Targeted Nano-drug Delivery System Research Articles

Preparation of Glutathione-Regulated Sorafenib Targeted Nanodrug Delivery System and Its Antihepatocellular Carcinoma Activity.

To enhance the therapeutic effect of sorafenib (SOR) on liver cancer, we have developed a targeted nanodrug delivery system with glutathione (GSH) downregulation functionality. The preparation process comprises the synthesis of amino-functionalized mesoporous silica nanoparticles (MSN-NH2), surface modification with ethacrynic acid (EA), loading of SOR into the pores, and final surface coating with hyaluronic acid (HA) to obtain SOR@MSN-EA@HA (SMEH) nanoparticles. SMEH nanoparticles specifically enter tumor cells via CD44 receptor-mediated endocytosis. EA binds to GSH to consume it, while SOR is slowly released from the pores to exert antitumor effects while inhibiting GSH production. This results in sustained oxidative stress in the cells, thus enhancing the antitumor efficacy. Both in vitro and in vivo antitumor experiments as well as hemolysis tests have demonstrated that SMEH nanoparticles can accurately target liver cancer cells, effectively downregulate GSH concentration, exhibit good antitumor effects, and possess excellent safety, showing great potential in tumor treatment.

Co-biopolymer of zein/starch hydrogel incorporated montmorillonite for efficient quercetin delivery in lung cancer treatment

Today, cancer treatment is an important issue in the medical world due to the challenges and side effects of ongoing treatment procedures. Targeted nanodrug delivery systems can replace current methods to mitigate such side effects. In this study, a novel nanocomposite of starch, zein, and MMT with the drug quercetin (QC) was synthesised with the aim of effectively killing A549 cancer cells despite reducing any harmful effects on normal cells, and then the effect of the nanosystem to evaluate the damages on L929 cell lines (healthy) and A549 (cancerous) were investigated. For this purpose, the drug release test from the nanosystem was conducted at two pH levels of 5.4 and 7.4, and it was observed that the nanosystem successfully released 29 % of the QC drug in the first 12 h. The prepared nanocomposites were analysed by XRD, FT-IR, FESEM, DLS, Zeta potential, and MTT techniques. It was found that the nanoparticles exhibited a consistent and even morphology, with an average particle size ranging from 50 to 100 nm. The DLS study provided evidence of the precise range of size and outstanding durability of the nanoparticles. The nanosystem exhibited a notable enhancement in the rate of cell death in malignant tumours, as evidenced by the MTT tests. The synthesised nanosystem showed a precise and pH-dependent release of the drug, which indicates the biocompatibility of the nanocarrier for the QC drug. According to this, it has the capacity to function as an acceptable substitute for the therapeutic techniques that are now being used.

Design and Antimalarial Evaluation of Polydopamine-Modified Methyl Artelinate Nanoparticles.

Targeted nanodrug delivery systems are highly anticipated for the treatment of malaria. It is known that Plasmodium can induce new permeability pathways (NPPs) on the membrane of infected red blood cells (iRBCs) for their nutrient uptake. The NPPs also enable the uptake of nanoparticles (NPs) smaller than 80 nm. Additionally, Plasmodium maintains a stable, slightly acidic, and reductive internal environment with higher glutathione (GSH) levels. Based on this knowledge, methyl artelinate (MA, a prodrug-like derivative of dihydroartemisinin) nanoparticles (MA-PCL-NPs) were developed using poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) by a thin-film dispersion method and were further coated with polydopamine (PDA) to obtain MA-PCL@PDA-NPs with a particle size of ∼30 nm. The biomaterial PDA can be degraded in slightly acidic and reductive environments, thereby serving as triggers for drug release. MA could generate reactive oxygen species and decrease GSH levels, consequently causing parasite damage. The in vitro release experiment results indicated that the cumulative release percentage of MA from MA-PCL@PDA-NPs was considerably higher in phosphate buffer with 10 mM GSH at pH 5.5 (88.10%) than in phosphate buffer without GSH at pH 7.4 (16.98%). The green fluorescence within iRBCs of coumarin 6, the probe of NPs (C6-PCL@PDA-NPs), could be reduced significantly after adding the NPP inhibitor furosemide (p < 0.001), which demonstrated that MA-PCL@PDA-NPs could be ingested into iRBCs through NPPs. In vivo antimalarial pharmacodynamics in Plasmodium berghei K173-bearing mice showed that the inhibition ratio of MA-PCL@PDA-NPs (93.96%) was significantly higher than that of commercial artesunate injection (AS-Inj, 63.33%). The above results showed that the developed MA-PCL@PDA-NPs possessed pH-GSH dual-responsive drug release characteristics and targeting efficacy for iRBCs, leading to higher antimalarial efficacy against Plasmodium.

