Efficient intravesical therapy of bladder cancer with cationic doxorubicin nanoassemblies

Jin, Xun; Zhang, Peilan; Luo, Li; Cheng, Hao; Li, Yunzu; Du, Ting; Zou, Bingwen; Gou, Maling

doi:10.2147/ijn.s103994

Cited by 28 publications

(5 citation statements)

References 31 publications

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“…Collectively, the obtained data indicate a slight cardiotoxic effect of Doxorubicin during its intravesical administration, which, in general, correlates with the literature data describing the clinical efficacy of this method of administration [6]. However, in our opinion, for a more detailed assessment of the state of the myocardium, it is necessary to further investigate the dynamics of changes in the electrophysiological activity of the heart, as well as biochemical markers of its damage.…”

Section: Discussionsupporting

confidence: 84%

Morphological changes in the heart of rats after serial intravesical administration of Doxorubicin

Kostiuk

Hodovan

Gormash³

et al. 2021

Rep. of Morph.

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Along with a pronounced antitumor effect, Doxorubicin causes systemic effects with damage to vital organs, including the heart. It prompts the search for ways to prevent the cardiotoxic effect of the drug, one of which could be its intravesical administration. The aim of the study was to develop a method of serial intravesical administration of Doxorubicin in medium therapeutic doses in an experiment and to evaluate the cardiotoxic effect of the drug. 42 female Wistar rats were included in the study. The control group consisted of 7 intact rats. The experimental group consisted of 35 rats who received intravesical chemotherapy with Doxorubicin at a dose of 5 mg/kg once a week for 5 weeks. On days 7th, 14th, 21st, 28th, 35th the hearts of experimental animals were taken for morphological examination. Histomorphometrically determined: the diameter of cardiomyocytes (in the middle part) and the transverse diameter of their nucleus, the width of the interstitial space (endo- and perimysium). The data of histomorphological and histomorphometric examination of the myocardium testified that all animals of the experimental group had a circulatory disorder in the heart muscle at the level of hemomicrocirculation. Such changes led to cardiomyocyte hypotrophy, interstitial edema and fibrosis. During intravesical chemotherapy, the animals showed marked changes in the myocardium, such as expansion of the endomysial zone, due to capillary congestion and edema, in comparison with animals of the intact group. At the end of the experiment, the animals of the experimental group retained the expansion of the endomysial zone, mainly due to interstitial fibrosis. Such changes indicate myocardial hypoxemia with damage and death of cardiomyocytes, activation of interstitial and replacement collagen formation. The obtained morphological data partially indicate the development of dilated cardiomyopathy in experimental animals. However, these changes were less pronounced than the previously described changes that occur after systemic administration of the drug. Additional studies of the electrophysiological activity of the heart and biochemical markers will make it possible to fully assess the degree of cardiotoxicity of Doxorubicin after its intravesical administration. Thus, serial intravesical administration of Doxorubicin in moderate therapeutic doses according to the proposed method causes changes in the myocardium of experimental animals, which are partially similar to the changes in the heart of people receiving chemotherapy with this drug.

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Section: Discussionsupporting

confidence: 84%

Morphological changes in the heart of rats after serial intravesical administration of Doxorubicin

Kostiuk

Hodovan

Gormash³

et al. 2021

Rep. of Morph.

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“…Another study load epirubicin with poly(ethyl-2-cyanoacrylate)(PECA) NPs and demonstrated that this system could provide sustained drug tissue concentrations and significant cytotoxicity in human BC cells [ 67 ]. Jin et al encapsulated doxorubicin (Dox) with another cationic nanoparticle and significantly improved the efficiency of Dox in orthotopic BC model [ 68 ].…”

