Synthesis of micellar-like terpolymer nanoparticles with reductively-cleavable cross-links and evaluation of efficacy in 2D and 3D models of triple negative breast cancer

Monteiro, Patricia; Gulfam, Muhammad; Monteiro, Cíntia J.; Travanut, Alessandra; Abelha, Thais Fedatto; Pearce, Amanda K.; Jérôme, Christine; Grabowska, Anna; Clarke, Paula J.; Collins, Hilary M.; Heery, David M.; Gershkovich, Pavel; Alexander, Cameron

doi:10.1016/j.jconrel.2020.04.049

Cited by 16 publications

(22 citation statements)

References 58 publications

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“…GSH is a common internal environmental stimulus in cells that rapidly destroys the stability of intracellular nanocarriers to achieve effective drug release ( Cheng et al, 2011 ) ( Figure 4A ). Several researchers have focused on developing functional carriers with reduction responsiveness based on two strategies: insertion of disulfide bonds in the polymer backbone or using reduction-sensitive cross-linking molecules ( Gulfam et al, 2017 ; Conte et al, 2018 ; Deng et al, 2018 ; Monteiro et al, 2020 ). Glutathione (GSH) levels inside and outside cancer cells are markedly different ( Lai et al, 2021 ; Liu et al, 2021 ).…”

Section: Non-specific Targeted Therapeutic Nanocarriers For Treatment Of Bladder Cancermentioning

confidence: 99%

Functional Nanomedicines for Targeted Therapy of Bladder Cancer

et al. 2021

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Bladder cancer is one of most common malignant urinary tract tumor types with high incidence worldwide. In general, transurethral resection of non-muscle-invasive bladder cancer followed by intravesical instillation of chemotherapy is the standard treatment approach to minimize recurrence and delay progression of bladder cancer. However, conventional intravesical chemotherapy lacks selectivity for tumor tissues and the concentration of drug is reduced with the excretion of urine, leading to frequent administration and heavy local irritation symptoms. While nanomedicines can overcome all the above shortcomings and adhere to the surface of bladder tumors for a long time, and continuously and efficiently release drugs to bladder cancers. The rapid advances in targeted therapy have led to significant improvements in drug efficacy and precision of targeted drug delivery to eradicate tumor cells, with reduced side-effects. This review summarizes the different available nano-systems of targeted drug delivery to bladder cancer tissues. The challenges and prospects of targeted therapy for bladder cancer are additionally discussed.

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Section: Non-specific Targeted Therapeutic Nanocarriers For Treatment Of Bladder Cancermentioning

confidence: 99%

Functional Nanomedicines for Targeted Therapy of Bladder Cancer

et al. 2021

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“…Reduction‐responsive polymeric carriers with disulfide bonds have been studied by many research groups. These systems have been designed mainly using two different strategies: insertion of a disulfide bond on the polymer backbone chains or the use of reduction‐sensitive crosslink molecules which can be incorporated in the core or shell of the appropriate nanocarriers (Conte et al, 2018; Z. Deng, Yuan, Xu, Liang, & Liu, 2018; Gulfam et al, 2017; Guo et al, 2018; X. Q. Li et al, 2011; Monteiro et al, 2020; C. Shi et al, 2014). In the presence of high levels of reduced GSH in tumor cells, disulfide bonds can, in principle, be easily broken down into sulfhydryl groups which results in the disassembly of carriers and consequently in the release of cargoes (Chakravarthi, Jessop, & Bulleid, 2006).…”

Section: Design Of Reduction‐responsive Polymeric Carriersmentioning

confidence: 99%

“…Furthermore, the key finding in this article was that placement of the disulfide cross‐links in poly(caprolactone)‐co‐poly(lactide) regions of the “cores,” compared to in poly(caprolactone) only regions, enhanced the reactivity toward GSH. This demonstrated that access of GSH to the disulfide links varied, dependent on the nature of the polymer backbone carrying the disulfides, and suggests that it might be possible to tune the reduction response of delivery systems via specific placement of disulfides in bespoke regions of a polymer (Monteiro et al, 2020).…”

Section: Design Of Reduction‐responsive Polymeric Carriersmentioning

confidence: 99%

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Reduction‐responsive polymers for drug delivery in cancer therapy—Is there anything new to discover?