Rational Design of Targeted Gold Nanoclusters with High Affinity to Integrin αvβ3 for Combination Cancer Therapy.

The unique attributes of targeted nano-drug delivery systems (TNDDSs) over conventional cancer therapies in suppressing off-target effects make them one of the most promising options for cancer treatment. There is evidence that the density of surface-conjugated ligands is a crucial factor in achieving the desired therapeutic efficacy of TNDDSs, but this is hardly manageable in conventional nanomaterials. In this context, ligand-protected gold nanoclusters (AuNCs) are excellent candidates for developing new TNDDSs with a unique control on their surface functionalities, thus helping to achieve enhanced delivery performance. Here, we study the interactions and binding free energies between ten different functionalized Au144(SR)60 (SR = thiolate ligand) nanoclusters and integrin αvβ3 using molecular dynamics simulations and the umbrella sampling method to obtain the optimal formulations. The AuNCs were functionalized with anticancer drugs (5-fluorouracil or signaling pathways inhibitors, such as capivasertib, linifanib, tanespimycin, and taselisib) and integrin-targeting peptides (RGD4C or QS13), and we identified the optimal mixed ligand layer to enhance their binding affinity to the cancer cell receptor. The results showed that changing the proportions of the same type of ligands on the surface of AuNCs led to differences of up to 38 kcal/mol in computed binding free energies. RGD4C as the targeting peptide resulted in greater affinity for αvβ3, and in most formulations studied, a higher amount of drug than peptide was needed. Polar and charged residues, such as Ser123, Asp150, Tyr178, Arg214, and Asp251 were found to play a significant role in AuNC binding. Our simulations also revealed that Mn2+ cations are crucial for stabilizing the αvβ3-AuNC complex. These findings demonstrate the potential of carefully designing the surface composition of TNDDSs to optimize their target affinity and specificity.

CPP10-targeted photoactivatable MOF nanosystem for combined photodynamic Therapy−Chemotherapy of cancer

The annual prevalence of gastric cancer has increased in recent years. Curcumin (CUR) has shown great potential in the treatment of gastric cancer; however, its low bioavailability and poor efficacy hinder its widespread clinical application. Additionally, CUR has been found to be excellent photosensitizer in photodynamic therapy. In this study, the Fe-based metal-organic framework (MOF) Fe Tetrakis (4-carboxyphenyl) porphyrin (Fe-TCPP，FT) was used as a photosensitizer and mononuclear agent. The natural anti-tumor active ingredient CUR was loaded as both a chemotherapeutic agent and photosensitizer to form the nanoparticles CUR@FT (CF). Finally, a cell-penetrating peptide (CPP10) was modified on the surface of the nanoparticles to construct a drug delivery system (named CPP10-PEG@CUR@FT, CCF) that could actively target tumor cells while exerting a synergistic therapeutic effect of chemotherapy and photodynamic therapy. This can improve the efficacy of CUR as a chemotherapeutic drug or photosensitizer, and the high drug load and pH sensitivity of FT nanoparticles provide an excellent carrier for the efficient delivery of CUR. The polyethene glycol (PEG)-conjugated CPP10 (PEG-CPP10) coating allows nanoparticles to specifically target gastric cancer cells, significantly improving the absorption of nanoparticles in vivo and in vitro and improving biosafety. We evaluated the thermal stability, drug loading capacity, and safety of FT as a drug delivery vehicle. We also assessed the in vitro photodynamic performance and toxicity of various nanoparticles and the targeting and biocompatibility of CPP10-PEG@CUR@FT. CPP10-PEG@CUR@FT could specifically target tumor cells, and its effect on killing gastric cancer cells (MKN45) under light was much stronger than that of free CUR. Its toxicity and side effects to other organs and tissues are low, offering good biosafety. The experimental results showed that FT and CUR exerted synergistic effects on photodynamic therapy and chemotherapy. In summary, our novel CUR-loaded targeted nano drug delivery system offers significant advantages by combining photodynamic therapy and chemotherapy for tumor treatment. This approach introduces a new concept for integrating chemotherapy, photodynamic therapy and targeted drug delivery, potentially providing a new strategy for the clinical treatment of gastric cancer.

