The fine-tuning of thermosensitive and degradable polymer micelles for enhancing intracellular uptake and drug release in tumors

Li, Wei; Li, Jinfeng; Gao, Jie; Li, Bohua; Xia, Yu; Meng, Yanchun; Yu, Yongsheng; Chen, Huaiwen; Dai, Jing; Wang, Hao; Guo, Yajun

doi:10.1016/j.biomaterials.2011.01.075

Cited by 125 publications

(90 citation statements)

References 41 publications

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“…[270][271][272] the use of trithiocarbonate 140 to carry out simultaneous RAFT polymerization of St and ROP of lactide. [421] The product was used as a macromonomer in ROMP.…”

Section: Rop-raftmentioning

confidence: 99%

Living Radical Polymerization by the RAFT Process – A Third Update

2012

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This paper provides a third update to the review of reversible deactivation radical polymerization (RDRP) achieved with thiocarbonylthio compounds (ZC(¼S)SR) by a mechanism of reversible addition-fragmentation chain transfer ( Chem. 2009Chem. , 62, 1402. This review cites over 700 publications that appeared during the period mid 2009 to early 2012 covering various aspects of RAFT polymerization which include reagent synthesis and properties, kinetics and mechanism of polymerization, novel polymer syntheses, and a diverse range of applications. This period has witnessed further significant developments, particularly in the areas of novel RAFT agents, techniques for end-group transformation, the production of micro/nanoparticles and modified surfaces, and biopolymer conjugates both for therapeutic and diagnostic applications.

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“…[270][271][272] the use of trithiocarbonate 140 to carry out simultaneous RAFT polymerization of St and ROP of lactide. [421] The product was used as a macromonomer in ROMP.…”

Section: Rop-raftmentioning

confidence: 99%

Living Radical Polymerization by the RAFT Process – A Third Update

2012

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“…28,29 The PID 118 -b-PLA 39 block copolymer (~10 mg) was dissolved in 1.5 mL DMAC and then dialyzed against Milli-Q water using the dialysis membrane (MWCO =1,000 D) at 24°C for 48 hours with regular water changing. The hydrodynamic diameter and size distribution were determined by ZetaSizer Nano-ZS (Malvern Instruments, Malvern, UK).…”

Section: Self-assembly Of Tnsmentioning

confidence: 99%

“…27 The pH-regulated degradation endows its function that controls the intracellular drug release in the lesion sites, which can enhance therapeutic efficacy. 28,29 Therefore, it is easy to find that micelles with temperature-responsive and degradable merits are a promising platform for shikonin delivery. In the further study, it was found that improving the in vivo passive targeting and cellular uptake is still a big challenge in practical application.…”

Section: Introductionmentioning

confidence: 99%

“…A reversible addition-fragmentation chain transfer (RAFT) agent, 2-(N-[2-hydroxyethyl]carbamoyl) prop-2-yl dithiobenzoate (HECPD), was prepared according to previous publications. 28,[31][32][33] The water used was purified by a Milli-Q water purification system (EMD Millipore, Billerica, MA, USA). The dialysis membrane was provided by Spectrum Medical Industries (Los Angeles, CA, USA).…”

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confidence: 99%

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Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle

Su¹,

Huang²,

Chen³

et al. 2017

IJN

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The Chinese traditional medicine Shikonin is an ideal drug due to its multiple targets to tumor cells. But in clinics, improving its aqueous solubility and tumor accumulation is still a challenge. Herein, a copolymer with tunable poly(N-isopropylacrymaide) and polylactic acid block lengths is designed, synthesized, and characterized in nuclear magnetic resonance. The corresponding thermosensitive nanomicelle (TN) with well-defined core-shell structure is then assembled in an aqueous solution. For promoting the therapeutic index, the physical-chemistry properties of TNs including narrow size, low critical micellar concentration, high serum stability, tunable volume phase transition temperature (VPTT), high drug-loading capacity, and temperature-controlled drug release are systematically investigated and regulated through the fine self-assembly. The shikonin is then entrapped in a degradable inner core resulting in a shikonin-loaded thermosensitive nanomicelle (STN) with a VPTT of ~40°C. Compared with small-molecular shikonin, the in vitro cellular internalization and cytotoxicity of STN against breast cancer cells (Michigan Cancer Foundation-7) are obviously enhanced. In addition, the therapeutic effect is further enhanced by the programmed cell death (PCD) specifically evoked by shikonin. Interestingly, both the proliferation inhibition and PCD are synergistically promoted as T > VPTT, namely the temperature-regulated passive targeting. Consequently, as intravenous injection is administered to the BALB/c nude mice bearing breast cancer, the intratumor accumulation of STNs is significantly increased as T > VPTT, which is regulated by the in-house developed heating device. The in vivo antitumor assays against breast cancer further confirm the synergistically enhanced therapeutic efficiency. The findings of this study indicate that STN is a potential effective nanoformulation in clinical cancer therapy.

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“…Another system has shown responsiveness to both ultrasound and enzymes to enhance drug release from bubble liposomes (Nahire et al, 2012). Nano-carriers responding to dual-stimuli have also been studied including pH and temperature responsive P(NIPAAm-co-DMAAmco-UA) and P(NIPAAm-co-DMAAm-co-UA)-g-cholesterol NPs loaded with DOX (Soppimath et al, 2005(Soppimath et al, , 2007, paclitoxel-loaded P(NIPAAm-co-AA)-b-PCL NPs (Zhang et al, 2007), mPEG-b-P(HPMA-Lac-co-His), mPEG-b-PLA and cy5.5-PEG-PLA mixed micelles carrying DOX (Chen et al, 2012), PLA-g-P(NIPAAm-co-MAA) and P(NIPAAmco-DMAAm)-b-PCL/PLA micelles carrying adriamycin (Li et al, 2011). A number of examples of pH and magnetic sensitive drug releasing systems include Fe3O4 nanocarriers coated with peptide mimic polymers loaded with DOXÁHCI (Barick et al, 2012) DOX-tethered Fe3O4 conjugates and mPEG-b-PMAA-b-PGMA-Fe3O4 NPs conjugated with adriamycin (Guo et al, 2008).…”

Section: Magnetic-responsive Polymersmentioning

confidence: 99%

Classification of stimuli–responsive polymers as anticancer drug delivery systems

et al. 2014

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Although several anticancer drugs have been introduced as chemotherapeutic agents, the effective treatment of cancer remains a challenge. Major limitations in the application of anticancer drugs include their nonspecificity, wide biodistribution, short half-life, low concentration in tumor tissue and systemic toxicity. Drug delivery to the tumor site has become feasible in recent years, and recent advances in the development of new drug delivery systems for controlled drug release in tumor tissues with reduced side effects show great promise. In this field, the use of biodegradable polymers as drug carriers has attracted the most attention. However, drug release is still difficult to control even when a polymeric drug carrier is used. The design of pharmaceutical polymers that respond to external stimuli (known as stimuli-responsive polymers) such as temperature, pH, electric or magnetic field, enzymes, ultrasound waves, etc. appears to be a successful approach. In these systems, drug release is triggered by different stimuli. The purpose of this review is to summarize different types of polymeric drug carriers and stimuli, in addition to the combination use of stimuli in order to achieve a better controlled drug release, and it discusses their potential strengths and applications. A survey of the recent literature on various stimuli-responsive drug delivery systems is also provided and perspectives on possible future developments in controlled drug release at tumor site have been discussed.

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The fine-tuning of thermosensitive and degradable polymer micelles for enhancing intracellular uptake and drug release in tumors

Cited by 125 publications

References 41 publications

Living Radical Polymerization by the RAFT Process – A Third Update

Living Radical Polymerization by the RAFT Process – A Third Update

Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle

Classification of stimuli–responsive polymers as anticancer drug delivery systems

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