Monteiro

Travanut

Conte

et al. 2020

WIREs Nanomed Nanobiotechnol

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Among various types of stimuli‐responsive drug delivery systems, reduction‐responsive polymers have attracted great interest. In general, these systems have high stability in systemic circulation, however, they can respond quickly to differences in the concentrations of reducing species in specific physiological sites associated with a pathology. This is a particularly relevant strategy to target diseases in which hypoxic regions are present, as polymers which are sensitive to in‐situ expressed antioxidant species can, through a local response, release a therapeutic at high concentration in the targeted site, and thus, improve the selectivity and efficacy of the treatment. At the same time, such reduction‐responsive materials can also decrease the toxicity and side effects of certain drugs. To date, polymers containing disulfide linkages are the most investigated of the class of reduction‐responsive nanocarriers, however, other groups such as selenide and diselenide have also been used for the same purpose. In this review article, we discussed the rationale behind the development of reduction‐responsive polymers as drug delivery systems and highlight examples of recent progress. We include the most popular design methods to generate reduction‐responsive polymeric carriers and their applications in cancer therapy, and question what areas may still need to be explored in a field with already a very large number of research articles. Finally, we consider the main challenges associated with the clinical translation of these nanocarriers and the future perspectives in this area. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies

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“…Therefore, the toxicity of P1 was further investigated by performing Annexin‐V/PI assays, which were used to discriminate between viable, apoptotic and dead cells using flow cytometry. [ 17 ] MDA‐MB‐231 cells were incubated with P1 polymersomes at 100 µg mL −1 and 500 µg mL −1 in media for 48 h. At the lower concentration (100 µg mL −1 ) P1 was less toxic as measured by the percentage of live cells (96.18% ± 0.29) compared to the number of live cells when P1 at 500 µg mL −1 was used (94.34% ± 0.65). These data indicated that, for this assay at least, P1 caused only a small reduction in cell viability as deduced from protease activity.…”

Section: Figurementioning

confidence: 99%

Synthesis of Passerini‐3CR Polymers and Assembly into Cytocompatible Polymersomes

Travanut

Monteiro

Oelmann

et al. 2020

Macromol. Rapid Commun.

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The versatility of the Passerini three component reaction (Passerini‐3CR) is herein exploited for the synthesis of an amphiphilic diblock copolymer, which self‐assembles into polymersomes. Carboxy‐functionalized poly(ethylene glycol) methyl ether is reacted with AB‐type bifunctional monomers and tert‐butyl isocyanide in a single process via Passerini‐3CR. The resultant diblock copolymer (P1) is obtained in good yield and molar mass dispersity and is well tolerated in model cell lines. The Passerini‐3CR versatility and reproducibility are shown by the synthesis of P2, P3, and P4 copolymers. The ability of the Passerini P1 polymersomes to incorporate hydrophilic molecules is verified by loading doxorubicin hydrochloride in P1DOX polymersomes. The flexibility of the synthesis is further demonstrated by simple post‐functionalization with a dye, Cyanine‐5 (Cy5). The obtained P1‐Cy5 polymersomes rapidly internalize in 2D cell monolayers and penetrate deep into 3D spheroids of MDA‐MB‐231 triple‐negative breast cancer cells. P1‐Cy5 polymersomes injected systemically in healthy mice are well tolerated and no visible adverse effects are seen under the conditions tested. These data demonstrate that new, biodegradable, biocompatible polymersomes having properties suitable for future use in drug delivery can be easily synthesized by the Passerini‐3CR.

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Synthesis of micellar-like terpolymer nanoparticles with reductively-cleavable cross-links and evaluation of efficacy in 2D and 3D models of triple negative breast cancer

Cited by 16 publications

References 58 publications

Functional Nanomedicines for Targeted Therapy of Bladder Cancer

Functional Nanomedicines for Targeted Therapy of Bladder Cancer

Reduction‐responsive polymers for drug delivery in cancer therapy—Is there anything new to discover?

Synthesis of Passerini‐3CR Polymers and Assembly into Cytocompatible Polymersomes

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