A multifunctional drug nanocarrier for efficient anticancer therapy

Teijeiro-Valiño, Carmen; Novoa-Carballal, Ramón; Borrajo, Erea; Vidal, Anxo; Alonso-Nocelo, Marta; Fuente, María de la; López-Casas, Pedro P.; Hidalgo, Manuel; Csaba, Nœmi; Alonso, María José

doi:10.1016/j.jconrel.2018.12.002

Cited by 31 publications

(32 citation statements)

References 55 publications

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“…This fact con rms that the biological function of the hormone remains intact despite the chemical modi cation. Although many reports in the literature have shown diverse ways to conjugate ligands to the nanosystems surface, the majority of them do not specify the ligand density obtained [30,44,[48][49][50]. The values of ligand density observed in this work are in line with those reported for different nanosystems, oscillating from 0.225 to 0.005 molecules/nm 2 [30,44].…”

Section: Discussionsupporting

confidence: 81%

“…Nanosystems intended for cancer treatment have been mostly designed relying on the intrinsic capacity of these small particles to enhance their circulation times and eventually undergo passive accumulation into the tumor tissues due to the enhanced permeability and retention effect (EPR effect) [29]. Recent studies highlighted the need for targeted therapies that could enhance the accumulation of nanoparticles in the tumor [30,31]. By means of active targeting, nanoparticles can theoretically achieve higher levels of drug concentration in tumour tissues via receptor-mediated endocytosis [17].…”

Section: Discussionmentioning

confidence: 99%

“…Although many reports in the literature have shown diverse ways to conjugate ligands to the nanosystems surface, the majority of them do not specify the ligand density obtained [30,44,[48][49][50]. The values of ligand density observed in this work are in line with those reported for different nanosystems, oscillating from 0.225 to 0.005 molecules/nm 2 [30,44]. The use of combination therapies involving the incorporation of two anticancer agents into a nanosystem may provide bene ts in the sense that different drugs may attack cancer cells at varying stages of their growth cycle [51].…”

Section: Discussionmentioning

confidence: 99%

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Uroguanylin-decorated Nanosystems Containing Etoposide, a Potential Targeted Combination Therapy for Colorectal Cancer

Bouzo

Lores

Jatal

et al. 2020

Preprint

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Colorectal cancer is the third most frequently diagnosed cancer malignancy and the second leading cause of cancer-related deaths worldwide. Guanylyl Cyclase C (GCC), a membrane receptor that is expressed in 95% of primary and metastatic colorectal cancer tumors is a promising target for the design of new drug delivery strategies. In this work we propose the use of Uroguanylin (UroG), a natural ligand for GCC, for the preparation of targeted sphingomyelin-based nanosystems (UroG-SNs). The results from in vitro cell culture studies showed that UroG-SNs have a specific interaction with the GCC receptor, resulting in an antiproliferative response. Subsequently, the anti-cancer drug etoposide (Etp) was encapsulated into the UroG-SNs. The evaluation of the resulting system showed a synergistic effect of the two drugs, thus highlighting the therapeutic potential of this strategy for the treatment of colorectal cancer.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Uroguanylin-decorated Nanosystems Containing Etoposide, a Potential Targeted Combination Therapy for Colorectal Cancer

Bouzo

Lores

Jatal

et al. 2020

Preprint

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“…At the same time, the formulation of polynucleotides within nanosystems is able to protect them from degradation (45). Bearing all this in mind, we have formulated poly(I:C) in the form of nanocomplexes enveloped with two biodegradable and stabilizing polymers (PEG-PGA and HA), known to facilitate the arrival to the tumor site (40,(46)(47)(48)(49)(50)(51)(52)(53). Once in the tumor, a preferential uptake of the nanosystems by macrophages could be anticipated due to their high phagocytic capacity, as already described for both, targeted and non-targeted nanosystems (15,54,55).…”

