Nanocarriers For Delivery Research Articles

Membrane Budding Inspired Biomimetic Nanocarrier Delivers Brain‐derived Neurotrophic Factor to Improve AD Cognition

AbstractNeurotropic factors, crucial for neural cell maturation and proliferation, hold great therapeutic potential for treating neurodegenerative diseases but face challenges in brain delivery. This study introduces a novel membrane budding‐inspired lipoprotein biomimetic nanocarrier for efficient packaging and precise brain delivery of brain‐derived neurotrophic factor (BDNF). The nanocarrier is created by mixing protein‐loaded biomimetic gel with liposomes composed of lipids prone to forming liquid‐disordered and liquid‐ordered phases. This interaction triggers phase separation and lipid membrane rearrangement, enabling effective protein encapsulation. To enhance blood‐brain barrier permeability and target damaged cerebral vasculature in Alzheimer's Disease, the nanocarrier (RAP‐BHP‐rHDL) is functionalized with Apolipoprotein E3 and αRAP peptides. The obtained RAP‐BHP‐rHDL alleviates neuronal damage, promotes neurogenesis, normalizes the cerebral microvasculature, improves the function of neurovascular units, and restores memory function in 5 × FAD mice. This innovative packaging approach and biomimetic nanocarrier design offer a promising strategy for delivering neurotropic factors to the central nervous system, potentially advancing the management of neurodegenerative diseases.

In vitro evaluation of lipidic nanocarriers for mebendazole delivery to improve anticancer activity

Objective Enhance the anticancer activity of the repurposed drug Mebendazole (MBZ) against A549 cell lines by developing nanostructured lipid carriers (NLCs). Significance MBZ, an anthelmintic drug, exhibits anticancer properties primarily through the inhibition of Ran GTPase and mitotic spindle assembly. Enhancing its delivery and efficacy via NLC could provide a novel and effective approach for lung cancer treatment. Methods NLCs were prepared by mixing different ratios of solid lipid (Stearic acid) and liquid lipid (Oleic acid) with surfactants and emulsifiers. The NLCs were fully characterized to ensure stability, particle size, zeta potential, and encapsulation efficiency (EE%). The stability of the NLCs was monitored over a 3-week period. The anticancer activity of MBZ-NLCs was evaluated using IC50 assays and in vitro scratch assays. Results The NLCs exhibited an average particle size of 300 ± 10 nm and a zeta potential of -27 ± 0.5 mV, indicating good stability. EE% significantly improved from 40% in conventional liposome formulations to 90.7% in NLCs. The anticancer activity of MBZ-NLCs was markedly enhanced, with an IC50 of 62 nM compared to 581 nM for free MBZ, representing a 10-fold increase in potency. Additionally, in vitro scratch assays revealed that MBZ-NLCs effectively prevented cell-cell contact, further supporting their potential for improved therapeutic efficacy. Conclusions MBZ-NLCs exhibit significantly improved stability, encapsulation efficiency, and anticancer activity compared to free MBZ. These promising results suggest that MBZ-NLCs could be a potent therapeutic approach for lung cancer treatment, warranting further in vivo studies and exploration of different administration routes.

Dynamic reorganization of multivesicular bodies and exosome production impacted by sonoporation

Naturally occurring cell-derived extracellular vesicles (EVs) have emerged as attractive nanocarriers for drug delivery. However, production of large quantities of EVs for clinical applications in a scalable manner remains a significant challenge. This study investigated at the single cell level how sonoporation, or membrane poration produced by ultrasound-induced microbubble cavitation, impacts EV production using mouse macrophage RAW 264.7 cells stably expressing CD63-GFP as a model system. Real-time fluorescence videomicroscopy detected rapid changes in CD63-GFP, a tetraspanin family member highly enriched in intraluminal vesicles tagged with GFP, to track changes in multivesicular bodies (MVBs), which are the cellular compartments where exosomes originate within the cells. Our results revealed distinct dynamic changes in CD63-GFP intensity and distribution in RAW 264.7 cells in terms of response time and duration depending on whether the cells were directly or indirectly impacted by sonoporation, suggesting reorganization of MVBs in response to direct and indirect mechanisms resulted from the mechanical impact of ultrasound pulse on the cells. Analysis of the supernatant from sonoporation-treated RAW 264.7 cells expressing CD63-GFP demonstrated a delayed and sustained increase in the production of CD63-GFP-positive EVs. These results show the robust and detailed effect of sonoporation and reveal insights into sonoporation-induced EV release useful for guiding the application of sonoporation to enhance large-scale EV production.

