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1

Cancer therapeutics strategy using nano-carrier mediated natural drugs

Shaw S., Singh P., Mishra R., Singh R., Nayak R., Bose S.

Journal of Achievements in Materials and Manufacturing Engineering

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2022

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Vol. 114, nr 1

32--41

EN

Purpose: Nucleolin is a multifactorial protein, having a significant role in chromatin remodelling, mRNA stability, ribosome biogenesis, stemness, angiogenesis, etc., thus, it is potential therapeutic target in cancer. The purpose of this paper is to study porous silicon (pSi) nanocarrier-based natural drug delivery system targeting dysregulated nucleolin expression for cancer therapeutics. Design/methodology/approach: Quercetin was loaded in pre-synthesized and characterized pSi nanoparticles, and release kinetics was studied. The study compared the inhibitory concentration (IC50) of quercetin, synthetic drug doxorubicin, and quercetin-loaded pSi nanoparticles. Further, mRNA expression of a target gene, nucleolin, was tested with a quercetin treated breast cancer cell line (MCF-7). Findings: Quercetin-loaded pSi nanoparticles followed first-order release kinetics. IC50 was determined at concentrations of 312 nM, 160 μM, and 50 μM against doxorubicin, quercetin, and quercetin-loaded pSi nanoparticles, respectively. The results further indicated 16-fold downregulation of nucleolin mRNA expression after 48h of quercetin treatment of exponentially growing MCF-7 cells. Research limitations/implications: Whether pSi nanoparticle loaded quercetin can significantly downregulate nucleolin protein expression and its impact on apoptosis, cell proliferation, and angiogenic pathways need further investigation. Practical implications: The practical application of the proposed nanocarrier-based drug delivery system potentially lays out a path for developing targeted therapy against nucleolin-dysregulated cancer using natural products to minimize the side effects of conventional chemotherapeutic drugs. Originality/value: Inhibition of nucleolin and nucleolin regulated pathways using natural compounds and its targeted delivery with nanocarrier is not yet done.

2

Znaczenie nowoczesnej diagnostyki molekularnej w terapii przeciwnowotworowej

Mazur Bogdan, Żydowicz Grzegorz

Laboratorium Medyczne

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2020

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nr 2-3

72--75

PL

W ostatnim dziesięcioleciu w Polsce zapadalność na choroby nowotworowe wzrosła o prawie 28%, przy niezmiennym rozkładzie najliczniej występujących nowotworów. Liczba zgonów związanych z rakiem wzrosła znacząco mniej (7%). Przedstawiono wybór akceptowanych terapii celowanych, wskazując na potrzebę multidyscyplinarnego podejścia do diagnostyki i planowania terapii. Metody osiągnięcia skrócenia oczekiwania na podjęcie skutecznej terapii, na podstawie dostępnego piśmiennictwa, upatruje się w uproszczeniu i uporządkowaniu procedur przepływu informacji oraz wyboru najprostszych, najkrótszych, a jednocześnie pewnych metod diagnostyki molekularnej.

EN

During the last decade, the incidence rate of cancer diseases in Poland has increased by almost 28%, while the distribution of the most frequent neoplasms has remained unchanged. In this period, an increase in cancer-related deaths has been significantly lower (7%). This paper presents commonly accepted modern targeted therapies, indicating the need for a multidisciplinary approach to proper diagnostics and therapy planning. Based on the available literature it can be concluded, that the simplification of procedures, organising the flow of data and the selection of the simplest, shortest and most reliable molecular diagnostic methods are the best ways to reduce waiting time for treatment.

3

Nanonośniki jako nowoczesne transportery w kontrolowanym dostarczaniu leków

Niemirowicz K., Car H.

Chemik

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2012

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Vol. 66, nr 8

868-881

PL

W systemie kontrolowanego dostarczania leków na poziomie nanocząstek (NP) wykorzystuje się różne ugrupowania, w tym polimery, materiały węglowe oraz nanocząstki magnetyczne. Wymienione związki, występują w postaci prostego nośnika lub stanowią otoczkę typu core - shell, np. na rdzeniu magnetycznym. Taka modyfikacja pozwala na kontrolowany transport w miejsce docelowe, a także obrazowanie zachodzących w tkance procesów desorpcji leku. W niniejszym artykule zostanie przedstawiona synteza nośników leków, funkcjonalizacja ich powierzchni oraz sposoby immobilizacji związków aktywnych na ich powierzchni ze szczególnym uwzględnieniem materiałów magnetycznych.

EN

In drug delivery systems there are many different groups used at the level of nanoparticles (NP), including polymers, carbon materials and magnetic nanoparticles. The above-mentioned compounds occur in the form of a simple carrier or make a complex core - shell system, e.g. on a magnetic core. This modification allows for a controlled drug delivery to a target site as well as imaging the celllevel drug desorption processes. This paper presents the process of synthesising the drug carriers, functionalising their surfaces and the methods for immobilising active substances on their surface with special emphasis given to magnetic materials.

4

Chemiczne aspekty celowanej terapii przeciwnowotworowej I. Kowalencyjne połączenia ligand-nośnik

Werengowska K. M., Wiśniewski M., Terzyk A.P., Gurtowska N., Drewa T. A.

