Multifunctional Core‐Shell‐Corona‐Type Polymeric Micelles for Anticancer Drug‐Delivery and Imaging

Bastakoti, Bishnu Prasad; Wu, Kevin C.‐W.; Inoue, Masamichi; Yusa, Shin‐ichi; Nakashima, Kenichi; Yamauchi, Yusuke

doi:10.1002/chem.201203958

Cited by 66 publications

(45 citation statements)

References 57 publications

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“…Controlled living free radical polymerization techniques have been increasingly used in the synthesis of well-defined polymers for investigating structure-function relationship of drug and gene delivery systems [42][43][44][45][46]. We have reported recently multi-step synthesis of star block copolymers based unimolecular micelles as templates for in situ formation of gold nanoparticles [32].…”

Section: Synthesis and Characterization Of The Star Block Copolymermentioning

confidence: 99%

Co-Delivery of Imiquimod and Plasmid DNA via an Amphiphilic pH-Responsive Star Polymer that Forms Unimolecular Micelles in Water

Lin

Yao

et al. 2016

Polymers

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Dual functional unimolecular micelles based on a pH-responsive amphiphilic star polymer β-CD-(PLA-b-PDMAEMA-b-PEtOxMA) 21 have been developed for the co-delivery of imiquimod and plasmid DNA to dendritic cells. The star polymer with well-defined triblock arms was synthesized by combining activator regenerated by electron-transfer atom-transfer radical polymerization with ring-opening polymerization. Dissipative particle dynamics simulation showed that core-mesophere-shell-type unimolecular micelles could be formed. Imiquimod-loaded micelles had a drug loading of 1.6 wt % and a larger average size (28 nm) than blank micelles (19 nm). The release of imiquimod in vitro was accelerated at the mildly acidic endolysosomal pH (5.0) in comparison to physiologic pH (7.4). Compared with blank micelles, a higher N:P ratio was required for imiquimod-loaded micelles to fully condense DNA into micelleplexes averaging 200-400 nm in size. In comparison to blank micelleplexes, imiquimod-loaded micelleplexes of the same N:P ratio displayed similar or slightly higher efficiency of gene transfection in a mouse dendritic cell line (DC2.4) without cytotoxicity. These results suggest that such pH-responsive unimolecular micelles formed by the well-defined amphiphilic star polymer may serve as promising nano-scale carriers for combined delivery of hydrophobic immunostimulatory drugs (such as imiquimod) and plasmid DNA with potential application in gene-based immunotherapy.

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Section: Synthesis and Characterization Of The Star Block Copolymermentioning

confidence: 99%

Co-Delivery of Imiquimod and Plasmid DNA via an Amphiphilic pH-Responsive Star Polymer that Forms Unimolecular Micelles in Water

Lin

Yao

et al. 2016

Polymers

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“…Bastakoti et al [101] prepared core-shell-corona-type polymeric micelles of asymmetric triblock copolymer (poly(styrene-acrylic acid-ethylene glycol) (PS-PAA-PEG) with multiple functions, which included the ability to accommodate hydrophobic dyes into the core and hydrophilic drug into the shell in addition to pH-triggered drug release. The neutral and hydrophilic corona sterically stabilized the multifunctional polymeric micelles in Figure 12.…”

Section: Inorganic/organic-composite Ph-responsive Drug-delivery Systemsmentioning

confidence: 99%

pH‐Responsive Drug‐Delivery Systems

Zhu

Chen

2014

Chemistry An Asian Journal

168

104

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In many biomedical applications, drugs need to be delivered in response to the pH value in the body. In fact, it is desirable if the drugs can be administered in a controlled manner that precisely matches physiological needs at targeted sites and at predetermined release rates for predefined periods of time. Different organs, tissues, and cellular compartments have different pH values, which makes the pH value a suitable stimulus for controlled drug release. pH-Responsive drug-delivery systems have attracted more and more interest as "smart" drug-delivery systems for overcoming the shortcomings of conventional drug formulations because they are able to deliver drugs in a controlled manner at a specific site and time, which results in high therapeutic efficacy. This focus review is not intended to offer a comprehensive review on the research devoted to pH-responsive drug-delivery systems; instead, it presents some recent progress obtained for pH-responsive drug-delivery systems and future perspectives. There are a large number of publications available on this topic, but only a selection of examples will be discussed.

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“…Bastakoti et al developed multifunctional core-shell-corona polymeric micelles using a special type of asymmetric tri-block copolymer poly(styrene-acrylic acid-ethylene glycol) (PS-PAA-PEG) (Bastakoti et al, 2013). The self assembly of PS-PAA-PEG in aqueous solutions produces micelles with a PS core, an anionic PAA shell and a neutral and hydrophilic PEG corona.…”

Section: Multifunctional Polymeric Micellesmentioning

confidence: 99%

Multifunctional polymeric micelles for delivery of drugs and siRNA

2014

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Polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers with a core-shell structure have been used as versatile carriers for delivery of drugs as well as nucleic acids. They have gained immense popularity owing to a host of favorable properties including their capacity to effectively solubilize a variety of poorly soluble pharmaceutical agents, biocompatibility, longevity, high stability in vitro and in vivo and the ability to accumulate in pathological areas with compromised vasculature. Moreover, additional functions can be imparted to these micelles by engineering their surface with various ligands and cell-penetrating moieties to allow for specific targeting and intracellular accumulation, respectively, to load them with contrast agents to confer imaging capabilities, and incorporating stimuli-sensitive groups that allow drug release in response to small changes in the environment. Recently, there has been an increasing trend toward designing polymeric micelles which integrate a number of the above functions into a single carrier to give rise to “smart,” multifunctional polymeric micelles. Such multifunctional micelles can be envisaged as key to improving the efficacy of current treatments which have seen a steady increase not only in hydrophobic small molecules, but also in biologics including therapeutic genes, antibodies and small interfering RNA (siRNA). The purpose of this review is to highlight recent advances in the development of multifunctional polymeric micelles specifically for delivery of drugs and siRNA. In spite of the tremendous potential of siRNA, its translation into clinics has been a significant challenge because of physiological barriers to its effective delivery and the lack of safe, effective and clinically suitable vehicles. To that end, we also discuss the potential and suitability of multifunctional polymeric micelles, including lipid-based micelles, as promising vehicles for both siRNA and drugs.

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Multifunctional Core‐Shell‐Corona‐Type Polymeric Micelles for Anticancer Drug‐Delivery and Imaging

Cited by 66 publications

References 57 publications

Co-Delivery of Imiquimod and Plasmid DNA via an Amphiphilic pH-Responsive Star Polymer that Forms Unimolecular Micelles in Water

Co-Delivery of Imiquimod and Plasmid DNA via an Amphiphilic pH-Responsive Star Polymer that Forms Unimolecular Micelles in Water

pH‐Responsive Drug‐Delivery Systems

Multifunctional polymeric micelles for delivery of drugs and siRNA

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