Co-loading Radio-photosensitizer Agents on Polymer and Lipid-based Nanocarriers for Radio-photodynamic Therapy Purposes: Review.

Polymer and lipid-based nanocarriers are a state-of-art in nanomedicine and in co-drug delivery of drugs that could merges various diagnostic and treatment modalities such radiotherapy (RT), photodynamic therapy (PDT) and chemotherapy (CT) in cancer therapy. Among various shapes and nanostructures, polymer and lipid-based nanocarriers have the potential to carry two drugs in same time to cells. However, hydrophobic and hydrophilic drug can be loaded in between layers as well as in the core of these nanocarriers, simultaneously. This advantage of NPs can be employed in combination therapy. Radiosensitizer and photosensitizer agents play a critical role in radio-photodynamic therapy (RT-PDT) of cancer. Co-delivery of these agents to cancerous cells is advantageous to cancer therapy but still remain as a challenge of RT-PDT. However, in this review, we have highlighted the challenges of RT-PDT and role of polymer and lipid-based nanocarriers to codelivery of hydrophobic and hydrophilic agents as radio-photosensitizers. Hence, the different kinds of Poly (lactic-co-glycolic acid) nanoparticles (NPs) have been categorized. Then, the biophysical mechanism of radio- photosensitizer agents with co-loading on polymer and lipid-based nanocarriers in RT-PDT treatment of cancer has been outlined. Finally, attention has been drawn to polymer and lipid-based nanocarriers in codrugs delivery. Taken together, this work presents the latest updates on this area and highlighted the pros and cons of co-delivery for RT-PDT purposes.

The Neoteric Paradigm of Biomolecule-Functionalized Albumin-Based Targeted Cancer Therapeutics.

Albumin is a nature-derived, versatile protein carrier, that has been explored extensively by researchers for anticancer drug delivery due to its role in enhancing drug stability, solubility, circulation time, targeting capabilities, and overall therapeutic efficacy. Albumin nanoparticles possess inherent biocompatibility, biodegradability, and passive tumor-targeting ability due to the enhanced permeability and retention effect. However, non-specific accumulation of cytotoxic agents in healthy tissues remains a challenge. In this paper, the functionalization of albumin nanoparticles using various biomolecules including antibodies, nucleic acids, proteins and peptides, vitamins, chondroitin sulfate, hyaluronic acid, and lactobionic acid have been discussed which enables specific recognition and binding to cancer cells. Furthermore, we highlight the supremacy of such a targeted approach in tumor-specific drug delivery, minimization of off-target effects, potential improvement in therapeutic efficacy, cellular internalization, reduced side effects, and better clinical outcomes. This review centers on how they have revolutionized the field of biomedical research and tuned into an excellent targeted approach. In conclusion, this review highlights in detail the role of albumin as a nanocarrier for tumor-targeted delivery using biomolecules as ligands.

Priming immunity via herbal components and their nanomedicines for the treatment of cancer

Recently, immunotherapy has redefined cancer treatment by promoting the rapid killing of tumor cells through the immune system. Herbal medicines have been increasingly used as adjunct therapies to complement cancer treatment along with chemotherapy and radiotherapy to delay tumor development, reduce pain, and prolong patient survival. However, the potential immunotherapeutic effects of these herbal derivatives are limited by their structural instability, poor membrane permeability, and low bioavailability. To address this issue, nanotechnology has been used to enhance the activity of active compounds. Therefore, this review focuses on the effectiveness of the active ingredients of herbal medicines in suppressing tumor progression by modulating both the innate and adaptive immune systems, challenges in their delivery, and the application of nanocarriers for the effective delivery of these herbal components.

