scholarly journals Lipid Nanostructured Particles as Emerging Carriers for Targeted Delivery of Bioactive Molecules: Applications in Food and Biomedical Sciences (An Overview)

2020 ◽  
Vol 77 (1) ◽  
pp. 37
Author(s):  
Patricia MUNTEAN ◽  
Carmen SOCACIU ◽  
Mihai Adrian SOCACIU
Keyword(s):  
Targeted Delivery ◽  
Drug Carriers ◽  
Lipid Nanoparticles ◽  
Bioactive Molecules ◽  
Biomedical Sciences ◽  
Nanostructured Particles ◽  
Drug Conjugates ◽  
Carrier Systems

Lipid nanoparticles are getting a growing scientific and technological interest, worldwide. Either Solid Lipid Nanoparticles (SLNs), Nanostructured Lipid Carriers (NLCs), Lipid Drug Conjugates (LDCs) or Polymer-Lipid Nanoparticles (PLNs) have been produced and investigated last years, being reccomended as emerging carrier systems for many food and biomedical applications. An overview of the last publications, mainly since 2017 is presented, underlying the most important methods and techniques used for their preparation (e.g. high shear homogenization in hot and cold conditions, ultrasound assisted melt emulsification) as well techniques applied for measuring the size, calorimetric properties, zeta-potential, etc. Most relevant data related to the use of food-grade ingredients and designed lipid nanoparticles as delivery systems for organic and inorganic bioactive molecules in food or packaging’s are presented. The major reason for this trend in food science is the aim to overcome problems associated with the low bioavailability of many lipophilic bioactive compounds which are claimed to bring benefits to human health (carotenoid or anthocyanin pigments, sterols, vitamins). Finally, the recent applications of different formulas of lipid nanoparticles as drug carriers for in vitro experiments or for in vivo therapy (oral, parenteral or transdermal formulas) are presented.

scholarly journals Single Domain Antibodies as Carriers for Intracellular Drug Delivery: A Proof of Principle Study

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 927
Author(s):  
Sebas D. Pronk ◽  
Erik Schooten ◽  
Jurgen Heinen ◽  
Esra Helfrich ◽  
Sabrina Oliveira ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Single Domain ◽  
Drug Conjugates ◽  
Intracellular Drug Delivery ◽  
Internalization Rate ◽  
Single Domain Antibodies ◽  
Different Characteristics

Antibody-drug conjugates (ADCs) are currently used for the targeted delivery of drugs to diseased cells, but intracellular drug delivery and therefore efficacy may be suboptimal because of the large size, slow internalization and ineffective intracellular trafficking of the antibody. Using a phage display method selecting internalizing phages only, we developed internalizing single domain antibodies (sdAbs) with high binding affinity to rat PDGFRβ, a receptor involved in different types of diseases. We demonstrate that these constructs have different characteristics with respect to internalization rates but all traffic to lysosomes. To compare their efficacy in targeted drug delivery, we conjugated the sdAbs to a cytotoxic drug. The conjugates showed improved cytotoxicity correlating to their internalization speed. The efficacy of the conjugates was inhibited in the presence of vacuolin-1, an inhibitor of lysosomal maturation, suggesting lysosomal trafficking is needed for efficient drug release. In conclusion, sdAb constructs with different internalization rates can be designed against the same target, and sdAbs with a high internalization rate induce more cell killing than sdAbs with a lower internalization rate in vitro. Even though the overall efficacy should also be tested in vivo, sdAbs are particularly interesting formats to be explored to obtain different internalization rates.

Toxicity Effects of Anthracycline-Converted Herceptin and Azo-Functionalized Fe3O4 Nanoparticles on the Heart of Patients with Breast Cancer Based on Echocardiography

2021 ◽  
Vol 21 (2) ◽  
pp. 878-885
Author(s):  
Li Liu ◽  
Tingting Shen ◽  
Hongfang Liu ◽  
Gen Zhang ◽  
Yongfu Shao
Keyword(s):  
Breast Cancer ◽  
Targeted Delivery ◽  
Combined Therapy ◽  
Drug Carriers ◽  
Temperature Sensitive ◽  
Breast Cancer Patients ◽  
Clinical Value ◽  
Low Toxicity