Methotrexate-loaded manganese nitrogen dual-doped carbon quantum dots as targeted nano drug-delivery system for potential use in cancer theranostics

The present work highlights manganese nitrogen dual-doped carbon quantum dots as a novel pH-sensitive drug delivery system, for the delivery of methotrexate, targeted to cancer cells, along with the simultaneous real-time monitoring of cellular uptake and drug delivery using fluorescence imaging. Briefly, methotrexate was conjugated with the as-prepared quantum dots to form a nano drug-delivery system through non-covalent interactions. The developed material demonstrated drug loading efficiency of ∼91 % and a very efficient (∼80 %) pH-responsive drug release at pH 5.5. The cytotoxic properties of the developed nano-platform viz. manganese, nitrogen dual-doped carbon quantum dots, and methotrexate conjugated manganese nitrogen dual-doped carbon quantum dot complex were evaluated in cancer cells (HeLa) and healthy human cells (L929). The conjugated complex demonstrated excellent biocompatibility, high cellular uptake, and a substantial drug release. Healthy human cells were largely unaffected when incubated with both the MTX-conjugated Mn-, N-CQD and the free drug. Additionally, in vitro, the fluorescence bio-imaging potential of the developed nano-platform was also assessed, where the unconjugated (free) quantum dots exhibited better blue fluorescence imaging potential compared to that of the conjugated complex, which can be attributed to fluorescence quenching due to the presence of methotrexate. This study highlights the manganese nitrogen dual-doped carbon quantum dots capable of pH-responsive methotrexate drug delivery selective to cancer cells. The combination of drug delivery and fluorescence imaging creates an efficient platform for targeted therapy, allowing very precise drug release while accessing non-invasive monitoring of therapeutic response. This method holds a great promise for advancing cancer treatment strategies, with the potential for increased efficacy and decreased side effects.

Revolutionizing Herbal Medicine: Exploring Nano Drug Delivery Systems

Abstract. Introduction: Traditional herbal medicine has been practiced for centuries and continues to play a significant role in healthcare systems worldwide. However, the efficacy and therapeutic potential of herbal remedies can be limited due to various factors such as poor bioavailability, instability, and non-specific targeting. In recent years, nanotechnology has emerged as a promising approach to overcome these limitations and revolutionize the field of herbal medicine. This review explores the application of nano drug delivery systems in enhancing the effectiveness of herbal therapeutics. The utilization of nanotechnology in the context of herbal medicine involves the design and development of nano-sized carriers that can encapsulate and deliver herbal bioactive compounds to the target sites in a controlled and targeted manner. Various types of nanocarriers, such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, and nanoemulsions, have been extensively investigated for their potential in improving the bioavailability, stability, and controlled release of herbal compounds. The integration of nanotechnology with herbal medicine offers several advantages, including enhanced solubility, protection against degradation, prolonged circulation time, and specific targeting to diseased tissues or cells. Furthermore, nano drug delivery systems can also facilitate the combination of multiple herbal ingredients, enabling synergistic effects and customized therapeutic approaches. This review provides an overview of the recent advancements in nano drug delivery systems for herbal medicine, highlighting their potential applications in various therapeutic areas, such as cancer treatment, neurodegenerative disorders, cardiovascular diseases, and inflammatory conditions. Additionally, challenges and future perspectives regarding the clinical translation of these nanotechnological approaches are discussed. In conclusion, the integration of nanotechnology with herbal medicine holds great promise in revolutionizing the field of healthcare. The development of efficient and targeted nano drug delivery systems can significantly enhance the therapeutic efficacy of herbal remedies, leading to improved patient outcomes and the potential for personalized medicine. Further research and collaborations between scientists, herbalists, and clinicians are needed to unlock the full potential of nano drug delivery systems in herbal medicine. Keywords: Revolutionizing, Herbal medicine, Nano drug delivery systems, Bioavailability, Stability, Nanotechnology, Nanocarriers, Liposomes, Polymeric nanoparticles, Solid lipid nanoparticles, Nanoemulsions

Targeting Wnt-β-Catenin Signaling Pathway for Hepatocellular Carcinoma Nanomedicine.