Camel milk-derived exosomes as novel nanocarriers for curcumin delivery in lung cancer

Cancer remains a leading cause of mortality, with non-small cell lung cancer (NSCLC) being a primary contributor to cancer-related deaths. Traditional treatment strategies such as chemotherapy, radiation, and hormone therapy often present challenges, including severe side effects, drug resistance, and toxicity. Recent advancements in nanotechnology aim to enhance the effectiveness of cancer therapies by targeting drugs selectively and specifically to tumor cells. Among these innovations, exosomes, or small extracellular vesicles (EVs), have emerged as promising carriers for drug delivery due to their natural origin and ability to encapsulate both small molecules and biologics. This study explores the use of exosomes derived from camel milk in Hail, Saudi Arabia, as a vehicle for delivering curcumin (CUR), a polyphenol with known chemopreventive properties but limited bioavailability. Camel milk was processed to isolate exosomes through differential centrifugation, followed by characterization using dynamic light scattering, zeta potential measurements, and Western blot analysis to confirm exosomal markers. The encapsulation of CUR into camel milk-derived exosomes demonstrated a 20% loading efficiency as analyzed by UPLC. In vitro antiproliferative assays revealed that the exosomal formulation of CUR (ExoCUR) significantly enhanced cytotoxicity against drug -sensitive (A549) and taxol-resistant (A549TR) lung cancer cells compared to free CUR. Molecular docking studies and molecular dynamics simulations indicated that CUR has a strong binding affinity for the epidermal growth factor receptor (EGFR), comparable to the established drug gefitinib. Furthermore, CUR effectively downregulated EGFR and STAT3 expression in cancer cells, suggesting its potential to disrupt key signaling pathways involved in tumor progression. Our findings highlight the potential of camel milk-derived exosomes as an effective and biocompatible delivery system for CUR, offering a promising strategy to overcome the limitations of current cancer therapies and enhance the therapeutic efficacy of chemopreventive agents.

Poloxamer®s anchored with TAT enhance blood–brain barrier penetration of carbamazepine for the treatment of epilepsy: an in vivo study

Carbamazepine is a pharmacological medication commonly prescribed to treat epilepsy. Dose adjustments, poor bioavailability, and prolonged side effects present significant challenges associated with its use. Poloxamer micelles have demonstrated exceptional properties as nanocarriers for drug delivery. This research aimed to develop Poloxamer nanomicelles containing carbamazepine and assess their potential to cross the blood–brain barrier.Poloxamer 407 and P-85 micelles, anchored with TAT as a ligand and containing carbamazepine, were prepared. The morphology, entrapment efficiency, drug release, stability, and toxicity of nanomicelles were examined, along with animal studies conducted to evaluate their anticonvulsant effects. The distribution of carbamazepine-Poloxamer in the brain and plasma was assessed.The results indicated the successful formation of spherical nanomicelles with an average size of less than 100 nm, and carbamazepine was effectively incorporated into the micelles. Formulations composed of mixtures of Poloxamer exhibited a high encapsulation efficiency of approximately 92.1% and remained stable for three months. A sustained release of carbamazepine was observed for up to 72 h. The anticonvulsant effect of carbamazepine-loaded nanomicelles in mice was found to be significantly greater than that of those treated with carbamazepine solution, with the effect increasing by approximately tenfold. Compared to free carbamazepine, the carbamazepine-loaded nanomicelles exhibited a 5.5-fold increase in the brain targeting index, with no toxicity observed in mice treated with these nanomicelles. These findings suggest that Poloxamer micelles represent a promising nanoscale, controlled-release delivery system that is free from toxicity and can enhance the penetration of carbamazepine into the brain while improving its anticonvulsant activity.Graphical

Engineered Porous Beta-Cyclodextrin-Loaded Raloxifene Framework with Potential Anticancer Activity: Physicochemical Characterization, Drug Release, and Cytotoxicity Studies.

