Polymer design and component selection contribute to uptake, distribution &amp; trafficking behaviours of polyethylene glycol hyperbranched polymers in live MDA-MB-468 breast cancer cells

Simpson, Joshua D.; Ediriweera, Gayathri R.; Howard, Christopher B.; Fletcher, Nicholas L.; Bell, Craig A.; Thurecht, Kristofer J.

doi:10.1039/c9bm00957d

Cited by 13 publications

(39 citation statements)

References 51 publications

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“…Its magnetic core makes it possible for utilization in the diagnosis as it is detected by MRI on injection to tissues. On one side, where Poly-L-glutamic acid (PLGA; a synthetic biodegradable polymer) is employed for conjugate synthesis, polyethylene glycol (PEG) and N-(2-hydroxypropyl)-methacryl amide copolymer (HPMA) are the most widely used non-biodegradable polymers of synthetic origin [40][41][42][43]. PLGA (Poly-(lactic-co-glycolic acid) nanoencapsulated with Callistemon citrinus phenolics exhibited anticancer properties against BC cell lines viz.…”

Section: Polymeric-based Nanoparticlesmentioning

confidence: 99%

Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPRER) and Beyond

Rahman

Kumar

et al. 2021

Biomedicines

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Breast cancer (BC) is the second most frequent cause of death among women. Representing a complex and heterogeneous type of cancer, its occurrence is attributed by both genetic (gene mutations, e.g., BRCA1, BRCA2) and non-genetic (race, ethnicity, etc.) risk factors. The effectiveness of available treatment regimens (small molecules, cytotoxic agents, and inhibitors) decreased due to their poor penetration across biological barriers, limited targeting, and rapid body clearance along with their effect on normal resident cells of bone marrow, gastrointestinal tract, and hair follicles. This significantly reduced their clinical outcomes, which led to an unprecedented increase in the number of cases worldwide. Nanomedicine, a nano-formulation of therapeutics, emerged as a versatile delivering module for employment in achieving the effective and target specific delivery of pharmaceutical payloads. Adoption of nanotechnological approaches in delivering therapeutic molecules to target cells ensures not only reduced immune response and toxicity, but increases the stability of therapeutic entities in the systemic circulation that averts their degradation and as such increased extravasations and accumulation via enhanced permeation and the retention (EPR) effect in target tissues. Additionally, nanoparticle (NP)-induced ER stress, which enhances apoptosis and autophagy, has been utilized as a combative strategy in the treatment of cancerous cells. As nanoparticles-based avenues have been capitalized to achieve better efficacy of the new genera of therapeutics with enhanced specificity and safety, the present study is aimed at providing the fundamentals of BC, nanotechnological modules (organic, inorganic, and hybrid) employed in delivering different therapeutic molecules, and mechanistic insights of nano-ER stress induced apoptosis and autophagy with a perspective of exploring this avenue for use in the nano-toxicological studies. Furthermore, the current scenario of USA FDA approved nano-formulations and the future perspective of nanotechnological based interventions to overcome the existing challenges are also discussed.

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Section: Polymeric-based Nanoparticlesmentioning

confidence: 99%

Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPRER) and Beyond

Rahman

Kumar

et al. 2021

Biomedicines

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“…On the other hand, if designed carefully, this interaction can also be exploited, for example, for the accumulation in specific cell organelles. [74,75] Furthermore, such polymeric nano-theranostics allow for real-time monitoring of nanomedicine interventions, enhancing personalized medicine approaches, and providing clinicians otherwise unavailable information for predicting patient outcomes at the earliest possible time. Such combination approaches afforded by nanomedicines are at the forefront of next-generation nanomedicines being developed, and the authors expect these to have a significant impact in future clinical outcomes, especially in difficult-to-treat malignancies with currently poor clinical outcomes.…”

Section: Theranostics-combining Therapeutics and Diagnosticsmentioning

confidence: 99%

“…On the other hand, if designed carefully, this interaction can also be exploited, for example, for the accumulation in specific cell organelles. [ 74,75 ]…”

Section: Theranostics—combining Therapeutics and Diagnosticsmentioning

confidence: 99%

Next‐Generation Polymeric Nanomedicines for Oncology: Perspectives and Future Directions

Fletcher

Kempe

Thurecht

2020

Macromol. Rapid Commun.

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Precision polymers as advanced nanomedicines represent an appealing approach for the treatment of otherwise untreatable malignancies. By taking advantage of unique nanomaterial properties and implementing judicious design strategies, polymeric nanomedicines are able to be produced that overcome many barriers to effective treatment. Current key research focus areas anticipated to produce the greatest impact in polymer applications in nanomedicine for oncology include new strategies to achieve “active” targeting, polymeric pro‐drug activation, and combinatorial polymer drug delivery approaches in combination with enhanced understanding of complex bio‐nano interactions. These approaches, both in isolation or combination, form the next generation of precision nanomedicines with significant anticipated future health outcomes. Of necessity, these approaches will combine an intimate understanding of biological interactions with advanced materials design. This perspectives piece aims to highlight emerging opportunities that promise to be game changers in the nanomedicine oncology field. Discussed herein are current and next generation polymeric nanomedicines with a focus towards structures that are, or could, undergo clinical translation as well as highlight key advances in the field.

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“…58 Or, appending biologically relevant groups on SHP linear segments can endow the SHP with significant therapeutic potential. In this regard, the Thurecht group has pioneered an impressive range of potential applications for biologically relevant SHPs, 50,51,[59][60][61][62][63][64][65][66][67][68][69][70][71][72] including fluorine-labeled SHPs for 19 F magnetic resonance imaging, 63,67,73 hyperpolarized SHPs that could enhance traditional magnetic resonance imaging 72 and SHP delivery vehicles for peptides and nucleic acids. 51,59,60,69 Appel and coworkers also very recently demonstrated that targeting low primary chain degrees of polymerization enables extensive decoration of SHPs with functional chain ends.…”

Section: Synthesis Of Functional Shpsmentioning

confidence: 99%

Controlled radical copolymerization of multivinyl crosslinkers: a robust route to functional branched macromolecules

Sims

2020

Polymer International

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Controlled radical polymerization (CRP) has both revolutionized the synthesis of linear polymers and enabled unprecedented topological complexity. While the synthesis of many polymeric architectures requires careful planning and specialized precursors, branched macromolecules such as segmented hyperbranched polymers (SHPs), knotted polymers, core-crosslinked stars (CCSs), and more can be synthesized through the copolymerization of vinyl monomers and divinyl crosslinkers in only a few steps. In the nearly two decades since its discovery, this strategy has helped elucidate the fundamental polymerization behavior of crosslinkers and also yielded a variety of functional and stimuli-responsive materials. The purpose of this mini-review is to therefore overview critical fundamental aspects of CRP of crosslinkers and materials derived therefrom. The process by which both SHPs and CCS polymers are synthesized, the effect of key reaction parameters and intriguing recent advances are described with the intent of both educating new researchers and inspiring new directions in this area.

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Polymer design and component selection contribute to uptake, distribution & trafficking behaviours of polyethylene glycol hyperbranched polymers in live MDA-MB-468 breast cancer cells

Abstract: Properties of hyperbranched polymer surface chemistry control cellular distribution.

Cited by 13 publications

References 51 publications

Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPRER) and Beyond

Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPRER) and Beyond

Next‐Generation Polymeric Nanomedicines for Oncology: Perspectives and Future Directions

Controlled radical copolymerization of multivinyl crosslinkers: a robust route to functional branched macromolecules

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