Hepatocellular carcinoma (HCC) represents a high-fatality cancer with a 5-year survival of 22%. The Wnt/β-catenin signaling pathway presents as one of the most upregulated pathways in HCC. However, it has so far not been targetable in the clinical setting. Therefore, studying new targets of this signaling cascade from a therapeutic aspect could enable reversal, delay, or prevention of hepatocarcinogenesis. Although enormous advancement has been achieved in HCC research and its therapeutic management, since HCC often occurs in the context of other liver diseases such as cirrhosis leading to liver dysfunction and/or impaired drug metabolism, the current therapies face the challenge of safely and effectively delivering drugs to the HCC tumor site. In this review, we discuss how a targeted nano drug delivery system could help minimize the off-target toxicities of conventional HCC therapies as well as enhance treatment efficacy. We also put forward the current challenges in HCC nanomedicine along with some potential therapeutic targets from the Wnt/β-catenin signaling pathway that could be used for HCC therapy. Overall, this review will provide an insight to the current advances, limitations and how HCC nanomedicine could change the landscape of some of the undruggable targets in the Wnt/β-catenin pathway.

Preparation and anti-tumor effects of mesoporous silica nanoparticles loaded with trifluoperazine.

We have developed a targeted nano-drug delivery system that effectively harnesses the anti-tumor properties of trifluoperazine (TFP), while concurrently mitigating its side effects on the central nervous system. The manufacturing process entailed the preparation of mesoporous silica nanoparticles (MSN-NH2), followed by the loading of trifluoperazine into the pores of MSN-NH2 and then surface modification with polyethylene glycol (PEG) and anisamide (AA), resulting in the formation of TFP@MSN@PEG-AA (abbreviated as TMPA) nanoparticles. In vitro and in vivo anti-tumor activity and hemolysis experiments showed that TMPA had an excellent safety profile and a good anti-tumor effect. Importantly, the drug content of the TMPA nanoparticle group was found to be significantly lower than that of the TFP group in the mouse brain tissue as determined by High Performance Liquid Chromatography (HPLC) detection. Therefore, the developed drug delivery system achieved the goal of maintaining TFP's anti-tumor action while avoiding its negative effects on the central nervous system.

Cancer-cell-membrane-camouflaged supramolecular self-assembly of antisense oligonucleotide and chemodrug for targeted combination therapy.

The anti-apoptotic B-cell lymphoma-2 (Bcl-2) family of proteins are critical regulators of cell death that are overexpressed in many cancer cells, especially in multi-drug resistant cancer cells. Combinatorial gene- and chemotherapies using antisense oligonucleotides (ASOs) to suppress the expression of Bcl-2-family mRNA and restore the sensitivity of the cell to chemodrugs provide a promising pathway for anticancer treatment. However, intrinsic differences between macromolecular ASOs and small molecular chemodrugs make their co-delivery challenging. Moreover, extraneous carriers may induce immunogenicity and inflammation problems. Herein, we develop a targeted nanodrug delivery system using the cationic amphiphilic chemodrug mitoxantrone (Mito), which interacts with Bcl-2 ASO through electrostatic interaction and self-assembles into nanoparticles (NP[Bcl-2/Mito]), whose size can be controlled by regulating the ratio of ASO and Mito. NP[Bcl-2/Mito] can protect the ASO from degradation during delivery and combine gene- and chemotherapies to improve the anticancer effect. Furthermore, cancer cell membranes (CCMs) derived from homologous tumors were used to camouflage NP[Bcl-2/Mito] (NP[Bcl-2/Mito]@CCM) to achieve immune escape and tumor targeting. Both in vitro and in vivo assessments demonstrate the excellent performance of NP[Bcl-2/Mito]@CCM for drug-resistant breast tumor therapy. This CCM-camouflaged ASO/chemodrug nanoplatform provides a promising pathway for the targeted delivery of ASOs and chemodrugs for tumor combination therapy.

