A highly potent maytansinoid analogue and its use as a cytotoxic therapeutic agent in gold nanoparticles for the treatment of hepatocellular carcinoma

Porter, John; Ding, Yao; Hale, Sarah; Perrins, Richard D.; Robinson, Angela Byun; Mazanetz, Michael P.; Wu, Yubo; Ma, Yinping; Conlon, Kelly; Coulter, Tom

doi:10.1016/j.bmcl.2020.127634

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…[ 15 , 16 ] The acylation reaction of maytansinol is a crucial step in the preparation of maytansinoid ADCs or nanoparticles, constituting an uprising class of targeted cancer therapeutics. [ 17 , 18 , 19 , 20 , 21 ] A few attempts to conjugate maytansinoids to peptides by this reaction have also been made very recently. [ 22 , 23 ] Furthermore, considering that the maytansine binding site is one of the most recently identified and least explored on tubulin, acylation of maytansinol may serve for the preparation of useful molecular probes to better understand the structure‐activity relationships of maytansinoids or to identify new maytansine‐site ligands.…”

Section: Introductionmentioning

confidence: 99%

Maytansinol Derivatives: Side Reactions as a Chance for New Tubulin Binders

Marzullo

Boiarska

Pérez‐Peña

et al. 2021

Chemistry A European J

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Maytansinol is a valuable precursor for the preparation of maytansine derivatives (known as maytansinoids). Inspired by the intriguing structure of the macrocycle and the success in targeted cancer therapy of the derivatives, we explored the maytansinol acylation reaction. As a result, we were able to obtain a series of derivatives with novel modifications of the maytansine scaffold. We characterized these molecules by docking studies, by a comprehensive biochemical evaluation, and by determination of their crystal structures in complex with tubulin. The results shed further light on the intriguing chemical behavior of maytansinoids and confirm the relevance of this peculiar scaffold in the scenario of tubulin binders.

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Section: Introductionmentioning

confidence: 99%

Maytansinol Derivatives: Side Reactions as a Chance for New Tubulin Binders

Marzullo

Boiarska

Pérez‐Peña

et al. 2021

Chemistry A European J

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“…[1][2][3] Their highly efficient mechanism of capping MT-dynamics [4] has led to their successful application in cancer treatment as antibody-drug conjugates (ADCs). [5][6][7] This success has further prompted their development as targeted cancer therapeutics, for example, in the form of nanoparticles [8,9] or recently reported immune checkpoint-targeting maytansinoid conjugates. [10] However, the high-affinity of maytansine towards β-tubulin (K D = 6.8-14 nM) not only makes it well suited as a cytotoxin, but also derivatives with a similar affinity could be used as molecular probes.…”

Section: Introductionmentioning

confidence: 99%

Maytansinol Functionalization: Towards Useful Probes for Studying Microtubule Dynamics

Boiarska

Pérez‐Peña

Abbel

et al. 2022

Chemistry A European J

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Maytansinoids are a successful class of natural and semisynthetic tubulin binders, known for their potent cytotoxic activity. Their wider application as cytotoxins and chemical probes to study tubulin dynamics has been held back by the complexity of natural product chemistry. Here we report the synthesis of long-chain derivatives and maytansinoid conjugates. We confirmed that bulky substituents do not impact their high activity or the scaffold's binding mode.These encouraging results open new avenues for the design of new maytansine-based probes.

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“…Polymeric micelles as nanoscale vehicles have been extensively studied for drug delivery, which offers remarkable advantages over the free drugs administration, such as higher solubility, longer circulation time in the biological systems, and improved tumor uptake via active or passive mechanisms. [26][27][28][29][30][31][32] A novel multifunctional platform for simultaneous photothermal therapy and chemotherapy was developed by incorporating Au nanoparticles into the drugloaded micelles. Upon NIR irradiation, cytotoxic heat is locally generated due to NIR resonance of Au nanoparticles, and the elevated temperature would accelerate the drug release from the micelles, resulting in the synergetic therapy effect.…”

Section: Introductionmentioning

confidence: 99%

AuNPs Decorated PLA Stereocomplex Micelles for Synergetic Photothermal and Chemotherapy

Fan

Luo

et al. 2021

Macromolecular Bioscience

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A unique platform for combined photothermal and chemotherapy using PLA stereocomplex (PLA SC) micelles-induced hybrid gold nanocarriers is designed. The PLA SC micelles, made from the self-assembly of poly(ethylene glycol)-block-poly(l-lactide) (PEG-PLLA) and poly(2-(dimethylamino) ethyl methacrylate)-block-poly(d-lactide) (PDMAEMA-PDLA), for the first time are used as a template to fabricate the hybrid PLA SC@Au core-shell nanocarriers, in which the anticancer drugs are encapsulated within the core, while the Au nanoparticles are tethered in the shell via the in situ reduction of AuCl 4 − by PDMAEMA. The obtained PLA SC@Au hybrid nanocarriers exhibit low toxicity and remarkable photothermal effect. Upon near-infrared laser irradiation, the on-site photothermal therapy can further induce an accelerated drug release from the hybrid nanocarrier reservoir via hyperthermia heating of the nanocarriers, thus leading to a synergistic photothermal and chemotherapy toward a significantly improved efficacy in tumor shrinkage. The as-designed PLA SC@Au hybrid nanocarriers, with their biocompatible compositions, dual-drug delivery characteristics, and combined photothermal/chemotherapy, show high potential as a novel platform for cancer treatment.

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A highly potent maytansinoid analogue and its use as a cytotoxic therapeutic agent in gold nanoparticles for the treatment of hepatocellular carcinoma

Cited by 5 publications

References 32 publications

Maytansinol Derivatives: Side Reactions as a Chance for New Tubulin Binders

Maytansinol Derivatives: Side Reactions as a Chance for New Tubulin Binders

Maytansinol Functionalization: Towards Useful Probes for Studying Microtubule Dynamics

AuNPs Decorated PLA Stereocomplex Micelles for Synergetic Photothermal and Chemotherapy

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