Nanocarriers with dual pH-sensitivity for enhanced tumor cell uptake and rapid intracellular drug release

Wu, Wei; Miao, Chang; Wang, Jiantao; Zhang, Qiujing; Li, Shuai; Lin, Zaifu; Li, Jianshu

doi:10.1039/c4ra05270f

Cited by 22 publications

(25 citation statements)

References 37 publications

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“…13 Then the surface of DOX-loaded supramolecular nanoparticles will exhibit a positively charged amino. It is known that most extracellular pH at the solid tumor site is 6.8, therefore, the acid-labile linkage is active and responds to the pH effectively.…”

Section: Intracellular Dox Release and Cellular Proliferation Inhibitionmentioning

confidence: 99%

Dual acid-responsive supramolecular nanoparticles as new anticancer drug delivery systems

et al. 2016

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Considering the specific pH gradients of tumour microenvironments, a dual acid-responsive drug delivery system, which can respond to the tumor extracellular and intercellular pH stimuli, has been fabricated via simple host-guest recognition. Firstly, we synthesise 2,4,6-trimethoxybenzaldehyde modified dextran (Dex-TMBA) and mPEG-imine-β-cyclodextrin (PIC), respectively. And then, through the host-guest recognition between the cyclodextrin (CD) of PIC and the benzene ring of Dex-TMBA, a kind of dual acid-responsive supramolecular drug delivery system can be fabricated. Under neutral pH conditions, anticancer drugs can be loaded by forming supramolecular nanoparticles via the host-guest recognition. While, at tumor extracellular pH (∼6.8), the acid-labile benzoic-imine of PIC cleaves and the nanoparticles are amino positively charged to facilitate cell internalization. Subsequently, due to the hydrolysis of acetal bonds in Dex-TMBA under significantly increased acidity in subcellular compartments such as the endosomes (∼5.3), the loaded doxorubicin releases from the endocytosed drug delivery. This dual acid-responsive nanoparticles can efficiently load and release drugs, acting as drug delivery systems for enhancing anticancer efficiency.

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Section: Intracellular Dox Release and Cellular Proliferation Inhibitionmentioning

confidence: 99%

Dual acid-responsive supramolecular nanoparticles as new anticancer drug delivery systems

et al. 2016

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“…It is thus paramount to equip nanocarriers with the “on‐demand” cargo‐releasing properties to achieve spatial‐, time‐, and dosage‐controlled drug release profiles via diffusion‐, solvent‐, degradation‐, or stimuli‐controlled manner . For instance, pH‐responsive micelles based on amphiphilic diblock copolymer poly(2‐diisopropylaminoethyl methacrylate)‐ b ‐poly(2‐aminoethyl methacrylate hydrochloride) (PDPA‐ b ‐PAMA) could release drugs swiftly after a contact with the intracellular acidity of endo‐/lysosome (pH values of 5.5–6.0 and 4.5–5.0, respectively) …”

Section: Nanoparticle Design Aimsmentioning

confidence: 99%

Atherosclerosis Treatment with Stimuli‐Responsive Nanoagents: Recent Advances and Future Perspectives

Maruf

Wang

Yin

et al. 2019

Adv Healthcare Materials

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Atherosclerosis is the root of approximately one‐third of global mortalities. Nanotechnology exhibits splendid prospects to combat atherosclerosis at the molecular level by engineering smart nanoagents with versatile functionalizations. Significant advances in nanoengineering enable nanoagents to autonomously navigate in the bloodstream, escape from biological barriers, and assemble with their nanocohort at the targeted lesion. The assembly of nanoagents with endogenous and exogenous stimuli breaks down their shells, facilitates intracellular delivery, releases their cargo to kill the corrupt cells, and gives imaging reports. All these improvements pave the way toward personalized medicine for atherosclerosis. This review systematically summarizes the recent advances in stimuli‐responsive nanoagents for atherosclerosis management and its progress in clinical trials.

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“…Compared with a system with physically loaded drug, drug‐conjugated one through cleavable covalent bond shows better stable prior to receiving a specific stimulus signal . Considering that doxorubicin (DOX) is one of the most commonly used chemotherapeutic agent and is widely used in cancer therapy, it is very meaningful to conjugate DOX into a β‐CD‐core star copolymer to form a novel drug delivery system with direct water‐solubility.…”

Section: Introductionmentioning

confidence: 99%

Dual pH‐Sensitive DOX‐Conjugated Cyclodextrin‐Core Star Nano‐Copolymer Prodrugs

Hou

Liu

Sun

et al. 2017

Macro Chemistry & Physics

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Herein this study reports dual pH‐sensitive doxorubicin (DOX)‐conjugated β‐cyclodextrin‐core star copolymers with tailoring properties such as direct water‐solubility and stability prior to reaching target sites. For these purposes, three kinds of novel well‐defined β‐cyclodextrin‐core poly(2‐(diethylamino)ethyl methacrylate‐co‐4‐formylphenyl methacrylate)‐b‐poly(poly(ethylene glycol) methyl ether methacrylate) star copolymers (CD‐star‐P(DEA‐co‐FPMA)‐b‐PPEGMA, SPDFP1–3) with different poly(ethylene glycol) methyl ether methacrylate contents are designed and synthesized by atom transfer radical polymerization (ATRP) strategy. 4‐Formylphenyl methacrylate is introduced into the inner arm block of the star copolymers for conjugating DOX by imine bond formation. Interestingly, the DOX‐conjugated β‐cyclodextrin‐core star copolymers not only can directly dissolve in aqueous buffer solution of pH 7.0 to form unimolecular micelles without any aid of organic solvent, but also exhibit strong pH‐dependent DOX release. At normal pH 7.4 the DOX amount released is very small, whereas at pH 5.0 DOX can be released. By selecting SPDFP2–DOX as a representative, it is found that the SPDFP2–DOX micelles show less cytotoxicity compared to carrier‐free DOX and can be internalized by HeLa cells. It is expected that the exploration can provide new strategy for preparing drug delivery system.

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Nanocarriers with dual pH-sensitivity for enhanced tumor cell uptake and rapid intracellular drug release

Abstract: Block polymers are synthesized to prepare nanocarriers with dual pHsensitivity, which are expected to prolong blood circulation time, reduce systemic toxicity, enhance tumor cell uptake and accelerate intracellular drug release for efficient anti-cancer therapy.

Cited by 22 publications

References 37 publications

Dual acid-responsive supramolecular nanoparticles as new anticancer drug delivery systems

Dual acid-responsive supramolecular nanoparticles as new anticancer drug delivery systems

Atherosclerosis Treatment with Stimuli‐Responsive Nanoagents: Recent Advances and Future Perspectives

Dual pH‐Sensitive DOX‐Conjugated Cyclodextrin‐Core Star Nano‐Copolymer Prodrugs

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