Wiadomości Chemiczne

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2011

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[Z] 65, 9-10

887-915

EN

In this study we describe the most popular biomedical engineering nanoparticles including carbon nanotubes [17-20], liposomes [4-7], polymeric micells [11-13], quantum dots [3, 21-23], hydrogels [24-27], dendrimers [14-16] which are recently considered as modern drug carriers. These nanomaterials are applied for cancer diagnostic and targeted delivery of active compounds as chemotherapeutics in so called targeted therapy. Thus, we characterized the ideas of targeted therapy for which compositions of carriers with antibody are constructed (Figs. 3, 4). We also compared the traditional and targeted mechanisms [1, 3, 28-29] of drug delivery (Fig. 2). During targeted therapy only the essential dose of drug (less than during conventional chemotherapy) is delivering to the cancer cell. In additional, the application of targeted therapy reduces side effects, being very characteristic for the traditional treatment. The anticancer compound can selectively hits the target only, due to the presence of the ligands attached to the surface of nanocarirer. We characterized ligands which are often use in nanomedicine: antibodies [33-37], folic acid [30-33], peptides [33, 38, 39], aptamers [33, 40, 41] and transferrin [33, 42-44]. The purpose of this study is description of the bioconjugation of ligand-nanocarrier. This step is necessary and very important in synthesis of the novel drug delivery systems in targeted anticancer therapy. We report recent advances in the field showing the formation of amides (Figs. 6-8) [51-57], thioethers (Figs. 9-11) [52, 60-66], disulfides (Fig. 12) [69], and acethyl-hydrazone groups (Fig. 13) [73]. Special attention is paid to the process such as Diels-Alder (Figs. 14, 15) [74, 75] and "click chemistry" through the cycloaddition of Huisgen (Figs. 16, 17) [79-82]. We describe also the reaction of Staudinger [83] and the process of formation Schiff 's base [84]. The processes enable very mild and selective modification of the carriers through formation of amide bound. These methods ware less popular but allow the fictionalization of nanocarriers in biomedical application. Each reaction or process needs special and individual environment and conditions, which are summarized in Table 1.

5

Development of 153Sm-DTPA-rituximab for radioimmunotherapy

Bahrami-Samani A., Ghannadi-Maragheh M., Jalilian A. R., Yousefnia H., Garousi J., Moradkhani S.

Nukleonika

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2009

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Vol. 54, No. 4

271-277

EN

Combining beta-particle effect with therapeutic properties of anti-CD20 monoclonal antibody in lymphomas, Mabthera™ (rituximab) was targeted in this study. The antibody was labeled with 153Sm-samarium chloride (185 MBq) after conjugation with freshly prepared ccDTPA. Conjugated-rituximab was obtained by the addition of 1 ml of a rituximab pharmaceutical solution (5 mg/ml, in phosphate buffer, pH = 7.8) to a glass tube precoated with freshly prepared ccDTPA (0.01–0.1 mg) at 25 degrees centigrade. Sm-153 chloride was obtained by a thermal neutron flux (5 × 1013 nźcm–2źs–1) of an enriched 152Sm2O3 sample, dissolved in acidic media. Radiolabeling was performed in one hour by the addition of DTPA-rituximab conjugate at room temperature. Radiochemical purity of 96% (ITLC) and 98% (HPLC) were obtained for the final radioimmunoconjugate (specific activity = 120 TBq/mmol). The final isotonic 153Sm-rituximab complex was checked by gel electrophoresis for protein integrity retention. Biodistribution studies in normal rats were performed to determine radioimmunoconjugate distribution up to 24 h. SPECT images were also obtained using 103 keV photons up to 48 h.

6

Production of [103Pd]Bleomycin complex for targeted therapy

Jalilian A., Yari-Kamrani Y., Sadeghi M.

Nukleonika

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2006

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Vol. 51, nr 2

119-123

EN

Due to the anticancer properties of bleomycin (BLM) complexes, production of [103Pd]bleomycin ([103Pd]BLM) was targeted. Palladium-103 (T1/2 = 16.96 d) was produced via the 103Rh(p,n)103Pd nuclear reaction using a natural rhodium target. Proton energy was 18 MeV with 200 mA irradiation for 15 h (final activity 25.9 GBq of 103Pd2+, RCP > 95%, radionuclidic purity > 99%). 103Pd was separated from the irradiated target by anion exchange using a Dowex 1´8 (Cl-)/100-200 mesh resin in the form of Pd(NH3)2Cl2 in order to react with bleomycin to yield [103Pd]BLM. Chemical purity of the final product was in accordance to the accepted limits. [103Pd]BLM was prepared with a radiochemical yield of more than 98% at 80°C in 30 min. The labeling reaction was optimized for time, temperature and ligand concentration. Radiochemical purity of more than 99% was obtained using RTLC with specific activity of about 370 MBq/mmol. The stability of the tracer was checked in the final product and presence of human serum at up to 3 h. The complex was stable in human serum at 37°C up to 2 h of incubation. Biodistribution studies using a SPECT system performed in normal rats in the first 2-3 h.