Self-crosslinkable and intracellularly decrosslinkable biodegradable micellar nanoparticles: A robust, simple and multifunctional nanoplatform for high-efficiency targeted cancer chemotherapy

Zou, Yan; Fang, Yiping; Meng, Hao; Meng, Fenghua; Deng, Chao; Zhang, Jian; Zhong, Zhiyuan

doi:10.1016/j.jconrel.2016.05.060

Cited by 84 publications

(101 citation statements)

References 53 publications

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“…All the above results point out that cRGD‐PS‐DM1 nano‐prodrug has a superior antitumor efficacy to the nontargeting PS‐DM1 counterpart in B16F10 tumor‐bearing mice. We and others have shown that cRGD can actively target to B16F10 melanoma in vivo . It should be noted, nevertheless, that tumor targetability of ligand‐functionalized nanoparticles is highly dependent on nature of tumor, type and size of nanoparticles, type of ligand, ligand surface density, and ligand orientation .…”

Section: Resultsmentioning

confidence: 83%

“…cRGD‐PS‐DM1 nano‐prodrug was readily fabricated from PEG‐ b ‐P(TMC‐ co ‐DTC) and cRGD‐PEG‐ b ‐P(TMC‐ co ‐DTC) (w/w 80/20) with simultaneous loading of DM1 via thiol–disulfide exchange reaction and disulfide cross‐linking of polymersomal membrane. PEG‐ b ‐P(TMC‐ co ‐DTC) and cRGD‐PEG‐ b ‐P(TMC‐ co ‐DTC) block copolymers were synthesized via ring‐opening polymerization of dithiolane trimethylene carbonate (DTC) with trimethylene carbonate (TMC) (Scheme S1, Supporting Information), according to previous reports with slight modifications . The M n of P(TMC‐ co ‐DTC) block can be estimated by 1 H NMR (Figure S1, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

“…cRGD‐PEG‐ b ‐P(TMC‐ co ‐DTC) was synthesized according to previous reports with slight modifications . First, NHS‐PEG‐ b ‐P(TMC‐ co ‐DTC) was synthesized by ring‐opening copolymerization of TMC and DTC monomers.…”

Section: Methodsmentioning

confidence: 99%

“…Several disulfide‐cross‐linked nanosystems have demonstrated an enhanced stability under a physiological condition, while are prone to fast reductive degradation in the cytoplasm . Interestingly, self‐cross‐linkable and intracellular de‐cross‐linkable micellar nanoparticles and vesicles were recently developed for tumor‐targeted delivery of doxorubicin …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A Smart Nano‐Prodrug Platform with Reactive Drug Loading, Superb Stability, and Fast Responsive Drug Release for Targeted Cancer Therapy

Meng

Zou

Zhong

et al. 2017

Macromolecular Bioscience

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Nano-prodrugs usually involve a multistep synthesis which largely compromises their benefits. Here, a smart nano-prodrug platform with reactive drug loading, superb stability, and triggered drug release is reported for targeted melanoma therapy. cRGD-decorated polymersomal mertansine prodrug (cRGD-PS-DM1) is readily fabricated from cRGD-functionalized poly(ethylene glycol)-b-poly(trimethylene carbonate-co-dithiolane trimethylene carbonate) with simultaneous loading of mertansine (DM1) via thiol-disulfide exchange reaction and disulfide cross-linking of polymersomal membrane. cRGD-PS-DM1 exhibits a size of ≈100 nm, little drug leakage, and fast DM1 release in the presence of 2 × 10 −3 -10 × 10 −3 m glutathione. Tetrazolium-based colorimetric assay (MTT) and confocal microscopy studies confirm effective homing of cRGD-PS-DM1 to α v β 3 overexpressing B16F10 melanoma cells. Notably, the in vivo studies show that cRGD-PS-DM1 has a greatly improved toleration as compared with free DM1 and effectively inhibits tumor growth and extends the survival time of B16F10 melanoma-bearing mice. cRGD-PS-DM1 nanoprodrug with reactive drug loading and multifunction provides an advanced nanomedicine for cancer therapy.

