Herein, we present a series of light-triggered porphyrin-based polymeric drug conjugates PSDTD-m for combined chemo-photodynamic therapy of cancer. The controlled release of a drug through a ROS-cleavable linker combined with photodynamic therapy showed enhanced anticancer efficacy, proving the effectiveness of this light triggered smart nanocarrier platform for enhancing the therapy efficacy.
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.
Herein, a kind of dual acid-sensitive nanoparticles based on monomethoxy poly(ethylene glycol)-imine-β-cyclodextrin is constructed by a facile phenylboronic acid-cross-linked way. The data of dynamic light scattering and transmission electron microscope reveal the cross-linked nanoparticles have improved stability. The cross-linked nanoparticles could easily self-assemble and load the anticancer drug at neutral pH condition. However, when the drug-loaded nanoparticles are delivered to extracellular tumor sites (pH ≈6.8), the surface of the nanoparticles would be amino positively charged and easily internalized by tumor cell due to the cleavage of the acid-labile benzoic-imine. Subsequently, with the acidity in subcellular compartments significantly increasing (such as the endosome pH ≈5.3), the loaded drug would fast release from the endocytosis carriers due to the hydrolysis of boronate ester. These features suggest that these dual acid-sensitive cross-linked nanoparticles not only possess excellent biocompatibility but also can efficiently load and deliver anticancer drug into tumor cells to enhance the inhibition of cellular proliferation, outlining a favorable platform as drug carriers.
Herein, hyperbranched poly(ethylene glycol)-based supramolecular nanoparticles with pH-sensitive properties were designed and used for targeted drug delivery. Via host-guest recognition between benzimidazole anchored poly(ethylene glycol)-hyperbranched polyglycerol (PEG-HPG-BM) and folic acid modified CD (FA-CD), targeted supramolecular nanoparticles (TSNs) were fabricated. At neutral aqueous conditions TSNs could load the model drug DOX. While under intracellular acidic conditions the loaded-drug would be released due to the protonation of BM. This protonation allowed the supramolecular nanoparticles to expand or even disassemble, which showes the pH-dependent property. The introduction of the active targeting FA molecule and the specific interactions with the receptor of HeLa cells means that DOX-loaded TSNs show a significantly improved anticancer efficacy. In vitro drug release assays and intracellular experiments confirmed that TSNs had an obvious pH-sensitive property and remarkably improved anticancer effects, which hold great potential for further biomedical applications such as anticancer drug delivery.
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