Cancer ranks as the second most common cause of mortality as depicted by the World Health Organization, with one in six deaths being cancer-related mortality. Taking the lead in females, breast cancer is the most common neoplasm. Raloxifene, a selective estrogen receptor modulator, has been utilized as a chemotherapeutic agent for the treatment of breast cancer in postmenopausal women. However, its poor aqueous solubility hinders its clinical applications. Beta-cyclodextrin-based framework is a novel class of nano-vectors that used to potentiate the solubility and dissolution rate of poorly soluble drugs. The present study investigates the solubility and dissolution rate enhancement as well as the potential cytotoxic activity of raloxifene-loaded nanosponges formulation. The fabrication and optimization of cyclodextrin nanosponges crosslinked with diphenyl carbonate was portrayed through stoichiometric selection of cyclodextrin-to-crosslinker ratio. The complexation phenomenon and nanosponges formation were validated using FTIR, PXRD, TEM, and SEM examination. Raloxifene-loaded nanosponges exhibited a 440±8.5 nm particle size, a negative zeta potential of 25.18±2.3 mV and a partial drug incorporation. Moreover, the drug loaded nanosponges demonstrated an in-vitro significantly enhanced dissolution behavior. Furthermore, the in-vitro cytotoxicity of the raloxifene-loaded nanosponges on MCF-7 breast cancer cell lines was statistically significant compared to the complex-free raloxifene. The cytotoxic behavior provided evidence that the incorporation of raloxifene within the nanosponges structure enhanced its anticancer activity and represents a potential nanocarrier for anticancer agent delivery.

MIL-101 magnetic nanocarrier for solid-phase delivery of doxorubicin to breast and lung cancer cells

MIL-101 magnetic nanocarrier for solid-phase delivery of doxorubicin to breast and lung cancer cells

Polymersomes as Next Generation Nanocarriers for Drug Delivery: Recent Advances, Patents, Synthesis and Characterization

Background: Polymersomes (PS), self-assembled nanostructures formed by amphiphilic block copolymers, have garnered significant attention in recent years due to their unique properties and versatile applications in the fields of drug delivery and biomedicine. They are being prepared for a wide range of complex medicinal compounds, including nucleic acids, proteins, and enzymes. Polymersomes have lately been used as vehicles for delivering varied therapeutic substances and regulating ROS (reactive oxygen species). Due to their immunogenic features, polymersomes could play a critical role in enhancing subunit vaccine and drug delivery against COVID-19 infection. Objective: The prime purpose of this manuscript is to furnish an extensive overview of polymersomes, highlighting their recent advances, fabrication methods, characterization techniques, and pharmaceutical applications. Methods: The article has been amassed using several online and offline manuscripts from reputed journals, books, and other resources. Besides this, various user-friendly interfaces, like Pubmed, Google Scholar, etc, have been utilized to gather the latest data about polymersomes. This domain encompasses recent advancements in the realm of innovations about the delivery of drugs through polymeric vesicles. This field involves innovations or developments in nanocarrier systems as they are efficaciously employed to deliver the desired moiety to the targeted site. Results: PS have been discovered to exhibit remarkable promise in addressing various challenges associated with inadequate bioavailability, targeted drug delivery, dosing frequency, and diminished toxic effects. Over the past decade, such nanovesicles have been effectively employed as a complementary approach to address the issues arising from poorly soluble medications. However, this domain still requires further focus on novel breakthroughs. Conclusion: Polymersomes demonstrate unparalleled potential as innovative carriers, exhibiting remarkable versatility and exceptional biocompatibility. This concise review underscores their extraordinary prospects in diverse fields, accentuating their distinctive attributes and opening new avenues for groundbreaking applications.