Chitosan/Gamma-Alumina/Fe3O4@5-FU Nanostructures as Promising Nanocarriers: Physiochemical Characterization and Toxicity Activity.

Today, cancer treatment is an important issue in the medical world due to the challenges and side effects of ongoing treatment procedures. Current methods can be replaced with targeted nano-drug delivery systems to overcome such side effects. In the present work, an intelligent nano-system consisting of Chitosan (Ch)/Gamma alumina (γAl)/Fe3O4 and 5-Fluorouracil (5-FU) was synthesized and designed for the first time in order to influence the Michigan Cancer Foundation-7 (MCF-7) cell line in the treatment of breast cancer. Physico-chemical characterization of the nanocarriers was carried out using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM), dynamic light scattering (DLS), and scanning electron microscopy (SEM). SEM analysis revealed smooth and homogeneous spherical nanoparticles. The high stability of the nanoparticles and their narrow size distribution was confirmed by DLS. The results of the loading study demonstrated that these nano-systems cause controlled, stable, and pH-sensitive release in cancerous environments with an inactive targeting mechanism. Finally, the results of MTT and flow cytometry tests indicated that this nano-system increased the rate of apoptosis induction on cancerous masses and could be an effective alternative to current treatments.

Construction and Biological Evaluation of Multiple Modification Hollow Mesoporous Silicone Doxorubicin Nanodrug Delivery System.

The combination of functionalized nanoparticles and chemotherapy drugs can effectively target tumor tissue, which can improve efficacy and reduce toxicity. In this article, pPeptide-PDA@HMONs-DOX nanoparticles (phosphopeptide-modified polydopamine encapsulates doxorubicin-loaded hollow mesoporous organosilica nanoparticles) were constructed that based on multiple modification hollow mesoporous organosilica nanoparticles (HMONs). The pPeptide-PDA@HMONs-DOX nanoparticles retain the biological functions of phosphorylated peptide while exhibiting biological safety that are suitable for effective drug delivery and stimulus responsive release. The degradation behaviors showed that pPeptide-PDA@HMONs-DOX has dual-responsive to drug release characteristics of pH and glutathione (GSH). In addition, the prepared pPeptide-PDA@HMONs-DOX nanoparticles have good biological safety, and their anti-tumor efficacy was significantly better than doxorubicin (DOX). This provided new research ideas for the construction of targeted nanodrug delivery systems based on mesoporous silicon. Scheme 1 The preparation of pPeptide-PDA@HMONs-DOX and the process of drug release under multiple responses. (A) Schematic diagram of the synthesis process of pPeptide-PDA@HMONs-DOX. (B) The process in which nanoparticles enter the cell and decompose and release DOX in response to pH and GSH.

Application of Nanoparticles in the Treatment of Lung Cancer With Emphasis on Receptors.

Lung cancer is one of the malignant tumors that has seen the most rapid growth in terms of morbidity and mortality in recent years, posing the biggest threat to people’s health and lives. In recent years, the nano-drug loading system has made significant progress in the detection, diagnosis, and treatment of lung cancer. Nanomaterials are used to specifically target tumor tissue to minimize therapeutic adverse effects and increase bioavailability. It is achieved primarily through two mechanisms: passive targeting, which entails the use of enhanced penetration and retention (EPR) effect, and active targeting, which entails the loading recognition ligands for tumor marker molecules onto nanomaterials. However, it has been demonstrated that the EPR effect is effective in rodents but not in humans. Taking this into consideration, researchers paid significant attention to the active targeting nano-drug loading system. Additionally, it has been demonstrated to have a higher affinity and specificity for tumor cells. In this review, it describes the development of research into active targeted nano-drug delivery systems for lung cancer treatment from the receptors’ or targets’ perspective. We anticipate that this study will help biomedical researchers use nanoparticles (NPs) to treat lung cancer by providing more and novel drug delivery strategies or solid ligands.

