosystem with ibandronate (IBN) facilitates both passive and active targeting, significantly improving the detection rate of bone metastasis and suppressing the bone resorption. Superior photothermal performance produces sufficient heat to kill tumor cells while stimulating the upregulation of heat shock proteins 70 (HSP70), which triggers the immunogenic cell death (ICD) effect and the anti-tumor immune response. These all-in-one nanosystems precisely demonstrated early lesion localization in bone metastases and total tumor ablation with a single integration via "one-component, multi-functions" technique. To sum up, ABI NYs, as novel biomineralizing nanosystems integrated with anti-tumor and bone repair, present a synergistic therapy strategy, providing insight into the theranostics of bone metastases and clinical research.

Surface acoustic wave reflective delay line as passive cooperative target for wireless sub-surface sensing in liquid using ground penetrating radar

Surface acoustic wave reflective delay line as passive cooperative target for wireless sub-surface sensing in liquid using ground penetrating radar

Platform Design of Passive Target Perception and Localization Based on Sensor Networks

With the rapid development, extensive knowledge, and diverse application scenarios of target perception and positioning technology in sensor networks, a passive target perception and localization platform based on Wireless Sensor Networks (WSN) has been designed. The platform is mainly applied for the teaching of electronic information, communication, and Internet of Things (IoT) engineering. The platform follows the teaching concept of “developing students’ ability to solve complex engineering problems” in the emerging engineering discipline and combines experimental simulation with real-world testing, as well as integrating scientific research and teaching. It encompasses technical elements such as perception and localization theory, sparse representation classification modeling, solving underdetermined equations, data analysis, and sparse coding, as well as nontechnical aspects such as team collaboration and cost budgeting. The platform boasts high fidelity and scalability, providing students with the opportunity to develop comprehensive practical and innovative skills in solving complex engineering problems.

Regulating Drug Release with Microspheres: Formulation, Mechanisms, and Challenges

Controlled drug release is a critical component of current drug delivery systems, aiming to improve therapeutic efficacy while minimizing negative effects. Because of their tunable features and numerous applications, microspheres have emerged as adaptable carriers for achieving controlled medication release. This review paper delves into the formulation techniques, mechanisms, and issues connected with controlling drug release utilizing microspheres. The essay begins by discussing the importance of controlled medication release in healthcare and the critical role that microspheres play in accomplishing this goal. It then looks into the numerous formulation options for microspheres, including material selection, production processes, and drug inclusion techniques. The impact of microsphere properties such as particle size, shape, and drug loading on release kinetics is also thoroughly examined. The processes influencing drug release from microspheres are described in detail, including diffusion-controlled, erosion-controlled, and swelling-controlled release mechanisms and the interaction of polymer characteristics and drug-polymer interactions. The article looks at sophisticated methods for producing targeted drug release, including exterior stimuli-responsive microspheres and internal stimuli-responsive systems. Site-specific targeting strategies are investigated, including passive targeting via the increased permeability and retention (EPR) effect and active targeting via ligand-functionalized microspheres. Despite its promise, microsphere-based drug delivery systems face a number of obstacles. Major challenges are burst release, stability, scale-up, immunogenicity, and regulatory issues. In the context of microsphere-based drug delivery, recent advances in enhanced characterization techniques, nanotechnology integration, combination therapies, personalized medicine, and new trends are discussed.

Potent cancer therapy by liposome microstructure tailoring with active-to-passive targeting and shell-to-core thermosensitive features

Liposomes have been widely studied as drug carriers for clinical application, and the key issue is how to achieve effective delivery through targeting strategies. Even though certain cell-level targeting or EPR effect designs have been developed, reaching sufficient drug concentration in intracellular regions remains a challenge due to the singularity of functionality. Herein, benefiting from the unique features of tumor from tissue to cell, a dual-thermosensitive and dual-targeting liposome (DTSL) was creatively fabricated through fine microstructure tailoring, which holds intelligent both tissue-regulated active-to-passive binding and membrane-derived homologous-fusion (HF) properties. At the micro level, DTSL can actively capture tumor cells and accompany the enhanced HF effect stimulated by self-constriction, which achieves a synergistic promotion effect targeting tissues to cells. As a result, this first active-then passive targeting process makes drug delivery more accurate and effective, and after dynamic targeting into cells, the nucleus of DTSL undergoes further thermally responsive contraction, fully releasing internal drugs. In vivo experiments showed that liposomes with dual targeting and dual thermosensitive features almost completely inhibited tumor growth. Summarized, these results provide a reference for a rational design and microstructural tailoring of the liposomal co-delivery system of drugs, suggesting that active-to-passive dual-targeting DTSL can function as a new strategy for cancer treatment.