The multifunctional nano-carrier system can simultaneously achieve multiple functions such as diagnostic imaging, targeted delivery of anti-tumor drugs, and combined therapy. Application potential Fe3O4 magnetic nanoparticles have the characteristics of low toxicity, superparamagnetism and good photothermal properties. Therefore, a multifunctional magnetic nanocarrier with both magnetic targeting and photothermal properties can be prepared by surface modification of Fe3O4 o DOX is an anti-tumor drug widely used in clinical treatment, and its severe toxic and side effects greatly limit its application. In this paper, a temperature-sensitive magnetic nanocarrier was first constructed and proved to have good superparamagnetism, photothermal properties, and biocom-patibility Then, Fe3O4-Azo-DOX drug-loaded nanoparticles were constructed by covalently bonding DOX. The prepared Fe3O4-Azo-DOX nanoparticles have high stability, sensitive photothermal response and low toxicity. Finally, Fe3O4-Azo-DOX was applied to the study of combined photother-motherapy and chemotherapy in vitro and in vivo. Based on Fe3O4 nanoparticles, a temperature-sensitive Fe3O4-Azo nanocarrier was constructed and its related properties were characterized. Furthermore, anthracycline nanodrugs were used in chemotherapy of breast cancer patients, and their effects were analyzed according to echocardiography parameter change. The results show that Fe3O4-Azo nanoparticles have a good photothermal heating effect. MCF-7 breast cancer cells were selected as a model to investigate the cytotoxicity of Fe3O4-Azo. The results proved that they have excellent biocompatibility and can be used as drug carriers. A Fe3O4-Azo nanocarrier was used to load DOX to construct a NIR-responsive nano-drug delivery system. By studying the NIR controlled release of Fe3O4-Azo-DOX under different pH conditions, it can be seen that it has NIR-responsive release function and the best release effect at pH 5.7. It was found that LVEF, LVFS, and E/A were significantly lower after chemotherapy than before (P < 0.05), which had a certain clinical value in cardiotoxicity The in vitro antitumor effect of Fe3O4-Azo-DOX was studied, and the results showed that the combined effect of photothermal-chemotherapy was significantly better than the photothermal treatment based on Fe3O4-Azo carrier alone and the chemotherapy based on free DOX alone.

scholarly journals Programmably tiling rigidified DNA brick on gold nanoparticle as multi-functional shell for cancer-targeted delivery of siRNAs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chang Xue ◽  
Shuyao Hu ◽  
Zhi-Hua Gao ◽  
Lei Wang ◽  
Meng-Xue Luo ◽  
...  
Keyword(s):  
Gold Nanoparticle ◽  
Targeted Delivery ◽  
Target Genes ◽  
Sirna Delivery ◽  
Three Dimensional ◽  
Drug Carriers ◽  
High Serum ◽  
Exterior Surface

AbstractSmall interfering RNA (siRNA) is an effective therapeutic to regulate the expression of target genes in vitro and in vivo. Constructing a siRNA delivery system with high serum stability, especially responsive to endogenous stimuli, remains technically challenging. Herein we develop anti-degradation Y-shaped backbone-rigidified triangular DNA bricks with sticky ends (sticky-YTDBs) and tile them onto a siRNA-packaged gold nanoparticle in a programmed fashion, forming a multi-functional three-dimensional (3D) DNA shell. After aptamers are arranged on the exterior surface, a biocompatible siRNA-encapsulated core/shell nanoparticle, siRNA/Ap-CS, is achieved. SiRNAs are internally encapsulated in a 3D DNA shell and are thus protected from enzymatic degradation by the outermost layer of YTDB. The siRNAs can be released by endogenous miRNA and execute gene silencing within tumor cells, causing cell apoptosis higher than Lipo3000/siRNA formulation. In vivo treatment shows that tumor growth is completely (100%) inhibited, demonstrating unique opportunities for next-generation anticancer-drug carriers for targeted cancer therapies.

scholarly journals Small Molecule-Based Prodrug Targeting Prostate Specific Membrane Antigen for the Treatment of Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 417
Author(s):  
Xinning Wang ◽  
Aditi Shirke ◽  
Ethan Walker ◽  
Rongcan Sun ◽  
Gopolakrishnan Ramamurthy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Small Molecule ◽  
Targeted Delivery ◽  
Treatment Options ◽  
Maximum Tolerated Dose ◽  
In Vivo Studies ◽  
Castration Resistant Prostate Cancer ◽  
Drug Conjugates

Metastatic castration-resistant prostate cancer poses a serious clinical problem with poor outcomes and remains a deadly disease. New targeted treatment options are urgently needed. PSMA is highly expressed in prostate cancer and has been an attractive biomarker for the treatment of prostate cancer. In this study, we explored the feasibility of targeted delivery of an antimitotic drug, monomethyl auristatin E (MMAE), to tumor tissue using a small-molecule based PSMA lig-and. With the aid of Cy5.5, we found that a cleavable linker is vital for the antitumor activity of the ligand–drug conjugate and have developed a new PSMA-targeting prodrug, PSMA-1-VcMMAE. In in vitro studies, PSMA-1-VcMMAE was 48-fold more potent in killing PSMA-positive PC3pip cells than killing PSMA-negative PC3flu cells. In in vivo studies, PSMA-1-VcMMAE significantly inhibited tumor growth leading to prolonged animal survival in different animal models, including metastatic prostate cancer models. Compared to anti-PSMA antibody-MMAE conjugate (PSMA-ADC) and MMAE, PSMA-1-VcMMAE had over a 10-fold improved maximum tolerated dose, resulting in improved therapeutic index. The small molecule–drug conjugates reported here can be easily synthesized and are more cost efficient than anti-body–drug conjugates. The therapeutic profile of the PSMA-1-VcMMAE encourages further clin-ical development for the treatment of advanced prostate cancer.