PEGylated lipid polymeric nanoparticles for management of rheumatoid arthritis

PEGylation, an extensively used surface modification method for nanoparticles (NPs), continues to hold promise for optimizing therapy for various medical conditions by achieving efficient and selective delivery of multiple therapeutics and nanocarriers. Rheumatoid arthritis is a chronic autoimmune and inflammatory disease treated mainly by disease-modifying antirheumatic drugs (DMARDs) (e.g., leflunomide); however, these drugs suffer from systemic exposure and adverse effects. Leflunomide (LEF) was loaded into PEGylated (PEG)-lecithin chitosan nanoparticles (LCNPs) to enhance its therapeutic efficacy and safety profile. LEF-PEG-LCNPs showed a particle size of 115.31 ±3.24 nm, a zeta potential of 31.3±1.8 mV, an entrapment efficiency of 89.63 ±2.25 %, and an improved release profile than non-pegylated LCNPs and LEF-pure. Fourier transform-infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and transmission electron microscopy (TEM) were also performed. The effects of orally administrated LEF-pure, LEF-marketed, LEF-LCNPs and LEF-PEG-LCNPs against Complete Freund’s Adjuvant (CFA)-induced rheumatoid arthritis (RA) in rats were investigated. LEF-PEG-LCNPs showed more significant inhibition of paw edema (72.74%), rheumatoid factor RF (40.76%), TNF-α (55.6%), IL-6 (47.42%), ALT (80.59%), and AST (39.83%) as compared to positive control. Furthermore, histopathological studies showed a nearly normal appearance of bone trabecular tissue, liver, kidney, lung, and heart. This highlights LEF-PEG-LCNPs as an exceptional anti-rheumatoid arthritis therapy compared to pure and marketed formulations.

Bi-modal confirmation of liposome delivery to the brain after focused ultrasound-induced blood-brain barrier opening

Focused ultrasound-mediated opening of the blood-brain barrier offers a great opportunity to deliver therapeutics into hard-to-treat brain tumors such as glioblastoma multiforme or diffuse midline glioma. However, the potential of the technique to offer a time window for efficient nanomedicine delivery has not been thoroughly studied. Non-invasive and targeted delivery of large drug-loaded nanocarriers, such as liposomes, could offer a safe and scalable method of personalized therapy for the treatment of brain pathologies. Additionally, it is essential to monitor the safety and efficacy of such treatments, tracking drug delivery in real-time through quantitative medical imaging.In this study, liposomes were modified to have an MRI contrast agent (i.e., Gd) in both lipid membrane and core, while an infrared dye (i.e., CW800) was coupled to lipids introduced in the lipid bilayer for bimodal detection and treatment verification. Targeted delivery of 110nm-in-diameter liposomes to the brain was quantified using 9.4-T MRI and near infrared fluorescence imaging. The spatiotemporal distribution of liposomes in vivo was assessed up to 4 hours post treatment using T1 weighted MRI. In vivo MRI signal co-localized with NIRF signal from excised brains ex vivo. Passive acoustic detection during treatments revealed a correlation between acoustic signal and MRI contrast, providing a scalable metric for assessing clinical treatment efficacy in real-time. In conclusion, therapeutic ultrasound exposure can enhance delivery of large trackable nanoparticles into the brain, while enabling real-time treatment monitoring and verification.

