This study develops novel pH and reduction dual-sensitive micelles for the anticancer drug doxorubicin (DOX) delivery owing to the fact that the tumor tissues show low pH and high reduction environment. These sub-100 nm micelles present a core-shell structure under physiological conditions, but quickly release the loaded drugs responding to acidic and reductive stimuli. With disulfide bonds in each repeat unit of poly(β-amino ester)s, the novel copolymer was synthesized via Michael addition polymerization from 2,2'-dithiodiethanol diacrylate, 4,4'-trimethylene dipiperidine, and methoxy-PEG-NH(2). DOX released faster from micelles in a weakly acidic environment (pH 6.5) than at pH 7.4 or in the presence of a higher concentration (5 mM) of reducing agent (DTT). The release is even more effective in a scenario of both stimuli (pH 6.5 and 5 mM DTT). MTT assay showed that the DOX-loaded micelles had a higher cytotoxicity for HepG2 tumor cells than DOX at higher concentrations, and that blank micelles had a very low cytotoxicity to the tumor cells. Confocal microscopy observation showed that the micelles can be quickly internalized, effectively deliver the drugs into nuclei, and inhibit cell growth. These results present the copolymer as a novel and effective pH and reduction dual-responsive nanocarrier to enhance drug efficacy for cancer cells.

Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction.

The engineered cardiac patch (ECP) is a promising strategy to repair infarct myocardium and restore the cardiac function. An ideal ECP should be able to mimic the primary attributes of native myocardium, which includes a high resilience, good cardiomyocyte adhesion, and synchronous contraction. Here, a mussel‐inspired dopamine crosslinker is used to integrate polypyrrole (Ppy) nanoparticles, gelatin‐methyacrylate, and poly(ethylene glycol) diacrylate into a cryogel form. The dopamine crosslinker and Ppy nanoparticles are coordinated to obtain optimal mechanical and superelastic properties for the ECP. The dopamine facilitates the uniform distribution of the Ppy nanoparticles, which migrate and fuse from the scaffold to the surface of the cardiomyocytes, revealing a potential mechanism for restoring infarct myocardium. The incorporated Ppy nanoparticles thus significantly enhance the functionalization of the cardiomyocytes, resulting in excellent synchronous contraction by increasing the expression of α‐actinin and CX‐43. Cardiomyocytes‐loaded ECP can improve the cardiac function in myocardial‐infarction (MI) affected rat models. The results show that the fractional shortening and ejection fraction are elevated by about 50% and that the infarct size is reduced by 42.6%. Collectively, this study highlights an effective cardiac patch based on mussel‐inspired conductive particle adhesion and a superelastic cryogel promising for the restoration of infarcted myocardium.

Tumor hypoxia is the Achilles heel of oxygen-dependent photodynamic therapy (PDT), and tremendous challenges are confronted to reverse the tumor hypoxia. In this work, an oxidative phosphorylation inhibitor of atovaquone (ATO) and a photosensitizer of chlorine e6 (Ce6)-based self-delivery nanomedicine (designated as ACSN) were prepared via π–π stacking and hydrophobic interaction for O2-economized PDT against hypoxic tumors. Specifically, carrier-free ACSN exhibited an extremely high drug loading rate and avoided the excipient-induced systemic toxicity. Moreover, ACSN not only dramatically improved the solubility and stability of ATO and Ce6 but also enhanced the cellular internalization and intratumoral permeability. Abundant investigations confirmed that ACSN effectively suppressed the oxygen consumption to reverse the tumor hypoxia by inhibiting mitochondrial respiration. Benefiting from the synergistic mechanism, an enhanced PDT effect of ACSN was observed on the inhibition of tumor growth. This self-delivery system for oxygen-economized PDT might be a potential appealing clinical strategy for tumor eradication.

No abstract

No abstract

No abstract

In this study, we report a facile approach to develop an injectable hydrogel with an in situ and pH sensitive drug delivery system for cancer treatment. The hydrogel was based on modified chitosan and alginate. We conjugated doxorubicin (DOX) to succinated chitosan (S-chi) via a Schiff base between a ketone group in the DOX and an amine group in the S-chi, which led to a pH sensitive release of DOX upon the stimulus of an acidic tumor microenvironment. Hydrogel formed in minutes while DOX conjugated S-chi was mixed with oxidized alginate. The hydrogel structure was characterized by cryo-imaging, FTIR and a rheology test. The DOX release profiles were tested in response to different pH values. The MTT assay showed a low toxicity of the hydrogel. The gel in turn inhibited the growth of tumor cells MCF-7 effectively when loaded with DOX. Finally, the DOX laden hydrogel was injected into the xenograft breast tumor model and significantly inhibited tumor growth.