Section: Design and Development Of Poly(i:c) Nanocomplexesmentioning

confidence: 99%

Arginine-Based Poly(I:C)-Loaded Nanocomplexes for the Polarization of Macrophages Toward M1-Antitumoral Effectors

et al. 2020

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Tumor-associated macrophages (TAMs), with M2-like immunosuppressive profiles, are key players in the development and dissemination of tumors. Hence, the induction of M1 pro-inflammatory and anti-tumoral states is critical to fight against cancer cells. The activation of the endosomal toll-like receptor 3 by its agonist poly(I:C) has shown to efficiently drive this polarization process. Unfortunately, poly(I:C) presents significant systemic toxicity, and its clinical use is restricted to a local administration. Therefore, the objective of this work has been to facilitate the delivery of poly(I:C) to macrophages through the use of nanotechnology, that will ultimately drive their phenotype toward pro-inflammatory states. Methods: Poly(I:C) was complexed to arginine-rich polypeptides, and then further enveloped with an anionic polymeric layer either by film hydration or incubation. Physicochemical characterization of the nanocomplexes was conducted by dynamic light scattering and transmission electron microscopy, and poly(I:C) association efficiency by gel electrophoresis. Primary human-derived macrophages were used as relevant in vitro cell model. Alamar Blue assay, ELISA, PCR and flow cytometry were used to determine macrophage viability, polarization, chemokine secretion and uptake of nanocomplexes. The cytotoxic activity of pre-treated macrophages against PANC-1 cancer cells was assessed by flow cytometry. Results: The final poly(I:C) nanocomplexes presented sizes lower than 200 nm, with surface charges ranging from +40 to −20 mV, depending on the envelopment. They all presented high poly(I:C) loading values, from 12 to 50%, and great stability in cell culture media. In vitro, poly(I:C) nanocomplexes were highly taken up by macrophages, in comparison to the free molecule. Macrophage treatment with these nanocomplexes did not reduce their viability and efficiently stimulated the secretion of the T-cell recruiter chemokines CXCL10 and CCL5, of great importance for an effective anti-tumor immune response. Finally, poly(I:C) nanocomplexes significantly increased the ability of treated macrophages to directly kill cancer cells. Dacoba et al. Poly(I:C) Nanocomplexes for Macrophage M1-Polarization Conclusion: Overall, these enveloped poly(I:C) nanocomplexes might represent a therapeutic option to fight cancer through the induction of cytotoxic M1-polarized macrophages.

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“…In vitro study showed these nanocapsules could interact with the NRP1 receptors over-expressed in cancer cells. The results showed a dramatic accumulation of DTX in the tumor and a reduction of the tumor [ 119 ]. Accordingly, a poly-L-lysine coated PTX loaded PLGA NPs formulation showed the inhibition of tumor growth and anti-metastasis against PC [ 122 ].…”

Section: Application and Clinical Trials Of Nanocarrier-based Thermentioning

confidence: 99%

Recent Progress of Nanocarrier-Based Therapy for Solid Malignancies

Wei

Lau

2020

Cancers

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Conventional chemotherapy is still an important option of cancer treatment, but it has poor cell selectivity, severe side effects, and drug resistance. Utilizing nanoparticles (NPs) to improve the therapeutic effect of chemotherapeutic drugs has been highlighted in recent years. Nanotechnology dramatically changed the face of oncology by high loading capacity, less toxicity, targeted delivery of drugs, increased uptake to target sites, and optimized pharmacokinetic patterns of traditional drugs. At present, research is being envisaged in the field of novel nano-pharmaceutical design, such as liposome, polymer NPs, bio-NPs, and inorganic NPs, so as to make chemotherapy effective and long-lasting. Till now, a number of studies have been conducted using a wide range of nanocarriers for the treatment of solid tumors including lung, breast, pancreas, brain, and liver. To provide a reference for the further application of chemodrug-loaded nanoformulations, this review gives an overview of the recent development of nanocarriers, and the updated status of their use in the treatment of several solid tumors.

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A multifunctional drug nanocarrier for efficient anticancer therapy

Cited by 31 publications

References 55 publications

Uroguanylin-decorated Nanosystems Containing Etoposide, a Potential Targeted Combination Therapy for Colorectal Cancer

Uroguanylin-decorated Nanosystems Containing Etoposide, a Potential Targeted Combination Therapy for Colorectal Cancer

Arginine-Based Poly(I:C)-Loaded Nanocomplexes for the Polarization of Macrophages Toward M1-Antitumoral Effectors

Recent Progress of Nanocarrier-Based Therapy for Solid Malignancies

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