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Section: Resultsmentioning

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A Smart Nano‐Prodrug Platform with Reactive Drug Loading, Superb Stability, and Fast Responsive Drug Release for Targeted Cancer Therapy

Meng

Zou

Zhong

et al. 2017

Macromolecular Bioscience

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“…Interestingly, (7 of 26) 1700022 DOX-loaded micelles showed high stability, minimal drug leakage, long circulation time, and triggered-drug release inside the tumor cells. [99] In addition to disulfide bond, the diselenide linker has also been used to prepare reversible cross-linked polymer nanoparticles. Deepagan et al, for instance, prepared diselenide-cross-linked micelles by using selenol-bearing triblock copolymers consisting of PEG and polypeptide derivatives.…”

Section: Endosomes/ Lysosomesmentioning

confidence: 99%

Controlling and Monitoring Intracellular Delivery of Anticancer Polymer Nanomedicines

Battistella

Klok

2017

Macromolecular Bioscience

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Polymer nanomedicines are very attractive to improve the delivery of chemotherapeutics. Polymer conjugates and other polymer‐based nanocarriers allow to increase plasma half‐life and drug bioavailability and can also be guided toward tumors using passive and active targeting strategies. Since many chemotherapeutics act on targets that are located in well‐defined subcellular compartments, other important factors that contribute to an efficient therapy include cellular internalization and subsequent intracellular trafficking of the polymer nanomedicines and/or its payload to the appropriate organelle in the cytoplasm. This article provides an overview of the different approaches that have been developed to control intracellular delivery of polymer nanomedicines and discusses the different techniques that can be used to monitor these processes.

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Ultralong Circulating Lollipop‐Like Nanoparticles Assembled with Gossypol, Doxorubicin, and Polydopamine via π–π Stacking for Synergistic Tumor Therapy

et al. 2018

Adv Funct Materials

103

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Long blood circulation in vivo remains a challenge to dual-drug-loaded nanocarriers for synergistic chemotherapy. Herein, a novel strategy to prepare lollipop-like dual-drug-loaded nanoparticles (DOX-PDAgossypol NPs) is developed based on the self-assembly of gossypol, doxorubicin (DOX), and polydopamine (PDA) via π-π stacking. Dopamine polymerizes to PDA and fills the gaps between the gossypol and DOX molecules to form the super compact long-circulating nanoparticles. The DOX-PDA-gossypol NPs show a suitable particle size of 59.6 ± 9.6 nm, high drug loading of 91%, superb stability, high maximum-tolerated dose (MTD) of over 60 mg kg -1 , and negligible toxicity. These NPs also exhibit pH-dependent drug release and low combination index (0.23). Notably, they show dramatically ultralong blood circulation (>192 h) with elimination half times 458-fold and 258-fold longer than that of free DOX and free gossypol, respectively. These values are markedly higher than most of the reported results. Therefore, the DOX-PDA-gossypol NPs have a high tumor accumulation of 12% remaining on the 8th day postinjection. This characteristic contributes to the excellent tumor comprehensive synergistic therapeutic efficacy (TIR > 90%) with low administration dosage and is benefitted for widening the drug therapeutic window. Thus, the proposed strategy has remarkable potential for tumor synergistic therapy.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adfm.201805582. Recent studies have developed various methods to prolong the blood circulation of NCS. These methods mainly include the surface modification of hydrophilic polymers or nonionic Tumor Therapy

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Self-crosslinkable and intracellularly decrosslinkable biodegradable micellar nanoparticles: A robust, simple and multifunctional nanoplatform for high-efficiency targeted cancer chemotherapy

Cited by 84 publications

References 53 publications

A Smart Nano‐Prodrug Platform with Reactive Drug Loading, Superb Stability, and Fast Responsive Drug Release for Targeted Cancer Therapy

A Smart Nano‐Prodrug Platform with Reactive Drug Loading, Superb Stability, and Fast Responsive Drug Release for Targeted Cancer Therapy

Controlling and Monitoring Intracellular Delivery of Anticancer Polymer Nanomedicines

Ultralong Circulating Lollipop‐Like Nanoparticles Assembled with Gossypol, Doxorubicin, and Polydopamine via π–π Stacking for Synergistic Tumor Therapy

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