Polymer–drug conjugate therapeutics: advances, insights and prospects

Ekladious, Iriny; Colson, Yolonda L.; Grinstaff, Mark W.

doi:10.1038/s41573-018-0005-0

Cited by 654 publications

(459 citation statements)

References 281 publications

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“…Synthetic polymers with different architectures, such as linear, star, branched, and dendritic shapes as well as supramolecular assemblies, have been employed for tumor specific diagnosis and therapy . Several formulations have received market approval . For example, hydrophobic anticancer drugs are conjugated to the poly[ N ‐(2‐hydroxypropyl) methacrylamide] (pHPMA) via a stimuli‐sensitive linker because pHPMA is nontoxic, nonimmunogenic, and nonbiodegradable during circulation .…”

Section: Introductionmentioning

confidence: 99%

A Nanostrategy for Efficient Imaging‐Guided Antitumor Therapy through a Stimuli‐Responsive Branched Polymeric Prodrug

Cai¹,

Dai

Wang³

et al. 2020

Advanced Science

176

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A stimuli‐responsive polymeric prodrug‐based nanotheranostic system with imaging agents (cyanine5.5 and gadolinium‐chelates) and a therapeutic agent paclitaxel (PTX) is prepared via polymerization and conjugating chemistry. The branched polymeric PTX‐Gd‐based nanoparticles (BP‐PTX‐Gd NPs) demonstrate excellent biocompatibility, and high stability under physiological conditions, but they stimuli‐responsively degrade and release PTX rapidly in a tumor microenvironment. The in vitro behavior of NPs labeled with fluorescent dyes is effectively monitored, and the NPs display high cytotoxicity to 4T1 cells similar to free PTX by impairing the function of microtubules, downregulating anti‐apoptotic protein Bcl‐2, and upregulating the expression of Bax, cleaved caspase‐3, cleaved caspase‐9, cleaved‐PARP, and p53 proteins. Great improvement in magnetic resonance imaging (MRI) is demonstrated by these NPs, and MRI accurately maps the temporal change profile of the tumor volume after injection of NPs and the tumor treatment process is also closely correlated with the T1 values measured from MRI, demonstrating the capability of providing real‐time feedback to the chemotherapeutic treatment effectiveness. The imaging‐guided chemotherapy to the 4T1 tumor in the mice model achieves an excellent anti‐tumor effect. This stimuli‐responsive polymeric nano‐agent opens a new door for efficient breast cancer treatment under the guidance of fluorescence/MRI.

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Section: Introductionmentioning

confidence: 99%

A Nanostrategy for Efficient Imaging‐Guided Antitumor Therapy through a Stimuli‐Responsive Branched Polymeric Prodrug

Cai¹,

Dai

Wang³

et al. 2020

Advanced Science

176

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“…Microenvironment-triggered release plays an important role in controlling the location and concentration of therapeutic drugs in tumor therapy [1][2][3][4][5]. It can be induced by either tumor internal microenvironment or external forces [6], such as pH [7,8], overexpressed enzyme [9,10], high concentration of glutathione, temperature [11], microwave [12], and light [13,14], among others.…”

Section: Introductionmentioning

confidence: 99%

Manganese-Zeolitic Imidazolate Frameworks-90 with High Blood Circulation Stability for MRI-Guided Tumor Therapy

et al. 2019

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HIGHLIGHTS • Manganese-zeolitic imidazolate frameworks (Mn-ZIF-90) with both high drug loading and magnetic resonance imaging (MRI) in vitro and in vivo were prepared. • The modification of a newly designed pH-protective and active-targeting Y 1 receptor ligand reduces the drug release during blood circulation and specifically targets the tumor sites, improving therapeutic efficacy in vivo. • The combination of nano-size Mn-ZIF-90 and the highly specific Y 1 receptor ligand promotes the specific drug accumulation in tumor sites.

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“…Macromolecular and supramolecular tools of nanomedicine are academically successful in their own right and present a wide landscape of opportunities for drug delivery by EPR. Of these, PEGylation is arguably the most successful synthetic methodology to produce macromolecular (pro)drugs with optimized pharmacokinetics for both biological and small‐molecule therapeutics.…”

Section: Methodsmentioning

confidence: 99%

Molecular, Macromolecular, and Supramolecular Glucuronide Prodrugs: Lead Identified for Anticancer Prodrug Monotherapy

et al. 2020

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In this work, a tumor growth intervention by localized drug synthesis within the tumor volume, using the enzymatic repertoire of the tumor itself, is presented. Towards the overall success, molecular, macromolecular, and supramolecular glucuronide prodrugs were designed for a highly potent toxin, monomethyl auristatin E (MMAE). The lead candidate exhibited a fold difference in toxicity between the prodrug and the drug of 175, had an engineered mechanism to enhance the deliverable payload to tumours, and contained a highly potent toxin such that bioconversion of only a few prodrug molecules created a concentration of MMAE sufficient enough for efficient suppression of tumor growth. Each of these points is highly significant and together afford a safe, selective anticancer measure, making tumor‐targeted glucuronides attractive for translational medicine.

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Polymer–drug conjugate therapeutics: advances, insights and prospects

Cited by 654 publications

References 281 publications

A Nanostrategy for Efficient Imaging‐Guided Antitumor Therapy through a Stimuli‐Responsive Branched Polymeric Prodrug

A Nanostrategy for Efficient Imaging‐Guided Antitumor Therapy through a Stimuli‐Responsive Branched Polymeric Prodrug

Manganese-Zeolitic Imidazolate Frameworks-90 with High Blood Circulation Stability for MRI-Guided Tumor Therapy

Molecular, Macromolecular, and Supramolecular Glucuronide Prodrugs: Lead Identified for Anticancer Prodrug Monotherapy

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