Smart Nanocarriers as an Emerging Platform for Cancer Therapy: A Review

Kenchegowda, Madhuchandra; Rahamathulla, Mohamed; Hani, Umme; Begum, M. Yasmin; Guruswamy, Sagar; Osmani, Riyaz Ali M.; Gowrav, M P; Alshehri, Sultan; Ghoneim, Mohammed M.; Alshlowi, Areej; Gowda, Devegowda Vishakante

doi:10.3390/molecules27010146

Cited by 77 publications

(40 citation statements)

References 201 publications

(208 reference statements)

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“…Besides PROTACs, nanoparticle-based drug delivery systems have the potential for improving the current anticancer therapies, as they offer several advantages including enhanced solubility, bioavailability, and stability of the carried drugs [ 210 ]. Nanocarriers could enhance the efficacy of drugs by optimizing their biochemical and pharmacokinetic characteristics.…”

Section: New Strategies For Targeting Gsk-3 In Cancer Cellsmentioning

confidence: 99%

Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies

Martelli

Paganelli

Evangelisti

et al. 2022

Cells

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Glycogen synthase kinase-3 (GSK-3) is an evolutionarily conserved, ubiquitously expressed, multifunctional serine/threonine protein kinase involved in the regulation of a variety of physiological processes. GSK-3 comprises two isoforms (α and β) which were originally discovered in 1980 as enzymes involved in glucose metabolism via inhibitory phosphorylation of glycogen synthase. Differently from other proteins kinases, GSK-3 isoforms are constitutively active in resting cells, and their modulation mainly involves inhibition through upstream regulatory networks. In the early 1990s, GSK-3 isoforms were implicated as key players in cancer cell pathobiology. Active GSK-3 facilitates the destruction of multiple oncogenic proteins which include β-catenin and Master regulator of cell cycle entry and proliferative metabolism (c-Myc). Therefore, GSK-3 was initially considered to be a tumor suppressor. Consistently, GSK-3 is often inactivated in cancer cells through dysregulated upstream signaling pathways. However, over the past 10–15 years, a growing number of studies highlighted that in some cancer settings GSK-3 isoforms inhibit tumor suppressing pathways and therefore act as tumor promoters. In this article, we will discuss the multiple and often enigmatic roles played by GSK-3 isoforms in some chronic hematological malignancies (chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, and B-cell non-Hodgkin’s lymphomas) which are among the most common blood cancer cell types. We will also summarize possible novel strategies targeting GSK-3 for innovative therapies of these disorders.

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Section: New Strategies For Targeting Gsk-3 In Cancer Cellsmentioning

confidence: 99%

Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies

Martelli

Paganelli

Evangelisti

et al. 2022

Cells

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“…Colon cancer, breast cancer, and lung cancer are the most common cancers affecting women, accounting for almost 50%. Breast cancer is the most commonly diagnosed cancer worldwide, accounting for around 30% of all common cancers [1][2][3][4]. Breast cancer is usually diagnosed in one among eight women worldwide.…”

Section: Introductionmentioning

confidence: 99%

Development and Characterization of Oral Raft Forming In Situ Gelling System of Neratinib Anticancer Drug Using 32 Factorial Design

et al. 2022

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Neratinib (NTB) is an irreversible inhibitor of pan-human epidermal growth factor receptor (HER-2) tyrosine kinase and is used in the treatment of breast cancer. It is a poorly aqueous soluble drug and exhibits extremely low oral bioavailability at higher pH, leading to a diminishing of the therapeutic effects in the GIT. The main objective of the research was to formulate an oral raft-forming in situ gelling system of NTB to improve gastric retention and drug release in a controlled manner and remain floating in the stomach for a prolonged time. In this study, NTB solubility was enhanced by polyethylene glycol (PEG)-based solid dispersions (SDs), and an in situ gelling system was developed and optimized by a two-factor at three-level (32) factorial design. It was analyzed to study the impact of two independent variables viz sodium alginate [A] and HPMC K4M [B] on the responses, such as floating lag time, percentage (%) water uptake at 2 h, and % drug release at 6 h and 12 h. Among various SDs prepared using PEG 6000, formulation 1:3 showed the highest drug solubility. FT-IR spectra revealed no interactions between the drug and the polymer. The percentage of drug content in NTB SDs ranged from 96.22 ± 1.67% to 97.70 ± 1.89%. The developed in situ gel formulations exhibited a pH value of approximately 7. An in vitro gelation study of the in situ gel formulation showed immediate gelation and was retained for a longer period. From the obtained results of 32 factorial designs, it was observed that all the selected factors had a significant effect on the chosen response, supporting the precision of design employed for optimization. Thus, the developed oral raft-forming in situ gelling system of NTB can be a promising and alternate approach to enhance retention in the stomach and to attain sustained release of drug by floating, thereby augmenting the therapeutic efficacy of NTB.

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“…The unique advantages of liposomes include minimal immune reactivity, reduced proteolytic degradation, increased circulation times and reproducible assembly in a cost-effective manner. As a result, liposomes are almost magical nanocarrier tools for diagnosis, monitoring and management of human disease 12 , 13 .…”

Section: Introductionmentioning

confidence: 99%

PEG2000-DBCO surface coating increases intracellular uptake of liposomes by breast cancer xenografts

Liu

Cohen

Turkman

2022

Sci Rep

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Given our interest in the utility of liposomes for molecular imaging and theranostics, we investigated how coating the outer layer of the liposome affects internalization by breast cancer cell lines in vitro and in breast tumor tissues in vivo. Indeed, we discovered that a remarkably high liposomal uptake can be achieved by DBCO (dibenzocyclooctyne) soft coating. Our data demonstrates that decorating the terminal lipid with a DBCO moiety at a specific density induces increased tumor uptake in vivo (tumor uptake ~ 50%) compared to conventional undecorated liposome (tumor uptake ~ 20%). In this study, we report improved visualization of breast cancer cells in vivo using a 4T1 orthotopic breast cancer model and primary breast tumor xenograft models MDA-MB-231 and MDA-MB-436. L-PEG2000-DBCO coated liposomes demonstrate increased accumulation in breast cancer cells independent of tumor size, type, position, receptor expression, as well as the condition of the host mice. We expect these findings to have a major positive impact on the practical utility of liposomes in image-guided applications and precision medicine theranostics.

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Smart Nanocarriers as an Emerging Platform for Cancer Therapy: A Review

Cited by 77 publications

References 201 publications

Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies

Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies

Development and Characterization of Oral Raft Forming In Situ Gelling System of Neratinib Anticancer Drug Using 32 Factorial Design

PEG2000-DBCO surface coating increases intracellular uptake of liposomes by breast cancer xenografts

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