Section: Bladder Cancer Treatment and Nanotechnologymentioning

confidence: 99%

Application of nanotechnology in the diagnosis and treatment of bladder cancer

Luo

Wang

et al. 2021

J Nanobiotechnol

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Bladder cancer (BC) is a common malignancy in the genitourinary system and the current theranostic approaches are unsatisfactory. Sensitivity and specificity of current diagnosis methods are not ideal and high recurrence and progression rates after initial treatment indicate the urgent need for management improvements in clinic. Nanotechnology has been proposed as an effective method to improve theranosis efficiency for both non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). For example, gold nanoparticles (AuNPs) have been developed for simple, fast and sensitive urinary sample test for bladder cancer diagnosis. Nanoparticles targeting bladder cancers can facilitate to distinguish the normal and abnormal bladder tissues during cystoscopy and thus help with the complete removal of malignant lesions. Both intravenous and intravesical agents can be modified by nanotechnology for targeted delivery, high anti-tumor efficiency and excellent tolerability, exhibiting encouraging potential in bladder cancer treatment. Photosensitizers and biological agents can also be delivered by nanotechnology, intermediating phototherapy and targeted therapy. The management of bladder cancer remained almost unchanged for decades with unsatisfactory effect. However, it is likely to change with the fast-developed nanotechnology. Herein we summarized the current utility of nanotechnology in bladder cancer diagnosis and treatment, providing insights for the future designing and discovering novel nanoparticles for bladder cancer management. Graphical Abstract

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“…5-FU, DOX and EPI with a broad antineoplastic spectrum are used to treat many different types of cancer as colon or rectum, breast, liver, bladder and brain [ 50 , 61 , 79 , 80 ]. The main drawbacks of direct chemotherapy with these agents can be listed as severe depression of hematopoiesis (anemia, leucopenia, thrombopenia), infection and cardiotoxicity regarding EPI [ 50 ], 5-FU resistance and rapid clearance from the body [ 6 ] and DOX cumulative cardiotoxicity and nephrotoxicity [ 82 ]. Overall, these severe side effects had a deep impact on the mortality rate of cancer patients [ 83 ].…”

Section: State Of the Artmentioning

confidence: 99%

Developments of Smart Drug-Delivery Systems Based on Magnetic Molecularly Imprinted Polymers for Targeted Cancer Therapy: A Short Review

Sanadgol

Wackerlig

2020

Pharmaceutics

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Cancer therapy is still a huge challenge, as especially chemotherapy shows several drawbacks like low specificity to tumor cells, rapid elimination of drugs, high toxicity and lack of aqueous solubility. The combination of molecular imprinting technology with magnetic nanoparticles provides a new class of smart hybrids, i.e., magnetic molecularly imprinted polymers (MMIPs) to overcome limitations in current cancer therapy. The application of these complexes is gaining more interest in therapy, due to their favorable properties, namely, the ability to be guided and to generate slight hyperthermia with an appropriate external magnetic field, alongside the high selectivity and loading capacity of imprinted polymers toward a template molecule. In cancer therapy, using the MMIPs as smart-drug-delivery robots can be a promising alternative to conventional direct administered chemotherapy, aiming to enhance drug accumulation/penetration into the tumors while fewer side effects on the other organs. Overview: In this review, we state the necessity of further studies to translate the anticancer drug-delivery systems into clinical applications with high efficiency. This work relates to the latest state of MMIPs as smart-drug-delivery systems aiming to be used in chemotherapy. The application of computational modeling toward selecting the optimum imprinting interaction partners is stated. The preparation methods employed in these works are summarized and their attainment in drug-loading capacity, release behavior and cytotoxicity toward cancer cells in the manner of in vitro and in vivo studies are stated. As an essential issue toward the development of a body-friendly system, the biocompatibility and toxicity of the developed drug-delivery systems are discussed. We conclude with the promising perspectives in this emerging field. Areas covered: Last ten years of publications (till June 2020) in magnetic molecularly imprinted polymeric nanoparticles for application as smart-drug-delivery systems in chemotherapy.

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Efficient intravesical therapy of bladder cancer with cationic doxorubicin nanoassemblies

Cited by 28 publications

References 31 publications

Morphological changes in the heart of rats after serial intravesical administration of Doxorubicin

Morphological changes in the heart of rats after serial intravesical administration of Doxorubicin

Application of nanotechnology in the diagnosis and treatment of bladder cancer

Developments of Smart Drug-Delivery Systems Based on Magnetic Molecularly Imprinted Polymers for Targeted Cancer Therapy: A Short Review

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