A success targeted nano delivery to lung cancer cells with multi-walled carbon nanotubes conjugated to bromocriptine

In this research, a new nano drug-based multi-walled carbon nanotubes (MWCNTs) was prepared and evaluated qualitatively. Bromocriptine (BRC) was conjugated to functionalized carbon nanotubes. Then, the CHNS, FT-IR, SEM, and RAMAN tests for characterization of the conjugated drug were done. The nanofluid-containing nano-drug was evaluated on lung cancer cells (A549 & QU-DB) and MRC5 by MTT and flow cytometry tests. Then, the gene expression studies of dopamine receptor genes were done before and after nano-drug treatment. After that, a western blotting test was carried out for further investigation of dopamine receptors protein production. Finally, Bax and Bcl-2 secretion were measured by the ELISA method in cells affected by MWCNTs-BRC Nf compared to untreated cells. The results showed that the nano-drug had a significant lethal effect on cancer cells, while it had no toxicity on MRC5. Also, the nano-drug could significantly induce apoptosis in lung cancer cells at a lower dose compared to the drug alone. In this study, a targeted nano-drug delivery system was designed, and its performance was evaluated based on neurotransmitter pathways, and the results showed that it may be useful in the treatment of lung cancer. However, additional studies on animal models are underway.

Smart Nanotherapeutics and Lung Cancer.

Lung cancer is a significant health problem worldwide. Unfortunately, current therapeutic strategies lack a sufficient level of specificity and can harm adjacent healthy cells. Consequently, to address the clinical need, novel approaches to improve treatment efficiency with minimal side effects are required. Nanotechnology can substantially contribute to the generation of differentiated products and improve patient outcomes. Evidence from previous research suggests that nanotechnology-based drug delivery systems could provide a promising platform for the targeted delivery of traditional chemotherapeutic drugs and novel small molecule therapeutic agents to treat lung cancer cells more effectively. This has also been found to improve the therapeutic index and reduce the required drug dose. Nanodrug delivery systems also provide precise control over drug release, resulting in reduced toxic side effects, controlled biodistribution, and accelerated effects or responses. This review highlights the most advanced and novel nanotechnology-based strategies, including targeted nanodrug delivery systems, stimuli-responsive nanoparticles, and bio-nanocarriers, which have recently been employed in preclinical and clinical investigations to overcome the current challenges in lung cancer treatments.

Thrombolytic Agents: Nanocarriers in Targeted Release.

A thrombus, known as a blood clot, may form within the vascular system of the body and impede blood flow. Thrombosis is the most common underlying pathology of cardiovascular diseases, contributing to high morbidity and mortality. However, the main thrombolytic drugs (urokinase, streptokinase, etc.) have shortcomings, including a short half-life, serious side effects and a lack of targeting, that limit their clinical application. The use of nano-drug delivery systems is expected to address these problems and a variety of approaches, including biological and physical responsive systems, have been explored. In this report, recent advances in the development of targeted nano-drug delivery systems are thoroughly reviewed.

A Targeted Nano Drug Delivery System of AS1411 Functionalized Graphene Oxide Based Composites.

A novel method for the preparation of antitumor drug vehicles has been optimized. Biological materials of chitosan oligosaccharide (CO) and γ‐polyglutamic acid (γ‐PGA) have previously been employed as modifiers to covalently modify graphene oxide (GO), which in turn loaded doxorubicin (DOX) to obtain a nano drug delivery systems of graphene oxide based composites (GO‐CO‐γ‐PGA‐DOX). The system was not equipped with the ability of initiative targeting, thus resulting into toxicity and side effects on normal tissues or organs. In order to further improve the targeting property of the system, the nucleic acid aptamer NH2‐AS1411 (APT) of targeted nucleolin (C23) was used to conjugate on GO‐CO‐γ‐PGA to yield the targeted nano drug delivery system APT‐GO‐CO‐γ‐PGA. The structure, composition, dispersion, particle size and morphology properties of the synthesized complex have been studied using multiple characterization methods. Drug loading and release profile data showed that APT‐GO‐CO‐γ‐PGA is provided with high drug loading capacity and is capable of controlled and sustained release of DOX. Cell experimental results indicated that since C23 was overexpressed on the surface of Hela cells but not on the surface of Beas‐2B cells, APT‐GO‐CO‐γ‐PGA‐DOX can target Hela cells and make increase toxicity to Hela cells than Beas‐2B cells, and the IC50 value of APT‐GO‐CO‐γ‐PGA‐DOX was 3.23±0.04 μg/mL. All results proved that APT‐GO‐CO‐γ‐PGA can deliver antitumor drugs in a targeted manner, and achieve the effect of reducing poison, which indicated that the targeted carrier exhibits a broad application prospect in the field of biomedicine.

