Organic Nanoparticles as Drug Delivery Systems and Their Potential Role in the Treatment of Chronic Myeloid Leukemia

Kamareddine, Mohammed Hussein; Ghosn, Youssef; Tawk, Antonios; Elia, Carlos; Alam, Walid; Makdessi, Joseph; Farhat, Said

doi:10.1177/1533033819879902

Cited by 31 publications

(16 citation statements)

References 122 publications

(172 reference statements)

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“…For example, chronic myeloid leukemia (CML) can still only be clinically healed but not cured, with 40 % of patients free of treatment after therapy [ 11 – 13 ]. Polymeric nanocarriers could be a promising strategy to interact more efficiently with immune cells and enhance the intracellular concentration of active agents to counteract mechanisms such as drug resistance or poor response to treatment [ 14 , 15 ]. In this regard, the group of E. Wagner could already show successful transfection of pDNA with poly(ethylene imine) (PEI) only in combination with transferrin [ 16 – 18 ].…”

Section: Introductionmentioning

confidence: 99%

Improved gene delivery to K-562 leukemia cells by lipoic acid modified block copolymer micelles

et al. 2021

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Although there has been substantial progress in the research field of gene delivery, there are some challenges remaining, e.g. there are still cell types such as primary cells and suspension cells (immune cells) known to be difficult to transfect. Cationic polymers have gained increasing attention due to their ability to bind, condense and mask genetic material, being amenable to scale up and highly variable in their composition. In addition, they can be combined with further monomers exhibiting desired biological and chemical properties, such as antioxidative, pH- and redox-responsive or biocompatible features. By introduction of hydrophobic monomers, in particular as block copolymers, cationic micelles can be formed possessing an improved chance of transfection in otherwise challenging cells. In this study, the antioxidant biomolecule lipoic acid, which can also be used as crosslinker, was incorporated into the hydrophobic block of a diblock copolymer, poly{[2-(dimethylamino)ethyl methacrylate]101-b-[n-(butyl methacrylate)124-co-(lipoic acid methacrylate)22]} (P(DMAEMA101-b-[nBMA124-co-LAMA22])), synthesized by RAFT polymerization and assembled into micelles (LAMA-mic). These micelles were investigated regarding their pDNA binding, cytotoxicity mechanisms and transfection efficiency in K-562 and HEK293T cells, the former representing a difficult to transfect, suspension leukemia cell line. The LAMA-mic exhibited low cytotoxicity at applied concentrations but demonstrated superior transfection efficiency in HEK293T and especially K-562 cells. In-depth studies on the transfection mechanism revealed that transfection efficiency in K-562 cells does not depend on the specific oncogenic fusion gene BCR-ABL alone. It is independent of the cellular uptake of polymer-pDNA complexes but correlates with the endosomal escape of the LAMA-mic. A comparison of the transfection efficiency of the LAMA-mic with structurally comparable micelles without lipoic acid showed that lipoic acid is not solely responsible for the superior transfection efficiency of the LAMA-mic. More likely, a synergistic effect of the antioxidative lipoic acid and the micellar architecture was identified. Therefore, the incorporation of lipoic acid into the core of hydrophobic-cationic micelles represents a promising tailor-made transfer strategy, which can potentially be beneficial for other difficult to transfect cell types.

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Section: Introductionmentioning

confidence: 99%

Improved gene delivery to K-562 leukemia cells by lipoic acid modified block copolymer micelles

et al. 2021

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“…The administration of a DDSs in in vivo cancer models has been used in intravenous, intra-tumor, and localized manner (Patra et al, 2018;Sharma, 2019). These strategies are based on organic, inorganic, and polymeric materials (Kamareddine et al, 2019). The organic NCs are composed by phospholipids, carbohydrates, and nucleic acids, forming, e.g., micelles and liposomes, which can encapsulate drugs or activate molecules depending on their charge or their hydrophobic or hydrophilic behavior (López-Dávila et al, 2012).…”

Section: Drug Delivery Systemsmentioning

confidence: 99%

Smart Drug Delivery Strategies for Cancer Therapy

Mendoza

Alcántara-Quintana

2022

Front. Nanotechnol.