Nanocarrier Delivery of Cisplatin and its Patent Studies

Cisplatin, also known as cis-(diammine) dichloridoplatinum (II) or CDDP, is frequently used as first-line chemotherapy in head, neck, and lung malignancies. It can be given as a single agent or in conjunction with radiation therapy and/or other anti-cancer chemotherapeutic agents. Now, experiences based on PEGylated liposome-based nano-formulations AroplatinTM, LipoplatinTM, and SPI-077 are undergoing clinical trials. These cisplatin drug delivery systems resolve issues like poor solubility in water, drug resistance, and toxicity by using nanocarrier systems. The above-cited nano-delivery technologies for cisplatin have been extensively described in numerous pieces of literature existing in various databases. Essentially, this evaluation gives a severe focus on newer information, invented news, and up-to-date articles regarding various carrier systems for CDDP and the newer patents of this drug formulation.

Safety of Zein Nanoparticles on Human Innate Immunity and Inflammation.

In recent years, natural polymers have attracted great interest for the development of release systems for vaccine formulations and drug delivery. Zein, a hydrophobic proline-rich protein mixture obtained from maize, is one of the most widely used polymers, very promising for applications in tissue engineering and the parenteral delivery of bioactive agents. Still, we have a limited understanding of the interaction between zein particles and the human immune system, in particular innate immunity/inflammation, which is the first line of defense of our body. Assessing the immune safety of nanoparticles is of central importance for ensuring that nano-formulations for medical use do not cause adverse effects on human health. Here, we evaluated the capacity of zein nanoparticles to induce/modulate the innate/inflammatory response, the development of innate memory, and the macrophage polarization by using reliable in vitro systems based on human primary monocytes and monocyte-derived macrophages. We observed that zein nanoparticles do not influence any of these aspects of the innate immune/inflammatory response, suggesting its safety and its potential efficiency as a nanocarrier for drug or antigen delivery.

Development of Stable and Intensified Mixing Processes for the Precise and Scalable Production of Uniform Drug Delivery Nanocarriers.

Nanocarriers show great promise in drug delivery but face challenges in stability, uniformity, and morphology control. This work introduces an enhanced mixing process to overcome these obstacles, specifically aiming to produce consistently sized poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with anti-tumor drugs. By innovatively integrating a pulsation dampener into the microfluidic channels of a continuous flow preparation system, the flow stability of piston pumps is improved nearly tenfold. Consequently, large-scale production of uniformly sized nanoparticles with customizable dimensions is achieved through nanoprecipitation. Furthermore, incorporating terminal double-bond-functionalized poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-maleimide (PLGA-PEG-Mal) enables these nanoparticles to act as nano-crosslinkers. This facilitates in situ crosslinking with thiolated hyaluronic acid via a spontaneous thiol-ene coupling reaction under physiological conditions, allowing for minimally invasive drug administration and significantly enhancing localized drug retention. The material's degradability in the presence of endogenous enzymes ensures controlled drug release, as demonstrated with the anti-tumor drug doxorubicin (DOX). Validation in a murine breast cancer model shows reduced toxicity and a substantial reduction in tumor weight compared to the free DOX group. These findings confirm the approach's effectiveness for breast cancer treatment and pave the way for innovative solutions in nanomedicine, providing a practical microfluidic mixing system for the design and large-scale production of nanomedicines.

Geldanamycins: Potent Hsp90 Inhibitors with Significant Potential in Cancer Therapy.

Geldanamycin, an ansa-macrolide composed of a rigid benzoquinone ring and an aliphatic ansa-bridge, was isolated from Streptomyces hygroscopicus. Geldanamycin is a potent heat shock protein inhibitor with remarkable antiproliferative activity. However, it shows pronounced hepatotoxicity in animal models and unfavorable pharmacokinetic properties. Four geldanamycin analogs have progressed through various phases of clinical trials, but none have yet completed clinical evaluation or received FDA approval. To enhance the efficacy of these Hsp90 inhibitors, strategies such as prodrug approaches or nanocarrier delivery systems could be employed to minimize systemic and organ toxicity. Furthermore, exploring new drug combinations may help overcome resistance, potentially improving therapeutic outcomes. This review discusses the mechanism of action of geldanamycin, its pharmacokinetic properties, and the various approaches employed to alleviate its toxicity and maximize its clinical efficacy. The main focus is on those derivatives that have progressed to clinical trials or that have shown important in vivo activity in preclinical models.

