Development of polymeric micelles for targeting intractable cancers

Nishiyama, Nobuhiro; Matsumura, Yasuhiro; Kataoka, Kazunori

doi:10.1111/cas.12960

Cited by 154 publications

(91 citation statements)

References 81 publications

(300 reference statements)

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“…Nano‐sized delivery systems such as polymer carriers, liposomes, micelles and nanogels have recently been widely used. They have passive targeting characteristics by an enhanced permeation and retention (EPR) effect.…”

Section: Introductionmentioning

confidence: 99%

Hypocrellin B‐loaded, folate‐conjugated polymeric micelle for intraperitoneal targeting of ovarian cancer in vitro and in vivo

Yao

Wang

et al. 2018

Cancer Science

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Photodynamic therapy (PDT) is considered an innovative and attractive modality to treat ovarian cancer. In the present study, a biodegradable polymer poly (ethylene glycol) (PEG)‐poly (lactic acid)(PLA)‐folate (FA‐PEG‐PLA) was prepared in order to synthesize an active‐targeting, water‐soluble and pharmacomodulated photosensitizer nanocarrier. Drug‐loading content, encapsulation efficiency, in vitro and in vivo release were characterized, in which hypocrellin B (HB)/FA‐PEG‐PLA micelles had a high encapsulation efficiency and much slower control release for drugs compared to free drugs (P < .05). To evaluate the targeting ability of the HB/FA‐PEG‐PLA micelles, a cellular uptake study in vitro was carried out, which showed significantly enhanced uptake of HB/FA‐PEG‐PLA micelles in SKOV3 (FR+) compared to A2780 cancer cells (FR−). The enhanced uptake of HB/FA‐PEG‐PLA micelles to cancer cells resulted in a more effective post‐PDT killing of SKOV3 cells compared to plain micelles and free drugs. Binding and uptake of HB/FA‐PEG‐PLA micelles by SKOV3 cells were also observed in vivo after ip injection of folate‐targeted micelles in tumor‐bearing ascitic ovarian cancer animals. Drug levels in ascitic tumor tissues were increased 20‐fold (P < .001), which underscored the effect of a regional therapy approach with folate targeting. Furthermore, the HB‐loaded micelles were mainly distributed in kidney and liver (the main clearance organs) in biodistribution. These results showed that our newly developed PDT photosensitizer HB/FA‐PEG‐PLA micelles have a high drug‐loading capacity, good biocompatibility, controlled drug release, and enhanced targeting and antitumor effect, which is a potential approach to future targeting ovarian cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Hypocrellin B‐loaded, folate‐conjugated polymeric micelle for intraperitoneal targeting of ovarian cancer in vitro and in vivo

Yao

Wang

et al. 2018

Cancer Science

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“…The following procedure was used for the synthesis of star polymer (PNVCL 30 ) 6 : CTA-1 (0.12 g, 0.092 mmol), VAc (2 g, 23.2 mmol) and 4,4-azobis(4-cyanovaleric acid) (2.5 mg, 0.009 mmol) were dissolved in 1.5 mL of p-dioxane. This mixture was transferred to a Schlenk flask containing a magnetic stir bar.…”

Section: Preparation Of Star (Pvac) Polymers With Six Armsmentioning

confidence: 99%

Preparation of a Mini-Library of Thermo-Responsive Star (NVCL/NVP-VAc) Polymers with Tailored Properties Using a Hexafunctional Xanthate RAFT Agent

Cortez-Lemus

Licea‐Claveríe

2017

Polymers

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Abstract:A mini-library of star-shaped thermoresponsive polymers having six arms was prepared using a hexafunctional xanthate by reversible addition-fragmentation chain transfer (RAFT) polymerization. Star polymers with homopolymeric arms of poly(N-vinylcaprolactam) (PNVCL), copolymeric arms of poly(N-vinylcaprolactam-co-N-vinylpyrrolidone) (PNVCL-co-PNVP) and also arms of block copolymers of PNVCL-b-PVAc, (PNVCL-co-PNVP)-b-PVAc, and combinations of them changing the order of the block was achieved exploiting the R-RAFT synthetic methodology (or R-group approach), wherein the thiocarbonyl group is transferred to the polymeric chain end. Taking advantage of the RAFT benefits, the molecular weight of the star polymers was controlled (M n = 11,880-153,400 g/mol) to yield star polymers of different sizes and lower critical solution temperature (LCST) values. Removing the xanthate group of the star polymers allowed for the introduction of specific functional groups at the ends of the star arms and resulted in an increase of the LCST values. Star PNVCL-b-PVAc diblock copolymers with PVAc contents of 5-26 mol % were prepared; the hydrophobic segment (PVAc) is located at the end of the star arms. Interestingly, when the PVAc content was 5-7 mol %, the hydrodynamic diameter (D h ) value of the aggregates formed in water was almost the same sa the D h of the corresponding PNVCL star homopolymers. It is proposed that these star block copolymers self-assemble into single flowerlike micelles, showing great stability in aqueous solution. Star block copolymers with the PVAc hydrophobic block in the core of the star, such as PVAc-b-(PNVCL-co-PNVP), form micellar aggregates in aqueous solution with D h values in the range from~115 to 245 nm while maintaining a thermoresponsive behavior. Micellar aggregates of selected star polymers were used to encapsulate methotrexate (MTX) showing their potential in the temperature controlled release of this antineoplasic drug. The importance of the order in which each block constituent is introduced in the arms of the star polymers for their solution/aggregation behavior is demonstrated.

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“…Nevertheless, polymeric micelles have been mainly studied as delivering systems for anticancer drugs [113,114]; they are convenient devices for transport of plasmid DNA, oligonucleotides [115] or diagnostic agents [116].…”

Section: Slika 4 Agregati Na Bazi Poli(dl-mlečna Kiselina)-poli(elilmentioning

confidence: 99%

Biodegradable polymers suitable for tissue engineering and drug delivery systems

Porjazoska-Kujundziski¹,

Chamovska²

2017

Zas Mat

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Development of polymeric micelles for targeting intractable cancers

Cited by 154 publications

References 81 publications

Hypocrellin B‐loaded, folate‐conjugated polymeric micelle for intraperitoneal targeting of ovarian cancer in vitro and in vivo

Hypocrellin B‐loaded, folate‐conjugated polymeric micelle for intraperitoneal targeting of ovarian cancer in vitro and in vivo

Preparation of a Mini-Library of Thermo-Responsive Star (NVCL/NVP-VAc) Polymers with Tailored Properties Using a Hexafunctional Xanthate RAFT Agent

Biodegradable polymers suitable for tissue engineering and drug delivery systems

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