Revealing the Dynamic Mechanism by Which Transferrin Promotes the Cellular Uptake of HAIYPRH Peptide-Conjugated Nanostructures by Force Tracing.

The HAIYPRH (T7) peptide has been widely used as a ligand for constructing tumor-targeted nanodrug delivery systems since it can target the transferrin receptor (TfR) and then enter cells easily with the help of transferrin (Tf). However, the dynamic mechanism by which transferrin promotes the entry of T7-conjugated nanostructures into cells remains unclear. Herein, a force tracing technique based on atomic force microscopy (AFM) was used to track the ultrafast dynamic process of a T7-conjugated gold nanoparticle (AuNP-T7) entering a cell at the single-particle level in real time. Tf helped decrease the endocytosis force and increase the endocytosis speed of AuNP-T7 in A549 cells. However, Tf only increased the endocytosis speed of AuNP-T7 in HeLa cells. In contrast, in Vero cells without TfR overexpression, Tf decreased the endocytosis speed. This report provides important insights for redesigning and developing T7-conjugated nanodrug carriers in targeted nanodrug delivery systems.

Direct Quantification of Drug Loading Content in Polymeric Nanoparticles by Infrared Spectroscopy.

Nanotechnology has enabled the development of novel therapeutic strategies such as targeted nanodrug delivery systems, control and stimulus-responsive release mechanisms, and the production of theranostic agents. As a prerequisite for the use of nanoparticles as drug delivery systems, the amount of loaded drug must be precisely quantified, a task for which two approaches are currently used. However, both approaches suffer from the inefficiencies of drug extraction and of the solid-liquid separation process, as well as from dilution errors. This work describes a new, reliable, and simple method for direct drug quantification in polymeric nanoparticles using attenuated total reflection Fourier transform infrared spectroscopy, which can be adapted for a wide variety of drug delivery systems. Silk fibroin nanoparticles and naringenin were used as model polymeric nanoparticle carrier and drug, respectively. The specificity, linearity, detection limit, precision, and accuracy of the spectroscopic approach were determined in order to validate the method. A good linear relation was observed within 0.00 to 7.89% of naringenin relative mass with an R2 of 0.973. The accuracy was determined by the spike and recovery method. The results showed an average 104% recovery. The limit of detection and limit of quantification of the drug loading content were determined to be 0.3 and 1.0%, respectively. The method’s robustness is demonstrated by the notable similarities between the calibrations carried out using two different equipment setups at two different institutions.

Targeted nano-drug delivery system for glioblastoma therapy: In vitro and in vivo study

This study developed polymeric nanoparticles (NPs) conjugated with monoclonal antibody (mAb) for glioblastoma treatment. In this study, the physicochemical properties of poly (butyl cyanoacrylate) (PBCA) NPs were characterized. The cytotoxicity of NPs conjugated with mAb (NPs + mAb) and in vitro drug release evaluation was tested on glioblastoma cell lines. Their therapeutic efficiency and side effects were then assessed in vivo in a rat model of glioblastoma. The conjugation of NPs to mAb revealed an average particle size of 365 nm and conjugation efficiency of 41.95%. The findings also showed that cytotoxicity was augmented by 40% compared to the free form of carboplatin. Moreover, in vivo studies showed that body weight remained relatively stable in rats treated by NPs + mAb and their survival time was longer (23.5 days) compared to rats treated with free carboplatin (19.5 days). In addition, ex vivo investigation showed that rats administered with NPs + mAb exhibited less side effects in the brain, kidney and liver compared to other groups.