Plasmomagnetic hybrid gold nanostructures as multifunctional nanocarriers for drug delivery, MRI contrast, and photothermal therapy of drug-resistant cancer cells

Presenting a simple efficient method, plasmomagnetic hybrid nanostructures (PNIPAM coated gold nanorods-dexpion hybrid nanostructure, PN-GDHNs) capable of serving as dual drug nanocarriers, MRI contrast, and photothermal agents for cancer therapy were synthesized. The cisplatin (CDDP) and doxorubicin (DOX) were loaded on PN-GDHNs and tested for their drug release, cytotoxicity, photothermal, and MRI contrast in vitro. We found that the drug release was controlled by pH and temperature, and the cytotoxicity was enhanced by the combination of chemotherapy and photothermal therapy. We also found that the PN-GDHNs could overcome the drug resistance of MCF7 breast cancer cells and improve the MRI contrast. We achieved a high cancer cell-killing efficiency of 97.3 ± 0.4 % in one dose with low drug concentration and laser power. Our results suggest that PN-GDHNs are promising multifunctional nanocarriers for cancer therapy applications.

Development of Chitosan-Coated Graphene Oxide and Iron Oxide Nanocomposites for Targeted Delivery of Camptothecin to Liver Cancer Cells.

Innovative drug delivery platforms for selective, regulated, and sustained release of anticancer drugs are crucial in cancer treatment. This study presents nanoparticles developed from chitosan (CS), graphene oxide (GO), and magnetite (Fe3O4), and their nanocomposites, to enhance the loading and release efficiency of camptothecin (CPT). Nanostructures were characterized using imaging microscopy, FT-IR, and X-ray diffraction, with an average crystallite size of 5.5 nm. Camptothecin binding proportions were 70% for CS, 81% for CS@Fe3O4, 58% for CS@GO, and 74% for CS@GO/Fe3O4. At pH 5.0, CPT release ratios were 87%, 80%, 88%, and 90%, respectively, and at pH 7.4, 84%, 72%, 89%, and 87%. Cytotoxicity was assessed using the MTT assay against HepG2 and SMMC-7721 cancer cells. CPT-CS@GO/Fe3O4 exhibited the highest survival at 5 µM and 12.5 µM concentrations, indicating it as the most effective nanocarrier for camptothecin delivery. The study demonstrates CS@GO/Fe3O4's potential as a superior drug delivery system.

Stable Porous Organic Cage Nanocapsules for pH-Responsive Anticancer Drug Delivery for Precise Tumor Therapy.

The search for drug nanocarriers with stimuli-responsive properties and high payloads for targeted drug delivery and precision medicine is currently a focal point of biomedical research, but this endeavor still encounters various challenges. Herein, a porous organic cage (POC) is applied to paclitaxel (PTX) drug delivery for cancer therapy for the first time. Specifically, water-soluble, stable, and biocompatible POC-based nanocapsules (PTX@POC@RH40) with PTX encapsulation efficiency over 98% can be synthesized by simply grafting nonionic surfactant (Polyoxyl 40 hydrogenated castor oil, RH40) on the POC surface. These PTX@POC@RH40 nanocapsules demonstrate remarkable stability for more than a week without aggregation and exhibit pH-responsive behavior under acidic conditions (pH 5.5) and display sustained release behavior at both pH 7.4 and pH 5.5. Intravenous administration of PTX@POC@RH40 led to a 3.5-fold increase in PTX bioavailability compared with the free PTX group in rats. Moreover, in vivo mouse model experiments involving 4T1 subcutaneous breast cancer tumors revealed that PTX@POC@RH40 exhibited enhanced anticancer efficacy with minimal toxicity compared with free PTX. These findings underscore the potential of POCs as promising nanocarriers for stimuli-responsive drug delivery in therapeutic applications.