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Chemotherapy is one of the most widely used strategies to fight cancer, although it has disadvantages such as accumulation in healthy organs and lack of specificity by cancer cells (non-targeted molecules), among others, resulting in adverse effects on patients that limit the dose or follow-up with the same. However, the treatment can also fail due to the resistance mechanisms that cancer cells have to these agents. Because of these limitations, smart drug delivery strategies have been developed to overcome treatment challenges. These smart drug strategies are made with the aim of passively or actively releasing the drug into the tumor environment, increasing the uptake of the chemotherapeutic agent by the cancer cells, thus reducing the adverse effects on other vital organs. Also, these strategies can be guided with molecules on their surface that interact with the tumor microenvironment or with specific receptors on the cancer cell membrane, thus conferring high affinity. This mini review summarizes advances in the development of drug delivery techniques for cancer treatment, including different smart nanocarriers with single or multifunctional stimuli responsiveness. At the same time, we highlight the toxicity and delivery of these strategies in in vivo models. Despite innovation in smart delivery techniques, there are still biodistribution and customization challenges to be overcome in future research.

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Section: Nanoparticles As Elements Of Therapy For Malignant Gliomamentioning

confidence: 99%

“…Organic nanoparticles display highly desirable characteristics in the biomedical field ( Hussein Kamareddine et al, 2019 ). They have a dynamic nature and are able to respond to environmental variations in temperature, pH, and UV radiation ( Jagannathan et al, 2006 ; Affram et al, 2017 ; Hussein Kamareddine et al, 2019 ). Furthermore, they can easily cross biological barriers and are considered less toxic due to its biodegradability; therefore, they are ideal as drug or gene delivery systems ( Jagannathan et al, 2006 ; Hussein Kamareddine et al, 2019 ).…”

Section: Nanoparticles As Elements Of Therapy For Malignant Gliomamentioning

confidence: 99%

“…They have a dynamic nature and are able to respond to environmental variations in temperature, pH, and UV radiation ( Jagannathan et al, 2006 ; Affram et al, 2017 ; Hussein Kamareddine et al, 2019 ). Furthermore, they can easily cross biological barriers and are considered less toxic due to its biodegradability; therefore, they are ideal as drug or gene delivery systems ( Jagannathan et al, 2006 ; Hussein Kamareddine et al, 2019 ). Liposomes, vesicles, micelles, polymeric NPs, and dendrimers are all among the most common organic nanoparticles (for specific characteristic and applications, see Figure 1 ); however, among all of them, polymeric NPs are probably the most relevant in cancer research.…”

Section: Nanoparticles As Elements Of Therapy For Malignant Gliomamentioning

confidence: 99%

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Nanoparticles for Stem Cell Therapy Bioengineering in Glioma

Ruiz‐Garcia

Alvarado-Estrada

Krishnan

et al. 2020

Front. Bioeng. Biotechnol.

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Gliomas are a dismal disease associated with poor survival and high morbidity. Current standard treatments have reached a therapeutic plateau even after combining maximal safe resection, radiation, and chemotherapy. In this setting, stem cells (SCs) have risen as a promising therapeutic armamentarium, given their intrinsic tumor homing as well as their natural or bioengineered antitumor properties. The interplay between stem cells and other therapeutic approaches such as nanoparticles holds the potential to synergize the advantages from the combined therapeutic strategies. Nanoparticles represent a broad spectrum of synthetic and natural biomaterials that have been proven effective in expanding diagnostic and therapeutic efforts, either used alone or in combination with immune, genetic, or cellular therapies. Stem cells have been bioengineered using these biomaterials to enhance their natural properties as well as to act as their vehicle when anticancer nanoparticles need to be delivered into the tumor microenvironment in a very precise manner. Here, we describe the recent developments of this new paradigm in the treatment of malignant gliomas.

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Organic Nanoparticles as Drug Delivery Systems and Their Potential Role in the Treatment of Chronic Myeloid Leukemia

Cited by 31 publications

References 122 publications

Improved gene delivery to K-562 leukemia cells by lipoic acid modified block copolymer micelles

Improved gene delivery to K-562 leukemia cells by lipoic acid modified block copolymer micelles

Smart Drug Delivery Strategies for Cancer Therapy

Nanoparticles for Stem Cell Therapy Bioengineering in Glioma

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