Active targeting tumor therapy using host-guest drug delivery system based on biotin functionalized azocalix[4]arene

Host-guest drug delivery systems (HGDDSs) provided a facile method for incorporating biomedical functions, including efficient drug-loading, passive targeting, and controlled drug release. However, developing HGDDSs with active targeting is hindered by the difficult functionalization of popular macrocycles. Herein, we report an active targeting HGDDS based on biotin-modified sulfonated azocalix[4]arene (Biotin-SAC4A) to efficiently deliver drug into cancer cells for improving anti-tumor effect. Biotin-SAC4A was synthesized by amide condensation and azo coupling. Biotin-SAC4A demonstrated hypoxia responsive targeting and active targeting through azo and biotin groups, respectively. DOX@Biotin-SAC4A, which was prepared by loading doxorubicin (DOX) in Biotin-SAC4A, was evaluated for tumor targeting and therapy in vitro and in vivo. DOX@Biotin-SAC4A formulation effectively killed cancer cells in vitro and more efficiently delivered DOX to the lesion than the similar formulation without active targeting. Therefore, DOX@Biotin-SAC4A significantly improved the in vivo anti-tumor effect of free DOX. The facilely prepared Biotin-SAC4A offers strong DOX complexation, active targeting, and hypoxia-triggered release, providing a favorable host for effective breast cancer chemotherapy in HGDDSs. Moreover, Biotin-SAC4A also has potential to deliver agents for other therapeutic modalities and diseases.

A quantitative MRI-based approach to estimate the permeation and retention of nanomedicines in tumors

Despite the potential of the enhanced permeability and retention (EPR) effect in tumor passive targeting, many nanotherapeutics have failed to produce meaningful clinical outcomes due to the variable and challenging nature of the tumor microenvironment (TME) and EPR effect. This EPR variability across tumors and inconsistent translation of nanomedicines from preclinical to clinical settings necessitates a reliable method to assess its presence in individual tumors. This study aimed to develop a reliable and non-invasive approach to estimate the EPR effect in tumors using a clinically compatible quantitative magnetic resonance imaging (qMRI) technique combined with a nano-sized MRI contrast agent. A quantitative MR imaging was developed using a dynamic contrast-enhanced (DCE) MRI protocol. Then, the permeability and retention of the nano-sized MRI contrast agent were evaluated in three different ovarian xenograft tumor models. Results showed significant differences in EPR effects among the tumor models, with tumor growth influencing the calculated parameters of permeability (Ktrans) and retention (Ve) based on Tofts pharmacokinetic (PK) modeling. Our data indicate that the developed quantitative DCE-MRI method, combined with the Tofts PK modeling, provides a robust and non-invasive approach to screen tumors for their responsiveness to nanotherapeutics. These results imply that the developed qMRI method can be beneficial for personalized cancer treatments by ensuring that nanotherapeutics are administered only to patients with tumors showing sufficient EPR levels.

Asiatic acid cyclodextrin inclusion micro-cocrystal for insoluble drug delivery and acute lung injury therapy enhancement

BackgroundAcute lung injury (ALI) is a fatal respiratory disease caused by overreactive immune reactions (e.g., SARS-CoV-2 infection), with a high mortality rate. Its treatment is often compromised by inefficient drug delivery barriers and insufficient potency of the currently used drugs. Therefore, developing a highly effective lung-targeted drug delivery strategy is a pressing clinical need.ResultsIn this study, the micro-sized inclusion cocrystal of asiatic acid/γ-cyclodextrin (AA/γCD, with a stoichiometry molar ratio of 2:3 and a mean size of 1.8 μm) was prepared for ALI treatment. The dissolution behavior of the AA/γCD inclusion cocrystals followed a “spring-and-hover” model, which meaned that AA/γCD could dissolve from the cocrystal in an inclusion complex form, thereby promoting a significantly improved water solubility (nine times higher than free AA). This made the cyclodextrin-based inclusion cocrystals an effective solid form for enhanced drug absorption and delivery efficiency. The biodistribution experiments demonstrated AA/γCD accumulated predominantly in the lung (Cmax = 50 µg/g) after systemic administration due to the micron size-mediated passive targeting effect. The AA/γCD group showed an enhanced anti-inflammatory therapeutic effect, as evidenced by reduced levels of pro-inflammatory cytokines in the lung and bronchoalveolar lavage fluids (BALF). Histological examination confirmed that AA/γCD effectively inhibited inflammation reactions.ConclusionThe micro-sized inclusion cocrystals AA/γCD were successfully delivered into the lungs by pulmonary administration and had a significant therapeutic effect on ALI.Graphic abstract

Targeting Strategies for Site-Specific mRNA Delivery.

mRNA therapeutics hold great promise for disease treatment, yet a key challenge lies in achieving site-specific mRNA delivery to maximize therapeutic efficacy while minimizing off-target side effects. This viewpoint delves into multiple complementary targeting strategies to achieve precise site-specific mRNA delivery, covering topics of administration routes, passive targeting, and active targeting. It highlights the critical importance of rationally designed nanocarriers for obtaining desired therapeutic effects and accelerating the clinical translation of mRNA therapeutics.