Tumor-on-Chip: Simulation of Complex Transport Around Tumor

2013 ◽  
Author(s):  
Bongseop Kwak ◽  
Kinam Park ◽  
Bumsoo Han
Keyword(s):  
Animal Models ◽  
Targeted Delivery ◽  
Fluid Pressure ◽  
Drug Carriers ◽  
Microfluidic System ◽  
Tissue Interactions ◽  
Transport Barriers ◽  
In Vitro Cell Cultures

Nanoparticles (NP) offer great potential as drug carriers for targeted delivery to tumor by increasing the delivery efficacy and reducing non-specific accumulation at non-targeted sites [1]. Despite these promising early outcomes [2], the NP delivery to target tumor site is still significantly limited due to complex in vivo transport barriers [3–5]. In order to improve the in vivo delivery efficacy, the NPs should be designed considering all these complex transport barriers beyond currently used enhanced permeation and retention (EPR) effect [6]. However, testing of NP delivery are primarily based on simple 2D or 3D in vitro cell cultures or animal models. However, these static 2D or 3D tumor models oversimplify the actual in vivo tumor environment including the absence of tissue-tissue interactions such as blood-endothelium, endothelium-intersititum, high interstitial fluid pressure, and interstitium-lymphatics [2, 3]. The animal models can provide the testbed with these tissue-tissue interactions, but it is very difficult to establish quantitative understanding of the NP transport at these tissue-tissue interfaces. To address these challenges and bridge the in vitro static models with the animal models, here we developed a 3D multi-layered microfluidic system that mimics the tissue-tissue interactions at tumor microenvironment is developed. The system is then used to investigate the transvascular and interstitial transport of NPs in tumor.

99mTc(I) carbonyl-radiolabeled lipid based drug carriers for temozolomide delivery and bioevaluation by in vitro and in vivo

2019 ◽  
Vol 107 (12) ◽  
pp. 1185-1193
Author(s):  
Kadir Arı ◽  
Eser Uçar ◽  
Çiğdem İçhedef ◽  
Ayfer Yurt Kılçar ◽  
Emin İlker Medine ◽  
...  
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Drug Carriers ◽  
Lipid Nanoparticles ◽  
Biological Behavior ◽  
Albino Rats ◽  
Target Tissue ◽  
Preclinical Research ◽  
Solid Lipid

Abstract In preclinical research radiolabeled nanoparticles have been attracting interest as a new class of imaging probes. Assuming good stability of solid lipid nanoparticles (SLNs) under physiological conditions, radiolabeled SLNs can be used for imaging and measuring uptake in target tissue. Present study was performed to evaluate biological behavior of temozolomide (TMZ) loaded solid lipid nanoparticles (SLN-TMZ) in vivo and in vitro. Lipid nanoparticles were prepared by emulsification and low-temperature solidification method. ζ potential, morphology and particle size of nanoparticles were determined. Biological behavior of 99mTc(CO)3+ radiolabeled SLN-TMZ were investigated in vitro on U87/Daoy cell lines and in vivo on female Wistar Albino rats. Obtained results of in vitro incorporation, in vivo biodistribution and gamma imaging studies on radiolabeled SLN-TMZ show that the radiolabeled solid lipid nanoparticles could have potential as a drug delivery system for TMZ.

Internal and External Triggering Mechanism of “Smart” Nanoparticle-Based DDSs in Targeted Tumor Therapy

2018 ◽  
Vol 24 (15) ◽  
pp. 1639-1651 ◽  
Author(s):  
Xian-ling Qian ◽  
Jun Li ◽  
Ran Wei ◽  
Hui Lin ◽  
Li-xia Xiong
Keyword(s):  
Targeted Delivery ◽  
Tumor Therapy ◽  
Burst Release ◽  
Tumor Site ◽  
Chemotherapeutic Drugs ◽  
Triggering Mechanism ◽  
Triggering Factors ◽  
Or Genes

Background: Anticancer chemotherapeutics have a lot of problems via conventional Drug Delivery Systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: “passive”, “active”, and “smart” targeting. Objective: To summarize the mechanisms of various internal and external “smart” stimulating factors on the basis of findings from in vivo and in vitro studies. Method: A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Results: Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), “smart” DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. Conclusion: In this review article, we summarize and classify the internal and external triggering mechanism of “smart” nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding.

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